Metabolites

17 pages, 3970 KiB

Open AccessArticle

Rats Exposed to Excess Sucrose During a Critical Period Develop Inflammation and Express a Secretory Phenotype of Vascular Smooth Muscle Cells

by Verónica Guarner-Lans, Elizabeth Soria-Castro, Agustina Cano-Martínez, María Esther Rubio-Ruiz, Gabriela Zarco, Elizabeth Carreón-Torres, Oscar Grimaldo, Vicente Castrejón-Téllez and Israel Pérez-Torres

Metabolites 2024, 14(10), 555; https://doi.org/10.3390/metabo14100555 (registering DOI) - 17 Oct 2024

Abstract

Background: Neonatal rats that receive sucrose during a critical postnatal period (CP, days 12 to 28) develop hypertension by the time they reach adulthood. Inflammation might contribute to changes during this period and could be associated with variations in the vascular smooth muscle [...] Read more.

Background: Neonatal rats that receive sucrose during a critical postnatal period (CP, days 12 to 28) develop hypertension by the time they reach adulthood. Inflammation might contribute to changes during this period and could be associated with variations in the vascular smooth muscle (VSMC) phenotype. Objective: We studied changes in inflammatory pathways that could underlie the expression of the secretory phenotype in the VSMC in the thoracic aorta of rats that received sucrose during CP. Methods: We analyzed histological changes in the aorta and the expression of the COX-2, TLR4, iNOS, eNOS, MMP-2 and -9, and β- and α-actin, the quantities of TNF-α, IL-6, and IL-1β using ELISA, and the levels of fatty acids using gas chromatography. Results: The aortic wall presented disorganization, decellularization, and wavy elastic fibers and an increase in the lumen area. The α- and β-actin expressions were decreased, while COX-2, TLR4, TNF-α, and the activity of IL-6 were increased. Oleic acid was increased in CP in comparison to the control group. Conclusions: There is transient hypertension at the end of the CP that is accompanied by inflammation and a change in the phenotype of VSMC to the secretory phenotype. The inflammatory changes could act as epigenetic signals to determine the development of hypertension when animals reach adulthood. Full article

(This article belongs to the Special Issue Impact of Macronutrients on Metabolism)

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Flow chart for the management of the experimental animals. Full article ">Figure 2
Histological changes of the aortic rings from control rats receiving the normal diet (A,C) and rats exposed to sucrose in the drinking water during the CP (B,D). The pink-stained images were acquired from histological sections stained with HE using a bright field microscope coupled to a camera (see <a href="#sec2-metabolites-14-00555" class="html-sec">Section 2</a>). From the same sections with HE staining, images in a gray tone were acquired with the relief phase color channel for close-ups in which the differences in the structure of the aortic wall between the two groups are distinguished in more detail. In the lower-right gray image, the locations of undulations (black arrow) and aneurysms (white arrows) are indicated. On the right side of the image, the graphs of the comparison of the measurements of the thickness (E) and the total area of the wall (F), as well as the total area of the aortic lumen (G), are shown. Values represent the mean ± standard error (n = 6), * p = 0.01, *** p = 0.001 (<a href="#metabolites-14-00555-f001" class="html-fig">Figure 1</a>). Full article ">Figure 3
Immunohistochemistry for COX-2, iNOS, and eNOS in control aortas and aortas from rats that received sucrose during the CP. Panels (A,C,E) (COX-2, iNOS, and eNOS in the C group, respectively) and panels (B,D,F) (COX-2, iNOS and eNOS in the CP group, respectively). *** p < 0.001. Values represent the mean ± SE, n = 10, per group. Abbreviations: EF = elastic fibers, E = endothelium, MZ = muscular zone. Full article ">Figure 4
Immunohistochemistry for TLR4 in control aortas (A) and aortas from rats that received sucrose during the CP (B). * p < 0.03 Values represent the mean ± SE (n = 10 per group). Abbreviations: EF = elastic fibers, E = endothelium, MZ = muscular zone. Full article ">Figure 5
Concentrations of interleukins IL-1β (A), IL-6 (B), and TNF-α (C) in serum from control and CP rats.. Values represent the mean ± SE (n = 8 per group), * p < 0.05. Full article ">Figure 6
Changes in the expression of SMA (A) and β-actin (B) in thoracic aortas from C rats and CP rats. Values represent the mean ± SE (n = 8 animals per group). * p < 0.05. Representative western blot images are included in the lower panel. AU refers to arbitrary units, which are determined as the relative density of the band of the protein of interest in relation to the control of charge protein (GAPDH). Full article ">Figure 7
Changes in the expression of MMP-2 (A) and -9 (B) in thoracic aortas from control rats receiving the normal diet (C) and rats receiving sucrose during the critical period (CP). Values represent the mean ± SE, n = 8 animals per group. * p < 0.05. Representative western blot images are included in the lower panel. AU refers to arbitrary units which are determined as the relative density of the band of the protein of interest in relation to the control of charge protein (GAPDH). Full article ">Figure 8
Excess consumption of sucrose in drinking water during the CP of vessel development in rats results in transitory hypertension accompanied by a change in the phenotype of VSMCs to the secretory type. There is a decrease in smooth muscle of β- and α-actin, which could act as an epigenetic cue to determine the development of hypertension when the animals reach adulthood. This change in the phenotype might be induced by increased inflammation characterized by increased levels of TNF-α, IL-6, and an increase in the expression of COX-2, TLR-4, and MMP-9, arrow-up = increase, arrow-down= decrease. Full article ">

12 pages, 2076 KiB

Open AccessArticle

Liraglutide Therapy in Obese Patients Alters Macrophage Phenotype and Decreases Their Tumor Necrosis Factor Alpha Release and Oxidative Stress Markers—A Pilot Study

by Łukasz Bułdak, Aleksandra Bołdys, Estera Skudrzyk, Grzegorz Machnik and Bogusław Okopień

Metabolites 2024, 14(10), 554; https://doi.org/10.3390/metabo14100554 - 16 Oct 2024

Abstract

Introduction: Obesity is one of the major healthcare challenges. It affects one in eight people around the world and leads to several comorbidities, including type 2 diabetes, hyperlipidemia, and arterial hypertension. GLP-1 analogs have become major players in the therapy of obesity, [...] Read more.

Introduction: Obesity is one of the major healthcare challenges. It affects one in eight people around the world and leads to several comorbidities, including type 2 diabetes, hyperlipidemia, and arterial hypertension. GLP-1 analogs have become major players in the therapy of obesity, leading to significant weight loss in patients. However, benefits resulting from their usage seem to be greater than simple appetite reduction and glucose-lowering potential. Recent data show better cardiovascular outcomes, which are connected with the improvements in the course of atherosclerosis. Macrophages are crucial cells in the forming and progression of atherosclerotic lesions. Previously, it was shown that in vitro treatment with GLP-1 analogs can affect macrophage phenotype, but there is a paucity of in vivo data. Objective: To evaluate the influence of in vivo treatment with liraglutide on basic phenotypic and functional markers of macrophages. Methods: Basic phenotypic features were assessed (including inducible nitric oxide synthase, arginase 1 and mannose receptors), proinflammatory cytokine (IL-1β, TNFα) release, and oxidative stress markers (reactive oxygen species, malondialdehyde) in macrophages obtained prior and after 3-month therapy with liraglutide in patients with obesity. Results: Three-month treatment with subcutaneous liraglutide resulted in the alteration of macrophage phenotype toward alternative activation (M2) with accompanying reduction in the TNFα release and diminished oxidative stress markers. Conclusions: Our results show that macrophages in patients treated with GLP-1 can alter their phenotype and function. Those findings may at least partly explain the pleiotropic beneficial cardiovascular effects seen in subjects treated with GLP-1 analogs. Full article

(This article belongs to the Special Issue Lipid Metabolism and Atherosclerosis: Cell Specific Functions and Molecular Mechanism of the Disease)

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Flowchart of the study. Full article ">Figure 2
Basic phenotypical features of macrophages during the course of in vivo treatment with liraglutide and ex vivo challenge with LPS. The expression of mRNA for NOS2 (a), ARG1 (b), and MRC1 (c). Protein expression of iNOS (d), arg1 (e), and MR (f). Representative Western blots for assessment of protein expression (g). Immunofluorescent staining of macrophages for iNOS and MR (h). Bar represents 50 µm (n = 3–7). *—p < 0.05; **—p < 0.01. Abbreviations: ARG1/arg1—arginase 1; NOS2/iNOS—inducible nitric oxide; LPS—lipopolysaccharide; MRC1/MR—mannose receptor; ROS—relative optical density; RU—relative units. Full article ">Figure 3
Markers of proinflammatory response: TNFα (a) and IL-1β (b) (n = 7). *—p < 0.05; **—p < 0.01. Abbreviation: LPS—lipopolysaccharide. Full article ">Figure 4
Markers of oxidative stress: reactive oxygen species (a) and malondialdehyde (b) (n = 8). *—p < 0.05; **—p < 0.01. Abbreviation: LPS—lipopolysaccharide. Full article ">

16 pages, 2098 KiB

Open AccessArticle

Mitochondrial Abundance and Function Differ Across Muscle Within Species

by Con-Ning Yen, Jocelyn S. Bodmer, Jordan C. Wicks, Morgan D. Zumbaugh, Michael E. Persia, Tim H. Shi and David E. Gerrard

Metabolites 2024, 14(10), 553; https://doi.org/10.3390/metabo14100553 - 16 Oct 2024

Abstract

Background: Mitochondria are considered the powerhouse of cells, and skeletal muscle cells are no exception. However, information regarding muscle mitochondria from different species is limited. Methods: Different muscles from cattle, pigs and chickens were analyzed for mitochondrial DNA (mtDNA), protein and [...] Read more.

Background: Mitochondria are considered the powerhouse of cells, and skeletal muscle cells are no exception. However, information regarding muscle mitochondria from different species is limited. Methods: Different muscles from cattle, pigs and chickens were analyzed for mitochondrial DNA (mtDNA), protein and oxygen consumption. Results: Bovine oxidative muscle mitochondria contain greater mtDNA (p < 0.05), protein (succinate dehydrogenase, SDHA, p < 0.01; citrate synthase, CS, p < 0.01; complex I, CI, p < 0.05), and oxygen consumption (p < 0.01) than their glycolytic counterpart. Likewise, porcine oxidative muscle contains greater mtDNA (p < 0.01), mitochondrial proteins (SDHA, p < 0.05; CS, p < 0.001; CI, p < 0.01) and oxidative phosphorylation capacity (OXPHOS, p < 0.05) in comparison to glycolytic muscle. However, avian oxidative skeletal muscle showed no differences in absolute mtDNA, SDHA, CI, complex II, lactate dehydrogenase, or glyceraldehyde 3 phosphate dehydrogenase compared to their glycolytic counterpart. Even so, avian mitochondria isolated from oxidative muscles had greater OXPHOS capacity (p < 0.05) than glycolytic muscle. Conclusions: These data show avian mitochondria function is independent of absolute mtDNA content and protein abundance, and argue that multiple levels of inquiry are warranted to determine the wholistic role of mitochondria in skeletal muscle. Full article

(This article belongs to the Special Issue Unlocking the Mysteries of Muscle Metabolism in the Animal Sciences)

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(A,D,G) Absolute mitochondrial DNA (mtDNA) number in glycolytic and oxidative muscles. (B,E,H) Relative mtDNA compared to genomic DNA (2 −∆CT) in glycolytic and oxidative muscles. (C,F,I) Fold change (2 −∆∆CT) of mtDNA in oxidative compared to the glycolytic muscle type. (A–C) Bovine (n = 6) and (D–F) porcine (n = 6) muscle mtDNA content from longissimus lumborum (LL) and masseter (MS). (G–I) Avian muscle (n = 6) mtDNA content in pectoralis major (PM) and quadriceps femoris (QF). All values are displayed as least square means followed by standard error bars. Significance is denoted as * p < 0.05, ** p < 0.01, *** p < 0.001. Full article ">Figure 2
Oxidative protein abundance from whole muscle in bovine (A–D), porcine (E–H), and avian (I–L). Bovine (n = 6) and porcine (n = 6) muscle protein content from longissimus lumborum (LL) and masseter (MS). Avian (n = 6) muscle protein content in pectoralis major (PM) and quadriceps femoris (QF). Oxidative protein abundance of (A,E,I) succinate dehydrogenase (SDHA), (B,F,J) citrate synthase (CS), and (C,G,K) voltage-dependent anion channel (VDAC). (D,H,L) Representative Western blot images of SDHA, CS, VDAC, and total protein stain (Ponceau S). All values are displayed as least square means followed by standard error bars. Significance is denoted as * p < 0.05, ** p < 0.01, *** p < 0.001. Full article ">Figure 3
Glycolytic protein abundance from whole muscle in bovine (A–C), porcine (D–F), and avian (G–I). Bovine (n = 6) and porcine (n = 6) muscle protein content from longissimus lumborum (LL) and masseter (MS). Avian muscle (n = 6) protein content in pectoralis major (PM) and quadriceps femoris (QF). Glycolytic enzyme protein abundance of (A,D,G) glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and (B,E,H) lactate dehydrogenase (LDHA). (C,F,I) Representative Western blot images of GAPDH, LDHA, and total protein stain (Ponceau S). All values are displayed as least square means followed by standard error bars. Significance is denoted as ** p < 0.01 and *** p < 0.001. Full article ">Figure 4
Mitochondrial protein abundance in glycolytic and oxidative muscles from bovine (A–C), porcine (D–F), and avian (G–I) mitochondria enriched fractions. Bovine (n = 6) and porcine (n = 6) mitochondrial protein content from longissimus lumborum (LL) and masseter (MS) muscles. Avian (n = 6) mitochondrial protein content from pectoralis major (PM) and quadriceps femoris (QF) muscles. (A,D,G) Mitochondrial proteins abundance of complex I (CI, NDUFB8) and (B,E,H) complex II (CII, SDHB) and (C,F,I) voltage dependent anion channel (VDAC). (J) Representative Western blot images of complex I, complex II, complex III, complex V, VDAC, and total protein stain (Ponceau S). All values are displayed as least square means followed by standard error bars. Significance is denoted as † p = 0.08, * p < 0.05, ** p < 0.01. Full article ">Figure 5
Oxygen consumption rate of mitochondria isolated from (A,D) bovine (n = 6) and (B,E) porcine (n = 6) longissimus lumborum (LL) and masseter (MS) and (C,F) avian (n = 8) pectoralis major (PM) and quadriceps femoris (QF) muscles under saturating concentrations of pyruvate/malate (PyM; A–C) and succinate/rotenone (SR; D–F) substrates. Baseline represents basal respiration of isolated mitochondria with substrates. OXPHOS capacity is ADP (5 mM) stimulated respiration. Proton leak is determined with 2 µM oligomycin. Maximal respiration is achieved with the uncoupler FCCP (4 µM). All values are displayed as least square means followed by standard error bars. Significance is denoted as * p < 0.05 and ** p < 0.01. Full article ">Figure 6
Oxygen consumption rate of mitochondria isolated from (A,D) bovine (n = 6) and (B,E) porcine (n = 6) longissimus lumborum (LL) and masseter (MS) and (C,F) avian pectoralis major (PM, n = 10) and quadriceps femoris (QF, n = 9) muscles under saturating concentrations of glutamate/malate (GM; A–C) and palmitoyl-carnitine/malate (PCM; D–F) substrates. Baseline represents basal respiration of isolated mitochondria with substrates. OXPHOS capacity is ADP (5 mM) stimulated respiration. Proton leak is determined with 2 µM oligomycin. Maximal respiration is achieved with the uncoupler FCCP (4 µM). All values are displayed as least square means followed by standard error bars. Significance is denoted as * p < 0.05, ** p < 0.01, and *** p < 0.001. Full article ">

17 pages, 823 KiB

Open AccessArticle

Maternal Dietary Deficiencies in Folic Acid and Choline Change Metabolites Levels in Offspring after Ischemic Stroke

by Faizan Anwar, Mary-Tyler Mosley, Paniz Jasbi, Jinhua Chi, Haiwei Gu and Nafisa M. Jadavji

Metabolites 2024, 14(10), 552; https://doi.org/10.3390/metabo14100552 - 16 Oct 2024

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Abstract

Background/objectives: Ischemic stroke is a major health concern, and nutrition is a modifiable risk factor that can influence recovery outcomes. This study investigated the impact of maternal dietary deficiencies in folic acid (FADD) or choline (ChDD) on the metabolite profiles of offspring [...] Read more.

Background/objectives: Ischemic stroke is a major health concern, and nutrition is a modifiable risk factor that can influence recovery outcomes. This study investigated the impact of maternal dietary deficiencies in folic acid (FADD) or choline (ChDD) on the metabolite profiles of offspring after ischemic stroke. Methods: A total of 32 mice (17 males and 15 females) were used to analyze sex-specific differences in response to these deficiencies. Results: At 1-week post-stroke, female offspring from the FADD group showed the greatest number of altered metabolites, including pathways involved in cholesterol metabolism and neuroprotection. At 4 weeks post-stroke, both FADD and ChDD groups exhibited significant disruptions in metabolites linked to inflammation, oxidative stress, and neurotransmission. Conclusions: These alterations were more pronounced in females compared to males, suggesting sex-dependent responses to maternal dietary deficiencies. The practical implications of these findings suggest that ensuring adequate maternal nutrition during pregnancy may be crucial for reducing stroke susceptibility and improving post-stroke recovery in offspring. Nutritional supplementation strategies targeting folic acid and choline intake could potentially mitigate the long-term adverse effects on metabolic pathways and promote better neurological outcomes. Future research should explore these dietary interventions in clinical settings to develop comprehensive guidelines for maternal nutrition and stroke prevention. Full article

(This article belongs to the Special Issue Neuronutrition: Metabolomic Insights and Perspectives)

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16 pages, 273 KiB

Open AccessArticle

Metabolic and Immune Parameters in Pregnant Women with Impaired Glucose Metabolism—A Pilot Study

by Jelena Omazić, Andrijana Muller, Blaž Dumančić, Mirta Kadivnik, Jasna Aladrović, Lana Pađen, Kristina Kralik, Nikolina Brkić, Blaženka Dobrošević, Barbara Vuković and Jasenka Wagner

Metabolites 2024, 14(10), 551; https://doi.org/10.3390/metabo14100551 - 16 Oct 2024

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Abstract

Gestational diabetes mellitus (GDM) is a public health problem with increasing prevalence. Analyses of metabolic and immune profiles have great potential for discovering new markers and mechanisms related to the development of GDM. We monitored 61 pregnant women during the first and third [...] Read more.

Gestational diabetes mellitus (GDM) is a public health problem with increasing prevalence. Analyses of metabolic and immune profiles have great potential for discovering new markers and mechanisms related to the development of GDM. We monitored 61 pregnant women during the first and third trimesters of pregnancy, including 13 pregnant women with GDM, 14 pregnant women with elevated glucose in the first trimester and 34 healthy pregnant women. A number of metabolic and immunological parameters were measured, including glucose, insulin, lipid status, fatty acids, lymphocyte profile, adiponectin, IL-6, IL-10 and TNF-a. A higher number of T-helper lymphocytes and a higher ratio of helper/cytotoxic lymphocytes was found in the control group in the first trimester of pregnancy. Pregnant women whose glucose threshold values were measured in the first trimester, but who did not develop GDM, showed a higher percentage of neutrophils and a lower percentage of lymphocytes in the third trimester. Differences in polyunsaturated fatty acids levels were observed between healthy pregnant women and those with glucose metabolism disorders in the first trimester of pregnancy. The results of this pilot study demonstrate that there are differences in the profiles of T lymphocytes, NK cells and polyunsaturated fatty acids between the examined groups of pregnant women, which can serve as a direction for future research. Full article

(This article belongs to the Special Issue Glucose Metabolism in Pregnancy)

12 pages, 2854 KiB

Open AccessArticle

Multi-Modal Investigation of Metabolism in Murine Breast Cancer Cell Lines Using Fluorescence Lifetime Microscopy and Hyperpolarized 13C-Pyruvate Magnetic Resonance Spectroscopy

by Sarah Erickson-Bhatt, Benjamin L. Cox, Erin Macdonald, Jenu V. Chacko, Paul Begovatz, Patricia J. Keely, Suzanne M. Ponik, Kevin W. Eliceiri and Sean B. Fain

Metabolites 2024, 14(10), 550; https://doi.org/10.3390/metabo14100550 (registering DOI) - 15 Oct 2024

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Abstract

Background/Objectives: Despite the role of metabolism in breast cancer metastasis, we still cannot predict which breast tumors will progress to distal metastatic lesions or remain dormant. This work uses metabolic imaging to study breast cancer cell lines (4T1, 4T07, and 67NR) with [...] Read more.

Background/Objectives: Despite the role of metabolism in breast cancer metastasis, we still cannot predict which breast tumors will progress to distal metastatic lesions or remain dormant. This work uses metabolic imaging to study breast cancer cell lines (4T1, 4T07, and 67NR) with differing metastatic potential in a 3D collagen gel bioreactor system. Methods: Within the bioreactor, hyperpolarized magnetic resonance spectroscopy (HP-MRS) is used to image lactate/pyruvate ratios, while fluorescence lifetime imaging microscopy (FLIM) of endogenous metabolites measures metabolism at the cellular scale. Results: HP-MRS results showed no lactate peak for 67NR and a comparatively large lactate/pyruvate ratio for both 4T1 and 4T07 cell lines, suggestive of greater pyruvate utilization with greater metastatic potential. Similar patterns were observed using FLIM with significant increases in FAD intensity, redox ratio, and NAD(P)H lifetime. The lactate/pyruvate ratio was strongly correlated to NAD(P)H lifetime, consistent with the role of NADH as an electron donor for the glycolytic pathway, suggestive of an overall upregulation of metabolism (both glycolytic and oxidative), for the 4T07 and 4T1 cell lines compared to the non-metastatic 67NR cell line. Conclusions: These findings support a complementary role for HP-MRS and FLIM enabled by a novel collagen gel bioreactor system to investigate metastatic potential and cancer metabolism. Full article

(This article belongs to the Section Cell Metabolism)

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(A) The multi-modal bioreactor design uses a 3D collagen gel cell culture in the MRI-compatible bioreactor chamber with (B) a transparent portal in the base that can be placed on a fluorescence microscope stage for fluorescence lifetime imaging microscopy (FLIM setup). (C) The bioreactor system in the MRI setup adjacent to the volume coil was used for signal excitation and detection. (D) Culture media flow was constantly maintained (green arrow) with temperature control maintained by water bath flow around the culture volume (blue arrow). Hyperpolarized metabolic substrates (13C1-pyruvate in this case) were injected via bolus infusion into base of the culture chamber (red arrow). Full article ">Figure 2
(Top) Example fluorescence lifetime imaging microscopy (FLIM) images showing mean lifetime (τm) for NAD(P)H from non-metastatic (67NR), metastatically dormant (4T07), and metastatic (4T1) murine breast cancer cells (upper images). Cells were imaged at a 740 nm wavelength with a 450/70 nm filter. The color-coded images in the first row (upper images) show that the 67NR cells have a shorter τm (more yellow in color) compared to the longer τm in 4T07 and 4T1 cells (more blue in color). The cross hairs centered on specific cells in each panel indicate where fluorescence life time measurement is localized. (Bottom) Example photon lifetime distribution from a single pixel location as displayed by the SPCImage software (v8.0). Units are in nanoseconds (ns). Full article ">Figure 3
Representative spectra from the 3 cell lines studied, 4T1 (top), 4T07 (middle), and 67NR (bottom), showing the pyruvate substrate (170 ppm, truncated), pyruvate hydrate (178 ppm) and lactate (182 ppm) components of hyperpolarized [1-13C] pyruvate metabolism. A vial of urea was included adjacent to the bioreactor chamber as a reference (163 ppm) for calibration. Elevated lactate is apparent for the 4T1 (highly metastatic) in contrast to the 4T07 and 67NR (non-metastatic) cell lines. Note that the small peak near the lactate frequency for the 67NR spectra was measured to be below the noise threshold by the jMRUI analysis software (v5.2). Full article ">Figure 4
(a) An elevated lactate/pyruvate (Lac/Pyr) ratio was found for the 4T1 (highly metastatic) vs. 67NR (non-metastatic) cell lines, in contrast to (b) where the elevated redox ratio and (c) FAD intensity was found for 4T07 (metastatic-dormant) vs. both the 4T1 (highly metastatic) and 67NR (non-metastatic) cell lines. (d) NADH lifetimes trended higher for both 4T07 (metastatic-dormant) and 4T1 (highly metastatic) cell lines compared to the 67NR (non-metastatic) cell line. Three replicates were performed in parallel for each cell line, for a total of N = 9 data points per cell-line. * indicates statistical significance at p < 0.05, ** p < 0.01, *** p < 0.001, and ns stands for “not significant”. Full article ">

31 pages, 1017 KiB

Open AccessReview

Nutritional Modulation of the Gut–Brain Axis: A Comprehensive Review of Dietary Interventions in Depression and Anxiety Management

by Mariana Merino del Portillo, Vicente Javier Clemente-Suárez, Pablo Ruisoto, Manuel Jimenez, Domingo Jesús Ramos-Campo, Ana Isabel Beltran-Velasco, Ismael Martínez-Guardado, Alejandro Rubio-Zarapuz, Eduardo Navarro-Jiménez and José Francisco Tornero-Aguilera

Metabolites 2024, 14(10), 549; https://doi.org/10.3390/metabo14100549 - 14 Oct 2024

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Abstract

Mental health is an increasing topic of focus since more than 500 million people in the world suffer from depression and anxiety. In this multifactorial disorder, parameters such as inflammation, the state of the microbiota and, therefore, the patient’s nutrition are receiving more [...] Read more.

Mental health is an increasing topic of focus since more than 500 million people in the world suffer from depression and anxiety. In this multifactorial disorder, parameters such as inflammation, the state of the microbiota and, therefore, the patient’s nutrition are receiving more attention. In addition, food products are the source of many essential ingredients involved in the regulation of mental processes, including amino acids, neurotransmitters, vitamins, and others. For this reason, this narrative review was carried out with the aim of analyzing the role of nutrition in depression and anxiety disorders. To reach the review aim, a critical review was conducted utilizing both primary sources, such as scientific publications and secondary sources, such as bibliographic indexes, web pages, and databases. The search was conducted in PsychINFO, MedLine (Pubmed), Cochrane (Wiley), Embase, and CinAhl. The results show a direct relationship between what we eat and the state of our nervous system. The gut–brain axis is a complex system in which the intestinal microbiota communicates directly with our nervous system and provides it with neurotransmitters for its proper functioning. An imbalance in our microbiota due to poor nutrition will cause an inflammatory response that, if sustained over time and together with other factors, can lead to disorders such as anxiety and depression. Changes in the functions of the microbiota–gut–brain axis have been linked to several mental disorders. It is believed that the modulation of the microbiome composition may be an effective strategy for a new treatment of these disorders. Modifications in nutritional behaviors and the use of ergogenic components are presented as important non-pharmacological interventions in anxiety and depression prevention and treatment. It is desirable that the choice of nutritional and probiotic treatment in individual patients be based on the results of appropriate biochemical and microbiological tests. Full article

(This article belongs to the Special Issue Advances in Food Sciences: Metabolomics to Unravel the Complexity of Food Metabolites)

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14 pages, 771 KiB

Open AccessArticle

The Impact of Negative Energy Balance in Holstein-Friesian Cows on the Blood Concentrations of Interleukin-6 and Plasminogen

by Kalina Wnorowska, Krzysztof Młynek and Kamila Puppel

Metabolites 2024, 14(10), 548; https://doi.org/10.3390/metabo14100548 - 14 Oct 2024

Viewed by 339

Abstract

Background/Objectives: The negative energy balance activaties of spontaneous lipolysis. This may promotes inflammation within the adipose tissue. The aim of the study was to explain the development of inflammation during increased lactogenesis. It was hypothesized that lipolysis contributes synthesis of interleukin-6 and plasminogen. [...] Read more.

Background/Objectives: The negative energy balance activaties of spontaneous lipolysis. This may promotes inflammation within the adipose tissue. The aim of the study was to explain the development of inflammation during increased lactogenesis. It was hypothesized that lipolysis contributes synthesis of interleukin-6 and plasminogen. Methods: The study was in production conditions carried out using Holstein-Friesian cows. The period studied covered time of early lactation. Results: Up to the peak of lactation, milk yield strongly influenced the rate of loss of body condition. This had an impact on with the intensity of the release of the fatty acids. In both cases this relationships strengthened to the peak of production. Oobserved tendencies towards a decrease in the concentration of glucose and an increase in that of leptin. Loss of the body condition and the release of NEFA were were influencing to affect the blood concentrations of interleukin-6 and plasminogen. We have shown that IL-6 has a relatively strong correlation with the NEFA. They correlate with IL-6 independently of EB influence. This may suggest independent associations between these variables, which could potentially be applied in practice. Conclusions: The NEFA release in the long term can increase the inflammatory response within adipose tissue and can intensify the release of interleukin-6 and plasminogen. It is likely that in the initial stage of lactogenesis, the inflammatory process developing within adipose tissue is physiologically justified. Our results can provide background to this little-described area of research. Full article

(This article belongs to the Special Issue Metabolomics Studies in Ruminant Models: Unraveling Nutritional Physiology and Health)

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21 pages, 21358 KiB

Open AccessArticle

Didymin Ameliorates Dextran Sulfate Sodium (DSS)-Induced Ulcerative Colitis by Regulating Gut Microbiota and Amino Acid Metabolism in Mice

by Zhongxing Chu, Zuomin Hu, Feiyan Yang, Yaping Zhou, Yiping Tang and Feijun Luo

Metabolites 2024, 14(10), 547; https://doi.org/10.3390/metabo14100547 - 14 Oct 2024

Viewed by 376

Abstract

Background: Didymin is a dietary flavonoid derived from citrus fruits and has been shown to have extensive biological functions, especially anti-inflammatory effects, but its mechanism is unclear. The purpose of this study was to investigate the potential mechanism of didymin that alleviates ulcerative [...] Read more.

Background: Didymin is a dietary flavonoid derived from citrus fruits and has been shown to have extensive biological functions, especially anti-inflammatory effects, but its mechanism is unclear. The purpose of this study was to investigate the potential mechanism of didymin that alleviates ulcerative colitis. Methods and Results: Our results indicated that didymin could alleviate the symptoms of ulcerative colitis, as it inhibited the expressions of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Didymin also promoted the expressions of claudin-1 and zona occludens-1(ZO-1), which are closely related with restoring colon barrier function. Didymin also increased the abundance of Firmicutes and Verrucomicobiota, while decreasing the abundance of Bacteroidota and Proteobacteria. Meanwhile, didymin significantly altered the levels of metabolites related to arginine synthesis and metabolism, and lysine degradation in the colitis mice. Utilizing network pharmacology and molecular docking, our results showed that the metabolites L-ornithine and saccharin could interact with signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa-B (NF-κB). In this in vitro study, L-ornithine could reduce the expressions of transcription factors STAT3 and NF-κB, and it also inhibited the expressions of IL-6 and IL-1β in the lipopolysaccharides (LPS) induced in RAW264.7 cells, while saccharin had the opposite effect. Conclusions: Taken together, didymin can regulate gut microbiota and alter metabolite products, which can modulate STAT3 and NF-κB pathways and inhibit the expressions of inflammatory factors and inflammatory response in the DSS-induced colitis mice. Full article

(This article belongs to the Special Issue Targeting Microbiota and Metabolites for Prevention and Treatment of Human Diseases)

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Effect of DID supplementation on the symptoms of DSS-induced UC in mice. (A) Animal treatments schedule. (B) Bleeding in the colon at the end of the experiment. (C) Percentage of the body-weight change during the experiment. (D) DAI score. (E) Representative image of the colon in different groups and the colon length. Data are presented as means ± SEM, n = 10. (F) Representative H&E-stained sections of colonic tissue (20× magnification). (G) Inflammation and (H) intestinal barrier were analyzed by Western blot. Data are presented as means ± SEM, n = 3. Data are presented as means ± SEM, n = 10. # p < 0.05 and ## p < 0.01 versus the CON group; * p < 0.05 and ** p < 0.01 versus the DID group. Full article ">Figure 2
Effects of DID supplementation on the change in the gut microbiota. (A) Pan analysis curve. (B) Core analysis curve. (C) Chao index. (D) Shannon index. (E) PCoA analysis on OTU level. (F) Relative abundances of the gut microbiota at the phylum level. (G) Relative abundances of the gut microbiota at the family level. (H) Relative abundances of the gut microbiota at the genus level. (I) LEfSe multi-level species hierarchical tree diagram, using different colors to represent certain enriched taxa. Data are presented as means ± SEM, n = 6. # p < 0.05 and ## p < 0.01 versus the CON group; * p < 0.05 versus the DID group and ns: there was no significant difference. Full article ">Figure 3
(A) Principal component analysis (PCA) of metabolites. (B) Volcano plots of DID vs. DSS. (C) Volcano plots of DSS vs. CON. (D) Heatmap of the metabolites in the CON group altered by DSS responding to DID treatment. (E) KEGG pathway enrichment analysis. (F) Human Metabolome Database (HMDB) classification. Data are presented as means ± SEM, n = 6. Full article ">Figure 4
Spearman correlation between gut microbiota and metabolites. * p < 0.05, ** p < 0.01 and *** p < 0.001. Full article ">Figure 5
Network pharmacological analysis diagram. (A,B) Venn diagram analysis of targets of L-ornithine and saccharin with inflammation. (C,D) Targets of L-ornithine and saccharin targeting inflammation sorted by degree. (E) GO analysis of targets of L-ornithine targeting inflammation. (F) GO analysis of targets of saccharin targeting inflammation. (G) KEGG pathway analysis of targets of L-ornithine targeting inflammation. (H) KEGG pathway analysis of targets of saccharin targeting inflammation. Full article ">Figure 6
Results of molecular docking. (A,B) The complex formed by L-ornithine, saccharin and STAT3. (C,D) The complex formed by L-ornithine, saccharin and NF-κB. Full article ">Figure 7
Effects of saccharin and L-ornithine on RAW 264.7 cell viability and LPS-induced inflammatory factor expression. (A) Morphological information of RAW 264.7 cells. (B,C) Cell viability (%). (D) Inflammatory factor expressions were analyzed by Western blot. Data are presented as means ± SEM, n = 3. ## p < 0.01 versus the CON group; ** p < 0.01 versus the ORN group. Full article ">

20 pages, 2238 KiB

Open AccessArticle

Detection and Validation of Organic Metabolites in Urine for Clear Cell Renal Cell Carcinoma Diagnosis

by Kiana L. Holbrook, George E. Quaye, Elizabeth Noriega Landa, Xiaogang Su, Qin Gao, Heinric Williams, Ryan Young, Sabur Badmos, Ahsan Habib, Angelica A. Chacon and Wen-Yee Lee

Metabolites 2024, 14(10), 546; https://doi.org/10.3390/metabo14100546 - 13 Oct 2024

Viewed by 455

Abstract

Background: Clear cell renal cell carcinoma (ccRCC) comprises the majority, approximately 70–80%, of renal cancer cases and often remains asymptomatic until incidentally detected during unrelated abdominal imaging or at advanced stages. Currently, standardized screening tests for renal cancer are lacking, which presents challenges [...] Read more.

Background: Clear cell renal cell carcinoma (ccRCC) comprises the majority, approximately 70–80%, of renal cancer cases and often remains asymptomatic until incidentally detected during unrelated abdominal imaging or at advanced stages. Currently, standardized screening tests for renal cancer are lacking, which presents challenges in disease management and improving patient outcomes. This study aimed to identify ccRCC-specific volatile organic compounds (VOCs) in the urine of ccRCC-positive patients and develop a urinary VOC-based diagnostic model. Methods: This study involved 233 pretreatment ccRCC patients and 43 healthy individuals. VOC analysis utilized stir-bar sorptive extraction coupled with thermal desorption gas chromatography/mass spectrometry (SBSE-TD-GC/MS). A ccRCC diagnostic model was established via logistic regression, trained on 163 ccRCC cases versus 31 controls, and validated with 70 ccRCC cases versus 12 controls, resulting in a ccRCC diagnostic model involving 24 VOC markers. Results: The findings demonstrated promising diagnostic efficacy, with an Area Under the Curve (AUC) of 0.94, 86% sensitivity, and 92% specificity. Conclusions: This study highlights the feasibility of using urine as a reliable biospecimen for identifying VOC biomarkers in ccRCC. While further validation in larger cohorts is necessary, this study’s capability to differentiate between ccRCC and control groups, despite sample size limitations, holds significant promise. Full article

(This article belongs to the Special Issue Emerging Applications of Urinary Metabolomics in Cancer)

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The partitioned total patient population used within training and testing cohorts to generate selected VOCs for diagnostic prediction of ccRCC. Full article ">Figure 2
Partial least squares discriminant analysis plot (PLS-DA) comparing the urinary VOCs detected in ccRCC and healthy control cohorts. Full article ">Figure 3
Heat map of significant VOCs in clear cell renal cell carcinoma (ccRCC) vs. controls samples by Wilcoxon test (p < 0.05). 56 VOCs were predominant in the cancer group urine samples and 227 VOCs were elevated in the controls. The correlation between VOCs and patients ranges from low (red) to high (blue). Full article ">Figure 4
(A) The ROC curve for VOC ccRCC diagnosis logistic model verified in the training group with 194 patients (163 ccRCC vs. 31 healthy control). (B) The ROC curve for VOC ccRCC diagnosis logistic model validated in the testing group with 82 patients (70 ccRCC vs. 12 healthy control). Full article ">Figure 5
Visual representation of 23 biological pathways generated from the 283 significant VOCs found in the training cohort by Wilcoxon rank-sum test with p < 0.05. Full article ">

24 pages, 1102 KiB

Open AccessReview

Recent Advances in Metabolomics and Lipidomics Studies in Human and Animal Models of Multiple Sclerosis

by Petros Pousinis, Olga Begou, Marina Kleopatra Boziki, Nikolaos Grigoriadis, Georgios Theodoridis and Helen Gika

Metabolites 2024, 14(10), 545; https://doi.org/10.3390/metabo14100545 - 13 Oct 2024

Viewed by 477

Abstract

Multiple sclerosis (MS) is a neurodegenerative and inflammatory disease of the central nervous system (CNS) that leads to a loss of myelin. There are three main types of MS: relapsing-remitting MS (RRMS) and primary and secondary progressive disease (PPMS, SPMS). The differentiation in [...] Read more.

Multiple sclerosis (MS) is a neurodegenerative and inflammatory disease of the central nervous system (CNS) that leads to a loss of myelin. There are three main types of MS: relapsing-remitting MS (RRMS) and primary and secondary progressive disease (PPMS, SPMS). The differentiation in the pathogenesis of these two latter courses is still unclear. The underlying mechanisms of MS are yet to be elucidated, and the treatment relies on immune-modifying agents. Recently, lipidomics and metabolomics studies using human biofluids, mainly plasma and cerebrospinal fluid (CSF), have suggested an important role of lipids and metabolites in the pathophysiology of MS. In this review, the results from studies on metabolomics and lipidomics analyses performed on biological samples of MS patients and MS-like animal models are presented and analyzed. Based on the collected findings, the biochemical pathways in human and animal cohorts involved were investigated and biological mechanisms and the potential role they have in MS are discussed. Limitations and challenges of metabolomics and lipidomics approaches are presented while concluding that metabolomics and lipidomics may provide a more holistic approach and provide biomarkers for early diagnosis of MS disease. Full article

(This article belongs to the Section Endocrinology and Clinical Metabolic Research)

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Metabolic pathway analysis in biological samples (brain, CSF, plasma, serum, urine, tears) of 31 human (RRMS, CIS, PPMS, SPMS) studies. The size of the circle corresponds to the pathway impact score (x-axis). Darker circle colors indicate more significant changes (y-axis) in metabolites in the corresponding pathway. Significant metabolic pathways (p < 0.05) are numbered in decreasing order (i.e., pathway 1 being most significant to pathway 16 being least significant). Full article ">Figure 2
Dysregulated metabolic pathways in human samples, comparing different MS disease forms with healthy controls. (A) Intersection analysis of metabolic pathways dysregulated among progressive MS (PPMS, SPMS) and RRMS group human plasma samples. On the left are the significantly altered pathways in progressive MS vs. controls, on the right are all the significantly altered pathways in RRMS vs. controls, and the middle intersection is the common pathway (glycerophospholipid metabolism) among progressive and RMMS vs. control human plasma samples. (B) Intersection analysis of metabolic pathways among progressive MS (PPMS, SPMS) and RRMS group human CSF samples. On the left are all the altered pathways in progressive vs. control CSF samples, on the right are all the altered pathways in RRMS vs. control CSF samples, and the middle intersection is the common pathway (sphingolipid metabolism) among progressive and RMMS vs. control human CSF samples. (C) Intersection analysis of metabolic pathways among human plasma and CSF samples. On the left are all the altered pathways in combined progressive and RRMS vs. control plasma samples, on the right are all the altered pathways in combined progressive and RRMS vs. control CSF samples, and the middle intersection is the altered pathway in common (tryptophan metabolism) among human plasma and CSF samples. Full article ">Figure 3
Metabolic pathway analysis in biological samples (brain and plasma) of 6 mouse models of CNS demyelination studies. The size of the circle corresponds to the pathway impact score (x-axis). Darker circle colors indicate more significant changes (y-axis) in metabolites in the corresponding pathway. Significant metabolic pathways (p < 0.05) are numbered in decreasing order (i.e., pathway 1 being most significant to pathway 6 being least significant). Full article ">

24 pages, 3004 KiB

Open AccessReview

Non/Low-Caloric Artificial Sweeteners and Gut Microbiome: From Perturbed Species to Mechanisms

by Jiahao Feng, Jingya Peng, Yun-Chung Hsiao, Chih-Wei Liu, Yifei Yang, Haoduo Zhao, Taylor Teitelbaum, Xueying Wang and Kun Lu

Metabolites 2024, 14(10), 544; https://doi.org/10.3390/metabo14100544 (registering DOI) - 11 Oct 2024

Viewed by 498

Abstract

Background: Non/low-caloric artificial sweeteners (NAS) are recognized as chemical additives substituting sugars to avoid caloric intake and subsequent sugar-derived diseases such as diabetes and hyperglycemia. Six NAS have been claimed safe and are authorized by the US Food and Drug Administration (FDA) for [...] Read more.

Background: Non/low-caloric artificial sweeteners (NAS) are recognized as chemical additives substituting sugars to avoid caloric intake and subsequent sugar-derived diseases such as diabetes and hyperglycemia. Six NAS have been claimed safe and are authorized by the US Food and Drug Administration (FDA) for public use, with acceptable daily intake information available: aspartame, acesulfame-K, saccharin, sucralose, neotame, and advantame. However, the impacts of NAS on the gut microbiome have raised potential concerns, since sporadic research revealed NAS-induced microbial changes in the gastrointestinal tracts and alterations in the microbiome–host interactive metabolism. Methods: Given the fact that the gut microbiome influences kaleidoscopic physiological functions in host health, this review aimed to decipher the impacts of NAS on the gut microbiome by implementing a comprehensive two-stage literature analysis based on each NAS. Results: This review documented disturbed microbiomes due to NAS exposure to a maximal resolution of species level using taxonomic clustering analysis, and recorded metabolism alterations involved in gut microbiome–host interactions. Conclusions: The results elucidated that specific NAS exhibited discrepant impacts on the gut microbiome, even though overlapping on the genera and species were identified. Some NAS caused glucose tolerance impairment in the host, but the key metabolites and their underlying mechanisms were different. Furthermore, this review embodied the challenges and future directions of current NAS–gut microbiome research to inspire advanced examination of the NAS exposure–gut microbiome–host metabolism axis. Full article

(This article belongs to the Special Issue Effects of Environmental Exposure on Host and Microbial Metabolism)

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16 pages, 4025 KiB

Open AccessArticle

Effects of Pollen Germination and Pollen Tube Growth under Different Temperature Stresses in Mango (Mangifera indica L.) by Metabolome

by Xinyu Liu, Lirong Zhou, Chengxun Du, Songbiao Wang, Hongjin Chen, Wentian Xu, Zhuanying Yang and Qingzhi Liang

Metabolites 2024, 14(10), 543; https://doi.org/10.3390/metabo14100543 - 11 Oct 2024

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Abstract

Background: The dramatic temperature fluctuations spurred by global warming and the accompanying extreme weather events inhibit mango growth and threaten mango productivity. Particularly, mango flowering is highly sensitive to temperature changes. The mango fruit setting rate was significantly positively correlated with pollen activity, [...] Read more.

Background: The dramatic temperature fluctuations spurred by global warming and the accompanying extreme weather events inhibit mango growth and threaten mango productivity. Particularly, mango flowering is highly sensitive to temperature changes. The mango fruit setting rate was significantly positively correlated with pollen activity, and pollen activity was regulated by different metabolites. Methods: In this study, the in vitro pollen of two mango varieties (‘Renong No.1’ and ‘Jinhuang’), in which sensitivity to temperature differed significantly, were subjected to different temperature stresses (15 °C, 25 °C and 35 °C), and their metabolomics were analyzed. Results: The present results showed that 775 differential metabolites were screened by liquid chromatography–mass spectrometry and divided into 12 categories. The two varieties had significant differences in metabolite expression under different temperature stresses and the effect of low temperature on ‘Renong No.1’ mainly focused on amino acid metabolism, while the effect on ‘Jinhuang’ was mainly related to glycolysis. However, under the 35 °C temperature stress, ‘Renong No.1’ responded by redistributing riboflavin and betaine in vivo and the most obvious metabolic pathway of ‘Jinhuang’ enrichment was pyrimidine metabolism, which had undergone complex main body formation and extensive regulatory processes. The changes of metabolites of different varieties under low temperature and high temperature stress were different. Among them, flavonoids or flavonoid derivatives were included in class A (216 metabolites), C (163 metabolites) and D (233 metabolites) metabolites, indicating that flavonoid metabolites had an obvious regulatory effect on mango pollen metabolism under different temperature stress. Conclusions: The present results provide valuable information for reproductive biology studies and breeding in mango, in particular, the selection and breeding of the most suitable varieties for different production areas. Full article

(This article belongs to the Section Plant Metabolism)

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26 pages, 973 KiB

Open AccessSystematic Review

Impact of Acupuncture on Human Metabolomic Profiles: A Systematic Review

by Hongjin Li, Hannah Choi, Madelyn C. Houser, Changwei Li, Tingting Liu, Shuang Gao, Katy Sullivan and Judith M. Schlaeger

Metabolites 2024, 14(10), 542; https://doi.org/10.3390/metabo14100542 - 11 Oct 2024

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Abstract

Background/Objectives: Metabolomics provides insights into the biological underpinnings of disease development and treatment. This systematic review investigated the impact of acupuncture on metabolite levels and associated metabolic pathways using a metabolomic approach. Methods: Five databases (i.e., PubMed, Embase, Scopus, CINAHL, and Cochrane Central) [...] Read more.

Background/Objectives: Metabolomics provides insights into the biological underpinnings of disease development and treatment. This systematic review investigated the impact of acupuncture on metabolite levels and associated metabolic pathways using a metabolomic approach. Methods: Five databases (i.e., PubMed, Embase, Scopus, CINAHL, and Cochrane Central) were searched using terms such as “acupuncture” and “metabolites” to retrieve relevant journal articles published through January 2024. Studies utilizing mass spectrometry or nuclear magnetic resonance were included. Risk of bias was evaluated using the Cochrane Risk of Bias tool and the Newcastle–Ottawa scale. Metabolic pathway analysis was conducted using MetaboAnalyst 6.0 to identify common significant pathways affected by acupuncture. Additionally, subgroup pathway enrichment analysis identified metabolites significantly altered in more than two studies. Results: Among 4019 articles, 22 studies met inclusion criteria, examining changes in metabolomic biomarkers before and after acupuncture for various diseases and symptoms. A total of 226 metabolites showed significant changes, with 14 common metabolites altered in more than two studies (glutamine, androsterone glucuronide, choline, citric acid, decanoylcarnitine, estrone, glutathione, glycine, hypoxanthine, lactic acid, pyruvic acid, serine, proline, and sn-glycero-3-phosphocholine). Common pathways affected by acupuncture were glycine, serine, and threonine metabolism, glutathione metabolism, arginine biosynthesis, and glyoxylate and dicarboxylate metabolism. Conclusions: This review provides insights of the metabolomic mechanisms underlying acupuncture, highlighting its impact on specific metabolic pathways. Recognizing these changes can enhance acupuncture’s effectiveness and support the development of personalized treatments. The findings underscore metabolomics as a valuable tool for understanding and optimizing acupuncture for various diseases and symptoms. Full article

(This article belongs to the Section Endocrinology and Clinical Metabolic Research)

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14 pages, 1263 KiB

Open AccessArticle

Blackcurrant Anthocyanins Attenuate Estrogen -Deficiency-Induced Bone Loss through Modulating Microbial-Derived Short-Chain Carboxylic Acids and Phytoestrogen Metabolites in Peri- and Early Postmenopausal Women

by Briana M. Nosal, Staci N. Thornton, Alexey V. Melnik, Ali Lotfi, Manije Darooghegi Mofrad, Alexander Aksenov, Elaine Choung-Hee Lee and Ock K. Chun

Metabolites 2024, 14(10), 541; https://doi.org/10.3390/metabo14100541 - 11 Oct 2024

Viewed by 403

Abstract

Objectives: The present study aimed to assess the effects of blackcurrant (BC) anthocyanins on concentrations of microbial-derived short-chain carboxylic acids (SCCAs) and metabolites of phytoestrogens. We then examined their associations with six-month changes in whole-body bone mineral density (BMD) and biomarkers of bone [...] Read more.

Objectives: The present study aimed to assess the effects of blackcurrant (BC) anthocyanins on concentrations of microbial-derived short-chain carboxylic acids (SCCAs) and metabolites of phytoestrogens. We then examined their associations with six-month changes in whole-body bone mineral density (BMD) and biomarkers of bone metabolism. Methods: Fecal and blood samples from a pilot randomized controlled trial were collected and analyzed from 37 eligible peri- and early postmenopausal women aged 45–60 years who were randomized into one of three treatment groups consuming one placebo capsule (control), 392 mg BC (low BC) or 784 mg BC (high BC) daily for six months. Results: Significant differences were observed between groups at baseline in acetic, propionic, valeric, caproic and heptanoic acids (p < 0.05). Isobutyric acid significantly decreased from baseline (0 months) to six months in the control group (p < 0.05) and the high BC group had a significantly greater concentration than the control group at six months (p < 0.05). Butyric acid was significantly greater in the high BC group than low BC at six months (p < 0.05). Six-month changes in caproic and isobutyric acids showed weak correlations with changes in whole-body BMD (r = 0.3519, p < 0.05 and r = 0.3465, p < 0.05, respectively). Isovaleric and valeric acids displayed weak correlations with BALP (r = 0.3361, p < 0.05) and OPG (r = 0.3593, p < 0.05), respectively. Enterodiol was positively correlated with BALP (r = 0.6056, p < 0.01) while enterolactone was positively correlated with osteocalcin (r = 0.5902, p < 0.001) and negatively correlated with sclerostin (r = −0.3485, p < 0.05). Conclusions: The results suggest that BC may be a potential dietary agent to reduce postmenopausal bone loss through modulating microbially-derived SCCAs and phytoestrogen metabolites. Full article

(This article belongs to the Section Endocrinology and Clinical Metabolic Research)

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18 pages, 351 KiB

Open AccessArticle

The Assessment of Anthropometric Measures and Changes in Selected Biochemical Parameters in Obese Children in Relation to Blood Lead Level

by Katarzyna Pozorska, Irena Baranowska-Bosiacka, Dominika Raducha, Patrycja Kupnicka, Mateusz Bosiacki, Beata Bosiacka, Justyna Szmit-Domagalska, Joanna Ratajczak, Anita Horodnicka-Józwa, Mieczysław Walczak, Dariusz Chlubek and Elżbieta Petriczko

Metabolites 2024, 14(10), 540; https://doi.org/10.3390/metabo14100540 - 9 Oct 2024

Viewed by 376

Abstract

Background: Our paper draws attention to the impact of lead (Pb) on the specificity of obesity development in children exposed to environmental pollution. An advantage of this paper is the homogeneous study group comprising children of identical age from a single geographic region. [...] Read more.

Background: Our paper draws attention to the impact of lead (Pb) on the specificity of obesity development in children exposed to environmental pollution. An advantage of this paper is the homogeneous study group comprising children of identical age from a single geographic region. Moreover, while the influence of environmental toxins on adults has been extensively explored, this study delves into pediatric populations, which have yet to receive comprehensive scrutiny within the scientific literature. Methods: Initially, a group of 136 obese children (the research program lasted three consecutive years: 2016, 2017, and 2018) living in the north-western region of Poland, from whom biochemical tests and auxological data were obtained, were enrolled for analysis. Blood lead levels (BLLs) were determined in 115 children. The age of the children ranged from 7.1 to 10.4 years. The body mass index (BMI) of children averaged 21.5 ± 2.2. Results: The results showed that a large proportion of the participants had BLLs above the threshold for Pb. BLLs ≤ 5 µg/dL (considered safe for children and pregnant women) were found in over 70% of the participants, with BLLs in the range of 5.01–10.00 µg/dL in over 26% of the children, and concentrations > 10 µg/dL (considered toxic threshold for adults) in nearly 2% of the children. The results of our research revealed a positive association between BLLs and average systolic and diastolic blood pressure in the studied children. Moreover, we found a negative correlation between BLLs and absolute fat tissue content and triglyceride concentration. Among the included biochemical factors, only insulin demonstrated a statistically significant relationship with fat mass. This result suggests that early carbohydrate metabolism disorders in overweight children involve decreased peripheral tissue insulin sensitivity. Conclusions: Lead exposure may significantly contribute to the development of hypertension, insulin resistance, and glucose metabolism disorders in overweight and obese children. It is essential to implement multidirectional actions to increase awareness of the harmful effects of xenobiotic exposure, including lead, in order to prevent early-life exposure. Full article

(This article belongs to the Section Endocrinology and Clinical Metabolic Research)

18 pages, 7282 KiB

Open AccessArticle

Untargeted Metabolite Profiling Reveals Acute Toxicity of Pentosidine on Adipose Tissue of Rats

by Chuanqin Hu, Zhenzhen Shao, Wei Wu and Jing Wang

Metabolites 2024, 14(10), 539; https://doi.org/10.3390/metabo14100539 - 9 Oct 2024

Viewed by 383

Abstract

Background: Pentosidine is an advanced glycation end product that is commonly found in heat-processed foods. Pentosidine has been involved in the occurrence and development of some chronic diseases. It was reported that pentosidine exposure can impair the function of the liver and [...] Read more.

Background: Pentosidine is an advanced glycation end product that is commonly found in heat-processed foods. Pentosidine has been involved in the occurrence and development of some chronic diseases. It was reported that pentosidine exposure can impair the function of the liver and kidneys. Adipose tissue, as an active endocrine organ, plays an important role in maintaining the normal physiological function of cells. However, the metabolic mechanism that causes pentosidine to induce toxicity in adipose tissue remains unclear. Methods: In the study, thirty male Sprague-Dawley rats were divided into a normal diet group, low dose group, and high dose group. A non-targeted metabolomics approach was used to compare the metabolic profiles of adipose tissue between the pentosidine and normal diet groups. Furthermore, histopathological observation and body weight change analysis were performed to test the results of the metabolomics analysis. Results: A total of forty-two differential metabolites were identified. Pentosidine mainly disturbed twelve metabolic pathways, such as ascorbate and aldarate metabolism, glycine, serine, and threonine metabolism, sulfur metabolism, pyruvate metabolism, etc. Additionally, pyruvic acid was identified as a possible key upregulated metabolite involved in thirty-four metabolic pathways. α-Ketoglutaric acid was named as a probable key downregulated metabolite involved in nineteen metabolic pathways based on enrichment network analysis. In addition, histopathological analysis and body weight changes confirmed the results of the metabolomics analysis. Conclusions: These results provided a new perspective for the molecular mechanisms of adipose tissue toxicity induced by pentosidine. Full article

(This article belongs to the Special Issue Metabolomic Technology in Quality and Safety of Agricultural Products and Foods)

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Weight changes in rats in ND, LD, and HD groups. Data were expressed as mean ± standard deviation (SD). Differences in different groups were evaluated by t-test, “*” represents p < 0.05, “**” represents p < 0.01. ND group: normal diet group, n = 10; LD group: low dose group, n = 10; HD group: high dose group, n = 10. Full article ">Figure 2
H&E staining images of adipose tissue from ND, LD, and HD groups (original magnification: 400×). Black arrows: damaged cell membranes; barred arrows: distorted cell contours; doubleheaded arrows: blurred cell contours; dashed arrows: inflammatory cell. ND: normal diet group; LD: low dose group; HD: high dose group. Full article ">Figure 3
Multivariate statistical analysis of results from GC−MS analysis. (A) PCA score plot analysis (R2X =74.2%, Q2 = 49.9%); (B) PLS−DA score plot analysis (R2X = 81.9%, R2Y = 99.4%, Q2 = 92.8%); (C) permutation plot for PLS−DA model (n = 999), R2 = (0.0, 0.253), Q2 = (0.0, − 0.177). PCA: principal component analysis; PLS−DA: partial least squares discriminant analysis; ND: normal diet group, n = 10; LD: low dose group, n = 10; HD: high dose group, n = 10; QC: quality control. Full article ">Figure 4
Boxplots of differential metabolites in adipose tissue of rats in ND, LD, and HD groups. Differences in different groups were evaluated by Mann–Whitney U test. “*” means p < 0.05, “**” means p < 0.01, “***” means p < 0.001. ND group: normal diet group, n = 10; LD group: low dose group, n = 10; HD group: high dose group, n = 10. Full article ">Figure 5
Disturbed pathways in adipose tissue of rats from ND, LD, and HD groups. Node color in pathway analysis represented its p-value; node radius reflected their pathway impact values. (1) Ascorbate and aldarate metabolism, (2) glycine, serine, and threonine metabolism, (3) sulfur metabolism, (4) pyruvate metabolism, (5) aminoacyl−tRNA biosynthesis, (6) alanine, aspartate, and glutamate metabolism, (7) glyoxylate and dicarboxylate metabolism, (8) citrate cycle (TCA cycle), (9) glycolysis/gluconeogenesis, (10) inositol phosphate metabolism, (11) cysteine and methionine metabolism, (12) pentose and glucuronate interconversions. ND group: normal diet group, n = 10; LD group: low dose group, n = 10; HD group: high dose group, n = 10. Full article ">Figure 6
Pathway mapping of differential metabolites detected in HD group compared to ND group. Metabolic pathway generated through MetaMapp and drawn by Cytoscape. The depicted network reveals that red nodes represent significantly upregulated metabolites, blue nodes show remarkably downregulated metabolites, and gray nodes reveal no significant changes in metabolites. Size of node is positively correlated with fold change between HD group and ND group. ND group: normal diet group, n = 10; LD group: low dose group, n = 10; HD group: high dose group. Full article ">Figure 7
Network analysis of differential metabolites and metabolic pathways in pentosidine-exposed groups shows that there are forty-two differential metabolites. “*” represents p < 0.05, “**” represents p < 0.01, “***” represents p < 0.001. The red circles and black circles show upregulated and downregulated metabolites, respectively. Intensity of colors indicates fold changes in metabolites. A total of seventy-two metabolic pathways are classified as eight metabolic pathways (<a href="#app1-metabolites-14-00539" class="html-app">Table S3</a>) and connected to different metabolites by the red line (upregulated) and black line (downregulated). Full article ">Figure 8
Interplay between differential metabolites in HD group compared to ND group. Metabolic pathways are illustrated based on information obtained from KEGG database. Red boxes represent increased metabolites, blue boxes show decreased metabolites, blank boxes reveal no significant changes in metabolites. Numbers 1 to 12 represent metabolic pathways with impact value larger than 0.1 (<a href="#metabolites-14-00539-f005" class="html-fig">Figure 5</a>). ND group: normal diet group, n = 10; LD group: low dose group, n = 10; HD group: high dose group, n = 10. Full article ">

18 pages, 1875 KiB

Open AccessArticle

Wheat Peptides as Catalysts for Athletic Performance Improvement in Cross-Country Skiers: A Randomized Controlled Trial

by Mai Xiang, Qi Han, Yue Chen, Shenglin Duan, Xiaofeng Han, Xuemei Sui, Chaoxue Ren and Qirong Wang

Metabolites 2024, 14(10), 538; https://doi.org/10.3390/metabo14100538 - 7 Oct 2024

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Abstract

Objectives: This study investigated the efficacy of wheat peptide supplementation compared to regular proteins in elite cross-country skiers, providing insights into the metabolic and performance effects of these supplements in order to guide athletes in selecting optimal energy sources for training and competition. [...] Read more.

Objectives: This study investigated the efficacy of wheat peptide supplementation compared to regular proteins in elite cross-country skiers, providing insights into the metabolic and performance effects of these supplements in order to guide athletes in selecting optimal energy sources for training and competition. Methods: Nineteen healthy male cross-country skiers were enrolled and assigned to either the peptide group (PEP, n = 9) or the protein group (PRO, n = 10). A four-week intervention study involving supplementation with wheat peptides/regular proteins was conducted, and pre- and post-intervention assessments were performed to evaluate exercise capacity and metabolic profiles. Results: The study found that the PEP group and the PRO group showed distinct within-group effects on exercise performance. The PEP group demonstrated improved aerobic capacity, including better performance in 10 km roller skating, an increased lactate threshold, and reduced resting blood lactate levels. The PRO group enhanced anaerobic capacity, such as improved sprint time, hexagon test performance, and lactate clearance. Metabolomic analysis revealed specific metabolic pathways affected in each group, with the PEP group showing impacts on the α-linolenic acid pathway and the PRO group on ketone body synthesis and degradation as well as vitamin B6 metabolism. Conclusions: Our findings indicate that wheat oligopeptides and regular proteins have comparable effects on exercise performance. However, the wheat peptides may offer greater advantages in enhancing aerobic capacity. No significant variations were observed in blood metabolite profiles between the two groups, but distinct metabolic pathways exhibited different responses. Full article

(This article belongs to the Special Issue Nutrition and Supplements Intervening on Exercise Ability and Metabolism)

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General experimental design. Full article ">Figure 2
Comparative analysis of (A) blood lactate concentration levels, (B) heart rate during tests of aerobic capacity, and (C) blood lactate levels during tests of anaerobic capacity at baseline and following intervention for cross-country skiers supplemented with either wheat peptide bars or regular protein bars. Data are presented as mean ±SD. Significant differences between groups post-intervention (b p < 0.05), within the PRO group (c p < 0.05), and within the PEP group (d p < 0.05). Full article ">Figure 3
The PCA and OPLS-DA score plots. (A) PCA score plots compare the PEP and PRO groups at baseline (left) and post-intervention (right); (B) PCA score plots compare the different timepoints of baseline and post-intervention within the PEP group (left) and PRO group (right); (C) OPLS-DA score plots compare the different timepoints of baseline and post-intervention within the PEP group (left) and PRO group (right). The plots show the distribution of samples from the two groups based on principal component analysis (PCA) and/or Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA). Each point represents an individual sample, and the positioning of the points reflects their similarity or dissimilarity in terms of metabolite profiles. Full article ">Figure 4
Volcano plots and differential metabolite classes in (A) PEP group; (B) PRO group. The x-axis represents log2(fold change), while the y-axis represents false discovery rate on a -log10 scale. Full article ">Figure 5
Pathway analysis overview of metabolic pathways in the PEP and PRO groups. The circles represent the involved pathways, and significantly changed pathways are labeled with names. Full article ">Figure 6
Illustration summarizing the described factors contributing to the improved aerobic and anaerobic capacities of cross-country skiers following supplementation with wheat peptide or regular protein bars. Full article ">

20 pages, 662 KiB

Open AccessReview

Hydrogen-Rich Water to Enhance Exercise Performance: A Review of Effects and Mechanisms

by Qiaorui Zhou, Huixin Li, Ye Zhang, Yirui Zhao, Can Wang and Chang Liu

Metabolites 2024, 14(10), 537; https://doi.org/10.3390/metabo14100537 - 7 Oct 2024

Viewed by 604

Abstract

Background: Hydrogen-rich water (HRW) has garnered significant interest within the sports and exercise science community due to its selective antioxidant properties. Despite its potential benefits, comprehensive reviews specifically addressing its effects on athletic performance are limited. This review aims to assess the [...] Read more.

Background: Hydrogen-rich water (HRW) has garnered significant interest within the sports and exercise science community due to its selective antioxidant properties. Despite its potential benefits, comprehensive reviews specifically addressing its effects on athletic performance are limited. This review aims to assess the impact of HRW on sports performance and explore the underlying molecular biological mechanisms, with the goal of elucidating how HRW might enhance athletic performance. Methods: This review synthesizes research on HRW by examining articles published between 1980 and April 2024 in databases such as PubMed, the Cochrane Library, Embase, Scopus, and Web of Science. Results: It highlights HRW’s effects on various aspects of athletic performance, including endurance, strength, sprint times, lunge movements, countermovement jump height, and time to exhaustion. While the precise mechanisms by which HRW affects athletic performance remain unclear, this review investigates its general molecular biological mechanisms beyond the specific context of sports. This provides a theoretical foundation for future research aimed at understanding how HRW can enhance athletic performance. HRW targets the harmful reactive oxygen and nitrogen species produced during intense exercise, thereby reducing oxidative stress—a critical factor in muscle fatigue, inflammation, and diminished athletic performance. HRW helps to scavenge hydroxyl radicals and peroxynitrite, regulate antioxidant enzymes, mitigate lipid peroxidation, reduce inflammation, protect against mitochondrial dysfunction, and modulate cellular signaling pathways. Conclusions: In summary, while a few studies have indicated that HRW may not produce significant beneficial effects, the majority of research supports the conclusion that HRW may enhance athletic performance across various sports. The potential mechanisms underlying these benefits are thought to involve HRW’s role as a selective antioxidant, its impact on oxidative stress, and its regulation of redox homeostasis. However, the specific molecular biological mechanisms through which HRW improves athletic performance remain to be fully elucidated. Full article

(This article belongs to the Section Nutrition and Metabolism)

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16 pages, 2225 KiB

Open AccessArticle

Resistant Potato Starch Supplementation Reduces Serum Free Fatty Acid Levels and Influences Bile Acid Metabolism

by Jason R. Bush, Izuchukwu Iwuamadi, Jun Han, David J. Schibli, David R. Goodlett and Edward C. Deehan

Metabolites 2024, 14(10), 536; https://doi.org/10.3390/metabo14100536 - 5 Oct 2024

Viewed by 763

Abstract

Background: Resistant starches, such as high-amylose maize starch and resistant potato starch (RPS), have prebiotic effects that are linked to improved metabolism at >15 g/day, but the effects at lower doses have not been reported. Methods: We performed an exploratory post [...] Read more.

Background: Resistant starches, such as high-amylose maize starch and resistant potato starch (RPS), have prebiotic effects that are linked to improved metabolism at >15 g/day, but the effects at lower doses have not been reported. Methods: We performed an exploratory post hoc analysis of free fatty acids (FFAs), bile acids (BAs), and ketone bodies in serum previously collected from a randomized, double-blind, placebo-controlled clinical trial evaluating the effects of one- and four-week consumption of 3.5 g/day RPS versus a placebo using two-way ANOVA adjusted by pFDR. Associations between week 4 changes in FFAs, BAs, and ketone bodies were assessed by Pearson’s correlations. Results: RPS consumption reduced total FFAs relative to the placebo, including multiple unsaturated FFAs and octanedioic acid, with reductions in taurine- and glycine-conjugated secondary BAs also detected (q < 0.05). No changes in ketone bodies were observed (q > 0.05). Changes in 7-ketodeoxycholic acid (r = −0.595) and glycolithocholic acid (r = −0.471) were inversely correlated with treatment-induced reductions in FFAs for RPS but not the placebo, suggesting the effects were from the prebiotic. Shifts in β-hydroxybutyrate were further correlated with FFA changes in both treatments (q < 0.05). Conclusions: These findings demonstrate that low doses of RPS positively influence fatty acid metabolism in humans, reducing circulating levels of FFA and conjugated BAs. Full article

(This article belongs to the Special Issue Functional Foods and Natural Bioactive Compounds: Strategies to Face Metabolic Syndrome and Related Non-communicable Diseases)

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Graphical abstract

Graphical abstract
Full article ">Figure 1
Effects of RPS and placebo on FFA levels. Total FFA levels were not different between placebo and RPS groups across baseline, week 1, and week 4 (A). RPS significantly reduced total FFA levels compared to placebo (B). Individual FFAs were similarly distributed in both placebo and RPS groups across baseline, week 1, and week 4 (C). Pooled unsaturated fats, including FA(8:1), FA(10:1), FA(12:1), FA(14:1), FA(16:1), FA(18:1), FA(18:2), FA(18:3), FA(18:4), FA(20:1), FA(20:2), FA(20:3), FA(20:4), FA(20:5), FA(22:1), FA(22:4), FA(22:5), FA(22:6), and FA(24:1), were reduced by RPS when compared to placebo (D). Saturated fats, including FA(7:0), FA(8:0), FA(9:0), FA(10:0), FA(11:0), FA(12:0), FA(13:0), FA(14:0), FA(15:0), FA(16:0), FA(17:0), FA(18:0), FA(19:0), FA(20:0), FA(21:0), FA(22:0), FA(23:0), FA(24:0), FA(25:0), and FA(26:0), were not significantly reduced in the RPS group compared to the placebo (E). See <a href="#app1-metabolites-14-00536" class="html-app">Table S1</a> for full analysis. (ANOVA; mean ± SEM). Full article ">Figure 2
Effects of RPS and placebo on bile acid levels. Total bile acid levels were not significantly different between placebo and RPS groups across baseline, week 1 and week 4 (A). Changes in total bile acid levels tended to decrease in the RPS group compared to the placebo group, but this effect was not significant (B). Conjugated (C) and unconjugated (D) bile acid levels were similar in both treatment groups across baseline, week 1, and week 4. Total conjugated (E) and glycine-conjugated (F) bile acids tended to be reduced in the RPS group. RPS consumption significantly reduced taurine-conjugated bile acids (G) but had no effect on unconjugated bile acids (H). (ANOVA; mean ± SEM). Full article ">Figure 3
Effects of RPS and placebo on 7-ketodeoxycholic acid levels. Week 4 changes in 7-ketodeoxycholic acid are correlated with changes in FFA levels in the RPS but not placebo group (A). Levels of 7-ketodeoxycholic acid were not different between groups across baseline, week 1, or week 4 (B), nor were changes in 7-ketodeoxycholic acid between groups (C). (ANOVA; mean ± SEM). Full article ">Figure 4
Effects of RPS and placebo on ketone bodies. Week 4 changes in β-hydroxybutyrate were significantly correlated with changes in FFA levels in both placebo and RPS (A) groups. Week 4 changes in acetoacetate were significantly correlated with changes in acetate levels in both placebo and RPS (B) groups. Week 4 changes in β-hydroxybutyrate were significantly correlated with changes in acetate levels in both placebo and RPS (C) groups. Week 4 changes in β-hydroxybutyrate were significantly correlated with changes in acetoacetate levels in both placebo and RPS (D) groups. β-hydroxybutyrate levels were not significantly different between placebo and RPS groups across baseline, week 1, or week 4 (E), nor were changes in β-hydroxybutyrate between treatment groups (F). (ANOVA; mean ± SEM). Full article ">Figure 5
Interactions between FFAs, bile acids, and ketone bodies. Heatmap shows associations between week 4 changes in select FFAs, bile acids, and ketone bodies in the placebo (A) and RPS (B) groups. Color gradient indicates Pearson correlation coefficients; * q values < 0.05. Full article ">Figure 6
Effects of RPS and placebo on glycolithocholic acid levels. Week 4 changes in glycolithocholic acid are correlated with changes in FFA levels in the RPS group but not the placebo group (A). Levels of glycolithocholic acid were not significantly different between treatment group across baseline, week 1, and week 4 (B), but changes in glycolithocholic acid between treatment groups were significantly different (C). (ANOVA; mean ± SEM). Full article ">

13 pages, 600 KiB

Open AccessArticle

Association between Inflammatory and Metabolic Biomarkers and Common Mental Disorders among Adults: 2015 Health Survey of São Paulo, SP, Brazil

by Letícia do Nascimento Maximiano Ferreira, Regina Mara Fisberg, Flavia Mori Sarti and Marcelo Macedo Rogero

Metabolites 2024, 14(10), 535; https://doi.org/10.3390/metabo14100535 - 5 Oct 2024

Viewed by 401

Abstract

Recent studies suggest that plasma inflammatory biomarker concentrations may represent valuable indicators for the diagnosis and prognosis of mental disorders. At the same time, metabolic alterations may contribute to the development and progression of systemic low-grade inflammation. Background/Objectives: This study evaluated the [...] Read more.

Recent studies suggest that plasma inflammatory biomarker concentrations may represent valuable indicators for the diagnosis and prognosis of mental disorders. At the same time, metabolic alterations may contribute to the development and progression of systemic low-grade inflammation. Background/Objectives: This study evaluated the association between plasma inflammatory biomarkers and common mental disorders (CMD), exploring the relationship between metabolic biomarkers, metabolic syndrome (MetS), and inflammatory biomarkers in younger and older adults. Methods: This cross-sectional study used data from the 2015 Health Survey of São Paulo with a Focus on Nutrition Study. The occurrence of CMD was assessed through the Self-Reporting Questionnaire (SRQ-20). Blood samples were used to measure plasma concentrations of inflammatory and cardiometabolic biomarkers. MetS was defined according to the International Diabetes Federation Consensus. The Mann–Whitney test compared inflammatory biomarker concentrations across CMD groups and cardiometabolic conditions, and logistic regression models explored associations between inflammatory biomarker concentration and CMD. Results: The sample included 575 participants, 22.6% (n = 130) of whom had CMD. Concentrations of plasminogen activator inhibitor 1, C-reactive protein (CRP), and the systemic low-grade inflammation score varied significantly among CMD groups. CRP concentrations were positively associated with the presence of CMD, independent of confounding factors. Participants with insulin resistance, dyslipidemia, and MetS exhibited significantly higher CRP concentrations than individuals without these conditions. Conclusions: The findings suggest that increased plasma CRP concentrations may be a potential risk factor for CMD. Higher CRP concentrations were observed in individuals with insulin resistance, dyslipidemia, and MetS. Future interventional studies should explore these hypotheses in diverse populations. Full article

(This article belongs to the Section Endocrinology and Clinical Metabolic Research)

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13 pages, 861 KiB

Open AccessArticle

A Proposal for a Noxious Stimuli-Free, Moderate-Intensity Treadmill Running Protocol to Improve Aerobic Performance in Experimental Research on Rats

by Gilmara Gomes de Assis, Elda Olivia Nobre de Souza, Paulo Francisco de Almeida-Neto, Halil İbrahim Ceylan and Nicola Luigi Bragazzi

Metabolites 2024, 14(10), 534; https://doi.org/10.3390/metabo14100534 - 4 Oct 2024

Viewed by 477

Abstract

Background/Objectives: Animal models can help understand human physiological responses, including the response to exercise and physical activity. However, many of these models incorporate noxious stimuli for various scientific purposes. We propose a noxious stimuli-free treadmill running training program for Rattus norvegicus species to [...] Read more.

Background/Objectives: Animal models can help understand human physiological responses, including the response to exercise and physical activity. However, many of these models incorporate noxious stimuli for various scientific purposes. We propose a noxious stimuli-free treadmill running training program for Rattus norvegicus species to study adaptations to aerobic exercise. Methods: In this study, rats were randomly allocated to training (n = 20) and sedentary (n = 20) groups. The training group underwent a program consisting of 30–50 min of treadmill running at 60% intensity, three times per week for 8 weeks. Maximum speed tasks (Tmax) were conducted to determine, adjust, and evaluate changes in fitness conditions. The rats had one week of familiarization with the treadmill, and a rubber ball was used at the back wall of the lane as a painless stimulus to encourage running. All assessments were conducted by two independent researchers in a double-blind manner, with data analysis conducted by a third-blind investigator. Results: A significant effect of time (η²_p = 0.430, p < 0.001, large effect) could be found, showing differences between Tmax1 and Tmax2, and between Tmax1 and Tmax3 in both groups. The training group significantly outperformed the sedentary group (η²_p = 0.266, p < 0.001, large effect). There was a significant interaction between time and condition (η²_p = 0.152, p < 0.001, large effect). Conclusions: The proposed moderate-intensity treadmill running program could effectively differentiate between trained and sedentary conditions within both the short period of 4 weeks and the extended period of 8 weeks. This protocol can be used as a model for running on a treadmill for Rattus norvegicus species without the use of noxious stimuli. Full article

(This article belongs to the Section Endocrinology and Clinical Metabolic Research)

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16 pages, 1838 KiB

Open AccessArticle

Comparative Impact of Organic Grass-Fed and Conventional Cattle-Feeding Systems on Beef and Human Postprandial Metabolomics—A Randomized Clinical Trial

by Meghan Spears, Gwendolyn Cooper, Brett Sather, Marguerite Bailey, Jane A. Boles, Brian Bothner and Mary P. Miles

Metabolites 2024, 14(10), 533; https://doi.org/10.3390/metabo14100533 - 3 Oct 2024

Viewed by 736

Abstract

Background/Objectives: Cattle-feeding systems may have health implications for consumers of beef products. Organic grass-fed (GRA) and conventional (CON) cattle-feeding systems may result in beef products with differing metabolite profiles and therefore could impact the postprandial metabolomic response of consumers. This study aims to [...] Read more.

Background/Objectives: Cattle-feeding systems may have health implications for consumers of beef products. Organic grass-fed (GRA) and conventional (CON) cattle-feeding systems may result in beef products with differing metabolite profiles and therefore could impact the postprandial metabolomic response of consumers. This study aims to measure whole beef metabolomics and postprandial metabolomic response of consumers between GRA and CON beef to elucidate potential health implications. Methods: This study followed a randomized double-blind crossover design with healthy male and female subjects (n = 10). Plasma samples were taken at fasting (0) and postprandially for four hours after consumption of a steak from each condition. Untargeted metabolomic analysis of whole beef and human plasma samples used LC/MS. Multivariate and pathway enrichment analysis in MetaboAnalyst was used to investigate metabolite and biochemical pathways that distinguished CON and GRA. Results: Cattle-feeding systems impacted both postprandial and whole beef steak metabolomic profiles. Metabolites that contributed to this variation included carnitine species (Proionylcarnitine), fatty acids, amino acids (L-valine), and Calamendiol. These metabolites have been associated with oxidative stress, inflammation, and cardiovascular health. Functional pathway enrichment analysis revealed numerous amino acid degradation pathways, especially branched-chain amino acids, and fatty acid degradation that changed throughout the postprandial time course. Conclusions: These findings suggest that CON and GRA cattle-feeding systems differentially impact whole beef metabolomics, as well as consumer postprandial metabolic responses and the associated health implications. Full article

(This article belongs to the Section Endocrinology and Clinical Metabolic Research)

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Graphical abstract

Graphical abstract
Full article ">Figure 1
CONSORT flow chart. Full article ">Figure 2
Multivariate statistics of CON versus GRA steaks. (A) PCA scores plot of CON (gold) and GRA (violet) beef steaks. PC1 describes 35.6% of total variation. PC2 represents 15.2% of total variation. Ovals represent 95% confidence intervals. (B) PLS-DA scores plot of CON versus GRA beef steaks. PC1 described 21.1% of total variation. PC2 described 25.5% of total variation. Ovals represent 95% confidence intervals. (C) PCHA heat map of the top 25 features, filtered by lowest p-value. Samples are clustered in columns and features are clustered in rows. The intersection represents the feature abundance of the sample, relative to the average. Red indicates high abundance and blue represents low abundance. Full article ">Figure 3
PLS-DA showing postprandial metabolomic profiles in human plasma (n = 10) between CON and GRA at (A) fasting, (B) hour 0.5, (C) hour 1, (D) hour 1.5, (E) hour 2, (F) hour 2.5, (G) hour 3, (H) hour 3.5, and (I) hour 4. All features included in analysis. Ovals represent 95% confidence intervals. All features were included to generate these plots. The greatest separation in postprandial metabolic profiles between GRA and CON occurred at hour 1.5, followed by moderate separation in hours 2–4. Full article ">Figure 4
Time course of enriched pathways from functional pathway enrichment analysis. All features included in analysis. Pathways altered based on the untargeted metabolomics data (0–4 h) are shown. Fat and protein metabolism dominated metabolic pathways that were enriched after the consumption of CON and GRA beef. Horizontal bars coincide with the timepoint(s) when the pathway was enriched. Color shading (orange, blue, green, purple, yellow) relates to the type of metabolism pathway. Full article ">

14 pages, 1007 KiB

Open AccessArticle

Nontargeted Metabolomics to Understand the Impact of Modified Atmospheric Packaging on Metabolite Profiles of Cooked Normal-pH and Atypical Dark-Cutting Beef

by Keayla M. Harr, Noah Jewell, Gretchen G. Mafi, Morgan M. Pfeiffer and Ranjith Ramanathan

Metabolites 2024, 14(10), 532; https://doi.org/10.3390/metabo14100532 - 2 Oct 2024

Viewed by 491

Abstract

Background: Limited knowledge is currently available on the effects of modified atmospheric packaging (MAP) on the metabolite profiles of cooked beef. The objective was to evaluate the impact of packaging on the cooked color and cooked metabolite profile of normal-pH (normal bright-red [...] Read more.

Background: Limited knowledge is currently available on the effects of modified atmospheric packaging (MAP) on the metabolite profiles of cooked beef. The objective was to evaluate the impact of packaging on the cooked color and cooked metabolite profile of normal-pH (normal bright-red color) and atypical-dark-cutting beef (inherently slightly dark-colored) longissimus lumborum muscle. Methods: Normal-pH (pH 5.56) and atypical dark-cutting (pH 5.63) loins (n = 6) were procured from a commercial meat processor. Steaks were randomly assigned to one of three different packaging methods: vacuum packaging, carbon monoxide (CO-MAP), and high oxygen (HiOx-MAP). Following 5 d of retail display, steaks were cooked to 71 °C on a clamshell-style grill, and samples were collected for untargeted metabolites using gas-chromatography mass spectrometry. Results: Raw atypical dark-cutting steaks were less red (p < 0.05) than raw normal-pH steaks. However, there were no differences in internal cooked color between normal-pH and atypical dark-cutting steaks. Steaks packaged in HiOx-MAP steaks had a lower (p < 0.05) cooked redness than vacuum and CO-MAP steaks. A total of 129 metabolite features were identified in the study. Serine and tryptophan were over-abundant in cooked atypical dark-cutting beef compared to raw atypical samples. Citric acid levels were greater in HiOx-MAP packaged beef compared with VP both in normal and atypical dark-cutting beef after cooking, while no differentially abundant metabolites were shared between vacuum and CO-MAP steaks after cooking. Discussion: A slight increase in pH did not influence metabolite profiles in different packaging. However, there were packaging effects within normal and atypical dark-cutting beef. Conclusions: This study suggests that packaging conditions change metabolite profiles, which can influence cooked metabolites. Therefore, the metabolomics approach can be used to better understand cooked color defects such as premature browning. Full article

(This article belongs to the Section Food Metabolomics)

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19 pages, 1977 KiB

Open AccessArticle

Salivary Metabolites in Breast Cancer and Fibroadenomas: Focus on Menopausal Status and BMI

by Elena I. Dyachenko and Lyudmila V. Bel’skaya

Metabolites 2024, 14(10), 531; https://doi.org/10.3390/metabo14100531 - 30 Sep 2024

Viewed by 432

Abstract

This study of the features of the biochemical composition of biological fluids in patients with breast cancer, including saliva, allows us to identify some indicators as metabolic predictors of the presence of the disease. Objectives: to study the influence of the menopause factor [...] Read more.

This study of the features of the biochemical composition of biological fluids in patients with breast cancer, including saliva, allows us to identify some indicators as metabolic predictors of the presence of the disease. Objectives: to study the influence of the menopause factor and body mass index (BMI) on the biochemical composition of saliva and to evaluate the applicability of metabolic markers of saliva for the diagnosis of breast cancer. Methods: The case–control study involved 1438 people (breast cancer, n = 543; fibroadenomas, n = 597; control, n = 298). A comprehensive study of the biochemical composition of saliva was carried out using 36 parameters. Results: When comparing the salivary biochemical composition in breast cancer, fibroadenomas, and controls, it is necessary to take into account the menopausal status, as well as BMI (less than 25 or more) for the group of patients with preserved menstrual function. A complex of biochemical parameters has been identified that change in saliva during breast cancer, regardless of menopause and BMI (total protein, urea, uric acid, NO, α-amino acids, GGT), as well as specific parameters that must be taken into account when analyzing individual subgroups (imidazole compounds, LDH, catalase, α-amylase). During the study of a separate group of patients with leaf-shaped (phyllodes) tumors, we found similarities with breast cancer in the changes in some biochemical parameters that can be attributed to metabolites of malignant growth (protein, α-amino acids, calcium, NO, pyruvate, peroxidase, α-amylase). Conclusions: We demonstrated changes in a wide range of salivary biochemical parameters depending on the presence of fibroadenomas and breast cancer. From the point of view of clinical practice, this may be useful information for monitoring the condition of patients with fibroadenomas, which are difficult to unambiguously classify based on instrumental diagnostics alone. Full article

(This article belongs to the Special Issue Investigation of the Metabolic Mechanisms Underlying Breast Cancer: Navigating from Diagnosis to Survivorship)

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5 pages, 182 KiB

Open AccessEditorial

Environmental Toxicology and Metabolism

by Yu Sun

Metabolites 2024, 14(10), 530; https://doi.org/10.3390/metabo14100530 - 30 Sep 2024

Viewed by 488

Abstract

The modern world is witnessing an unprecedented rise in environmental exposures to hazardous substances such as pesticides, heavy metals, and synthetic chemicals [...] Full article

(This article belongs to the Special Issue Environmental Toxicology and Metabolism)

11 pages, 517 KiB

Open AccessArticle

Peripheral Brain-Derived Neurotrophic Factor (BDNF) and Its Regulatory miRNAs as Biological Correlates of Impulsivity in Young Adults

by Przemyslaw Zakowicz, Beata Narozna, Tomasz Kozlowski, Weronika Bargiel, Maksymilian Grabarczyk, Maria Terczynska, Julia Pilecka, Karolina Wasicka-Przewozna, Joanna Pawlak and Maria Skibinska

Metabolites 2024, 14(10), 529; https://doi.org/10.3390/metabo14100529 - 30 Sep 2024

Viewed by 528

Abstract

Background: Impulsivity assessment may serve as a valuable clinical tool in the stratification of suicide risk. Acting without forethought is a crucial feature in the psychopathology of many psychiatric disturbances and corresponds with suicidal ideations, behaviors, and attempts. Methods: We present [...] Read more.

Background: Impulsivity assessment may serve as a valuable clinical tool in the stratification of suicide risk. Acting without forethought is a crucial feature in the psychopathology of many psychiatric disturbances and corresponds with suicidal ideations, behaviors, and attempts. Methods: We present data on biological and psychological correlates of impulsivity among young adults (n = 47). Psychological analysis included both the self-description questionnaire—Barratt Impulsiveness Scale (BIS-11)—and neuropsychological behavioral tests, including the Iowa Gambling Task (IGT), the Simple Response Time task (SRT), and the Continuous Performance Test (CPT). mRNA and micro-RNA were isolated from peripheral blood mononuclear cells (PBMC). Expression levels of Brain-Derived Neurotrophic Factor (BDNF) mRNA and its regulatory micro RNAs, mir-1-3p, mir-15a-5p, mir-26a-5p, mir-26b-5p, and mir-195-5p, were analyzed using the quantitative reverse transcription polymerase chain reaction (RT-qPCR) method. proBDNF and BDNF plasma protein levels were quantified using enzyme-linked immunosorbent assay (ELISA). Results: Significant correlations between BDNF mRNA and mir-15a-5p as well as proBDNF levels and mir-1-3p were detected. proBDNF protein levels correlated with motor and perseverance, while mir-26b correlated with cognitive complexity subdimensions of the BIS-11 scale. Correlations between BDNF, miRNAs, and the results of neuropsychological tests were also detected. Conclusions: The BDNF pathway shows a clinical potential in searching for biomarkers of impulse-control impairment. BDNF-regulatory micro-RNAs are detectable and related to clinical parameters in the studied population, which needs further research. Full article

(This article belongs to the Special Issue Cellular Metabolism in Neurological Disorders)

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5 pages, 175 KiB

Open AccessEditorial

Do Sex and Gender-Related Differences Account to Different Risk of Developing Heart Failure in Middle-Aged People with Metabolic Syndrome?

by Stefano Bonapace and Alessandro Mantovani

Metabolites 2024, 14(10), 528; https://doi.org/10.3390/metabo14100528 - 30 Sep 2024

Viewed by 520

Abstract

Metabolic syndrome (MetS) is not a disease but a constellation of metabolic abnormalities that together increase the risk of developing cardiovascular disease (CVD) [...] Full article

(This article belongs to the Section Endocrinology and Clinical Metabolic Research)

15 pages, 3638 KiB

Open AccessArticle

Based on Sportomics: Comparison of Physiological Status of Collegiate Sprinters in Different Pre-Competition Preparation Periods

by Pengyu Fu, Xiaomin Duan, Yuting Zhang, Xiangya Dou and Lijing Gong

Metabolites 2024, 14(10), 527; https://doi.org/10.3390/metabo14100527 - 29 Sep 2024

Viewed by 453

Abstract

This study aimed to assess the impact of pre-competition training by comparing the differences of collegiate sprinters in physiological state between strengthening and tapering training period by sportomics and combining their sport performance. Fifteen collegiate sprinters were investigated or tested on their body [...] Read more.

This study aimed to assess the impact of pre-competition training by comparing the differences of collegiate sprinters in physiological state between strengthening and tapering training period by sportomics and combining their sport performance. Fifteen collegiate sprinters were investigated or tested on their body composition, dietary habits, energy expenditure, sleep efficiency, heart rate and respiratory rate during training, blood (blood cells, biochemical and immune markers) and urine (urinalysis), gut microbiome distribution, microbiome and blood metabolites, and their functions during the strengthening (Group A) and tapering training period (Group B) prior to competing in the national competitions. We found that 26.67% of sprinters achieved personal bests (PB) after the competition. The limb skeletal muscle mass and lymphocyte ratio of male sprinters in Group B were lower than those in Group A, and the serum creatine kinase (CK) level was higher than Group A (p < 0.05). The levels of serum CK, interleukin-6 (IL-6), interleukin-1β (IL-1β), and urine-specific gravity (SG) of the two groups were higher than the upper limit of the reference value. The detection rates of urine white blood cell (WBC) and protein in Group B were higher than those in Group A. The gut microbiome health index (GMHI) of Group A was higher than that of Group B, and the microbial dysbiosis index was lower than that of Group B. The ratio of Firmicutes/Bacteroidota (F/B) in Group A was higher than that in Group B. There were 65 differential metabolites in the A/B group, and the enriched pathway was mainly the NF-kappa B signaling pathway (up); B/T cell receptor signaling pathway (up); Th1 and Th2 cell differentiation (up); phenylalanine metabolism (up); and growth hormone synthesis, secretion, and action (up). There were significant differences in blood metabolites between the A and B groups, with a total of 89 differential metabolites, and the enriched pathway was mainly the NF-kappa B signaling pathway (up), T cell receptor signaling pathway (up), Th1 and Th2 cell differentiation (up), and glycerophospholipid metabolism (down). In conclusion, the imbalance of the gut microbiome and inflammation and immune-related metabolites of collegiate sprinters during the pre-competition tapering training period may be the cause of their limited sports performance. Full article

(This article belongs to the Special Issue Interactions between Exercise Physiology and Metabolism)

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Conditions for collecting biological samples from sprinters. Full article ">Figure 2
The energy metabolism and sleep efficiency of the sprinters (n = 15). (a1) The three major nutrient energy intake ratio; (a2) the average daily energy intake; (b) the average daily energy expenditure; (c) the sleep efficiency. Compared with Group A-Male, *** p < 0.001. Full article ">Figure 3
Bacterial community characterization index and composition analysis of sprinters (n = 15). (a1) The gut microbiome health index; (a2) the microbial dysbiosis index. Compared with Group A, *** p < 0.001. The community distribution of Group A (b1) and Group B (b2). “p” represents phylu. Full article ">Figure 4
Differential metabolites of the gut microbiome of sprinters and their enriched pathways (n = 15). (a) The principal component analysis (PCA); (b) the volcano plot of differential metabolites; (c) the variable importance in the projection (VIP) analysis chart; (d) the differential abundance score plot of the KEGG pathway. Compared with Group A, * p < 0.05, ** p < 0.01, *** p < 0.001. Full article ">Figure 5
Differential metabolites of the blood of sprinters and their enriched pathways (n = 15). (a) The PCA. (b) The volcano plot of differential metabolites. (c) The VIP analysis chart. (d) The differential abundance score plot of the KEGG pathway. Compared with Group A, * p < 0.05, ** p < 0.01, *** p < 0.001. Full article ">Figure 5 Cont.
Differential metabolites of the blood of sprinters and their enriched pathways (n = 15). (a) The PCA. (b) The volcano plot of differential metabolites. (c) The VIP analysis chart. (d) The differential abundance score plot of the KEGG pathway. Compared with Group A, * p < 0.05, ** p < 0.01, *** p < 0.001. Full article ">

11 pages, 1770 KiB

Open AccessArticle

Comparative Metabolic Profiling in Drosophila suzukii by Combined Treatment of Fumigant Phosphine and Low Temperature

by Junbeom Lee, Hyun-Kyung Kim, Jong-Chan Jeon, Seung-Ju Seok, Gil-Hah Kim, Hyun-Na Koo and Dae-Weon Lee

Metabolites 2024, 14(10), 526; https://doi.org/10.3390/metabo14100526 - 28 Sep 2024

Viewed by 534

Abstract

Background/Objectives: The mechanisms of action of phosphine are diverse and include neurotoxicity, metabolic inhibition, and oxidative stress; however, its efficacy at low temperatures is unclear. Methods: Comparative metabolomics is suitable for investigating the response of the spotted-wing fly Drosophila suzukii to exposure [...] Read more.

Background/Objectives: The mechanisms of action of phosphine are diverse and include neurotoxicity, metabolic inhibition, and oxidative stress; however, its efficacy at low temperatures is unclear. Methods: Comparative metabolomics is suitable for investigating the response of the spotted-wing fly Drosophila suzukii to exposure toward a combination of cold stimuli and fumigant PH₃. Results: Under this combined exposure, 52 metabolites exhibiting significant differences in stress were identified and their physiological roles were analyzed in the Drosophila metabolic pathway. Most metabolites were involved in amino acids, TCA cycle, and nucleic acids. In addition, the alteration levels of cell membrane lipids, such as glycerophospholipids, sphingolipids, and glycerolipids, clearly showed changes in the combined treatment compared to PH₃ and low temperatures alone. Aconitic acid, a component of the TCA cycle, was completely inhibited by the combined treatment. Conclusions: These results suggest that treatment-specific indicators could be useful biomarkers to indicate the synergistic effects of PH₃ and low temperature on energy metabolism. Full article

(This article belongs to the Section Animal Metabolism)

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Metabolites, Volume 14, Issue 10 (October 2024) – 41 articles

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