Search Results (1,380)

Background: Physical inactivity induces insulin resistance (IR) and metabolic imbalances before any significant changes in adiposity. Recent studies suggest that the beneficial effects of exercise can be potentiated if performed while fasting. This work aimed to compare the subacute effects of fed- and fasted-state single-bout exercise on biochemical parameters and cellular signaling in the metabolism. Methods: The animals were allocated into fed rest (FER), fasting rest (FAR), fed exercise (FEE), and fasting exercise (FAE) groups. The exercise protocol was a 30 min treadmill session at 60% of $\dot{\mathrm{V}}$O_2max. The fasting groups fasted for 8 h before exercise and were killed after 12 h post-exercise. Results: Soleus glycogen concentration increased only in the fasting groups, whereas the triglyceride (TGL) content increased in brown adipose tissue (BAT) and liver in the FAE. The FAE showed decreased plasma total cholesterol concentration compared withthe FAR group. Immunocontent of HSP70, SIRT1, UCP-1, and PGC1-α did not change in any tissue investigated. Conclusions: Our results indicate that physical exercise while fasting can have beneficial metabolic effects on sedentary animals. Remarkably, in the FAE group, there was a reduction in total plasma cholesterol and an increase in the capacity of BAT to metabolize and store nutrients in the form of TGLs. Full article

The regulation of energy in the brain has garnered substantial attention in recent years due to its significant implications in various disorders and aging. The brain’s energy metabolism is a dynamic and tightly regulated network that balances energy demand and supply by engaging complementary molecular pathways. The crosstalk among these pathways enables the system to switch its preferred fuel source based on substrate availability, activity levels, and cell state-related factors such as redox balance. Brain energy production relies on multi-cellular cooperation and is continuously supplied by fuel from the blood due to limited internal energy stores. Astrocytes, which interface with neurons and blood vessels, play a crucial role in coordinating the brain’s metabolic activity, and their dysfunction can have detrimental effects on brain health. This review characterizes the major energy substrates (glucose, lactate, glycogen, ketones and lipids) in astrocyte metabolism and their role in brain health, focusing on recent developments in the field. Full article

Glaucoma, an optic neuropathy with the loss of retinal ganglion cells (RGCs), is a leading cause of irreversible vision loss. Oxidative stress and mitochondrial dysfunction have a significant role in triggering glia-driven neuroinflammation and subsequent glaucomatous RGC degeneration in the context of glaucoma. It has previously been shown that apolipoprotein A-I binding protein (APOA1BP or AIBP) has an anti-inflammatory function. Moreover, Apoa1bp^−/− mice are characterized by retinal neuroinflammation and RGC loss. In this study, we found that AIBP deficiency exacerbated the oxidative stress-induced disruption of mitochondrial dynamics and function in the retina, leading to a further decline in visual function. Mechanistically, AIBP deficiency-induced oxidative stress triggered a reduction in glycogen synthase kinase 3β and dynamin-related protein 1 phosphorylation, optic atrophy type 1 and mitofusin 1 and 2 expression, and oxidative phosphorylation, as well as the activation of mitogen-activated protein kinase (MAPK) in Müller glia dysfunction, leading to cell death and inflammatory responses. In vivo, the administration of recombinant AIBP (rAIBP) effectively protected the structural and functional integrity of retinal mitochondria under oxidative stress conditions and prevented vision loss. In vitro, incubation with rAIBP safeguarded the structural integrity and bioenergetic performance of mitochondria and concurrently suppressed MAPK activation, apoptotic cell death, and inflammatory response in Müller glia. These findings support the possibility that AIBP promotes RGC survival and restores visual function in glaucomatous mice by ameliorating glia-driven mitochondrial dysfunction and neuroinflammation. Full article

Heavy metal pollution is a serious global environmental issue. It threatens human and ecological health. Heavy metals can accumulate in the soil over extended periods and inevitably transfer through the food chain to herbivorous insects and their natural enemies, leading to various adverse effects. This study aimed to investigate the stress responses and biochemical metabolic changes of aphids and one of aphids’ predators, ladybugs, under cadmium (Cd) and lead (Pb) stress by constructing a food chain of Vicia faba L., Megoura crassicauda, and Harmonia axyridis. The results showed that aphids and ladybugs had a notable accumulation of Cd²⁺ and Pb²⁺. Insects can adapt to heavy metal stress by regulating their energy metabolism pathways. Glycogen content in the first filial generation (F1) aphids decreased significantly, glucose content in the second filial generation (F2) to the fourth filial generation (F4) adult aphids significantly increased, and trehalose content in the F1 adult aphids increased significantly. Moreover, the relative expression levels of trehalase (TRE) and trehalose-6-phosphate synthase (TPS) in the F1 adult aphids were significantly higher than those in the control group, and the expression levels of TPS genes in the second filial generation to the fifth filial generation (F2 to F5) aphids decreased, suggesting that insects can resist heavy metal stress by regulating trehalose metabolism. The fertility of female aphids in all treatment groups was reduced compared to the control group. Additionally, the relative expression level of vitellogenin (Vg) was down-regulated in all aphid generations except the F1 aphids. There was interaction between heavy metal concentration and aphid generation, and it significantly affected the number of aphids’ offspring and the expression of the aphid Vg gene. The developmental duration of the ladybugs from the second to fourth instars was prolonged, and the weight decreased significantly from the prepupa to the adult stages. These results contribute to understanding the effects of Cd²⁺–Pb²⁺ accumulation on phytophagous insects and higher trophic levels’ natural enemies, laying the foundation for protecting natural enemies and maintaining ecosystem stability. Full article

Ginseng has anti-hyperglycemic effects. Gintonin, a glycolipoprotein derived from ginseng, also stimulates insulin release from pancreatic beta cells. However, the role of gintonin in glucose metabolism within skeletal muscle is unknown. Here, we showed the effect of gintonin on glucose uptake, glycogen content, glucose transporter (GLUT) 4 expression, and adenosine triphosphate (ATP) content in C2C12 myotubes. Gintonin (3–30 μg/mL) dose-dependently stimulated glucose uptake in myotubes. The expression of GLUT4 on the cell membrane was increased by gintonin treatment. Treatment with 1–3 μg/mL of gintonin increased glycogen content in myotubes, but the content was decreased at 30 μg/mL of gintonin. The ATP content in myotubes increased following treatment with 10–100 μg/mL gintonin. Gintonin transiently elevated intracellular calcium concentrations and increased the phosphorylation of extracellular signal-regulated kinase (ERK). Gintonin-induced transient calcium increases were inhibited by treatment with the lysophosphatidic acid receptor inhibitor Ki16425, the phospholipase C inhibitor U73122, and the inositol 1,4,5-trisphosphate receptor antagonist 2-aminoethoxydiphenyl borate. Gintonin-stimulated glucose uptake was decreased by treatment with U73122, the intracellular calcium chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetra(acetoxymethyl) ester, and the ERK inhibitor PD98059. These results show that gintonin plays a role in glucose metabolism by increasing glucose uptake through transient calcium increases and ERK signaling pathways. Thus, gintonin may be beneficial for glucose metabolism control. Full article

This study aimed to evaluate the effects of dietary digestible protein levels on the growth dynamics and oxidative stress status of white muscle fibers in Amazonian Pintado (Pseudoplatystoma reticulatum × Leiarius marmoratus). Four hundred and fifty-five juveniles of Amazonian Pintado were fed diets containing varying digestible protein levels (225, 250, 275, 300, 325, 350, or 375 g kg⁻¹) for 75 days. At the end of the experiment, the fish were fasted for 24 h, anesthetized, and euthanized to obtain muscle samples. The linear and quadratic effects of dietary digestible protein levels on white muscle fiber diameter, metabolite concentrations, and oxidative stress were assessed. The results revealed that increasing dietary digestible protein levels linearly raised the concentrations of free amino acids and total proteins in muscle tissue but also led to elevated levels of TBARS, indicating increased oxidative stress. Notably, the average area of muscle fibers with a cell area greater than 1133 µm² decreased, reflecting restricted muscle hypertrophy, whereas glycogen and glucose levels also declined. These findings suggest that although high dietary digestible protein enhances protein and free amino acid concentrations in muscle tissue, it may compromise muscle hypertrophy and increase oxidative damage in Amazonian Pintado, underscoring the complexity of optimizing diet formulation. Full article

Adipose tissue plays an important role in pig production efficiency. Studies have shown that postnatal development has a vital impact on adipose tissue; however, the mechanisms behind pig adipose tissue early-life programming remain unknown. In this study, we analyzed the transcriptomes of the subcutaneous adipose tissue (SAT) of 1-day and 21-day old Laiwu piglets. The results showed that the SAT of Laiwu piglets significantly increased from 1-day to 21-day, and transcriptome analysis showed that there were 2352 and 2596 differentially expressed genes (DEGs) between 1-day and 21-day SAT in male and female piglets, respectively. Expression of genes in glycolysis, gluconeogenesis, and glycogen metabolism such as pyruvate kinase M1/2 (PKM), phosphoenolpyruvate carboxy kinase 1 (PCK1) and amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase (AGL) were significantly different between 1-day and 21-day SAT. Genes in lipid uptake, synthesis and lipolysis such as lipase E (LIPE), acetyl-CoA carboxylase alpha (ACACA), Stearoyl-CoA desaturase (SCD), and 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) were also differentially expressed. Functional analysis showed enrichment of DEGs in transcriptional regulation, protein metabolism and cellular signal transduction. The protein–protein interaction (PPI) networks of these DEGs were analyzed and potential hub genes in these pathways were identified, such as transcriptional factors forkhead box O4 (FOXO4), CCAAT enhancer binding protein beta (CEBPB) and CCAAT enhancer binding protein delta (CEBPD), signal kinases BUB1 mitotic checkpoint serine/threonine kinase (BUB1) and cyclin-dependent kinase 1 (CDK1), and proteostasis-related factors ubiquitin conjugating enzyme E2 C (UBE2C) and cathepsin D (CTSD). Moreover, we further analyzed the transcriptomes of SAT between genders and the results showed that there were 54 and 72 DEGs in 1-day and 21-day old SAT, respectively. Genes such as KDM5D and KDM6C showed gender-specific expression in 1-day and 21-day SAT. These results showed the significant changes in SAT between 1-day and 21-day in male and female Laiwu pigs, which would provide information to comprehensively understand the programming of adipose tissue early development and to regulate adipose tissue function. Full article

The insulin receptor (IR) plays a crucial role in the growth and metabolism of animals. However, there are still many questions regarding the IR in crustaceans, particularly their role in shrimp growth and glucose metabolism. In this study, we identified a novel insulin-like receptor gene in Litopenaeus vannamei and cloned its full length of 6439 bp. This gene exhibited a highly conserved sequence and structural characteristics. Phylogenetic analysis confirmed it as an unreported RTK2-type IR, namely, LvRTK2. Expression pattern analysis showed that LvRTK2 is primarily expressed in female reproductive and digestive organs. Through a series of in vivo and in vitro experiments, including glucose treatment, exogenous insulin treatment, and starvation treatment, LvRTK2 was confirmed to be involved in the endogenous glucose metabolic pathway of shrimp under different glucose variations. Moreover, long-term and short-term interference experiments with LvRTK2 revealed that the interference significantly reduced the shrimp growth rate and serum glucose clearance rate. Further studies indicated that LvRTK2 may regulate shrimp growth by modulating the downstream PI3K/AKT signaling pathway and a series of glucose metabolism events, such as glycolysis, gluconeogenesis, glycogen synthesis, and glycogenolysis. This report on the characteristics and functions of LvRTK2 confirms the important role of RTK2-type IRs in regulating shrimp growth and glucose metabolism. Full article

The rising occurrence of erectile dysfunction related to diabetes mellitus (DMED) has led to the creation of new medications. Proanthocyanidins (PROs) is a potential agent for DMED. In this study, the DMED rat model was established using streptozotocin (STZ) and erectile function was assessed using apomorphine (APO) in rats. Following this, the rats were subjected to oral treatment with PRO. Then, we evaluated the influence of PROs on DMED rats. The findings suggest that PROs significantly enhance erectile function in DMED rats. PROs modulated glucose and lipid metabolism in DMED rats by decreasing blood glucose and lipid levels while increasing liver glycogen and serum insulin levels. Furthermore, PROs enhanced vascular endothelial function in DMED rats by augmenting nitric oxide (NO) levels and reducing the levels of endothelin-1 (ET-1) and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). Additionally, PROs have been shown to elevate testosterone (T) levels, mitigate pathological testicular damage, and enhance sperm concentration and survival rates. Finally, the core targets were screened using network pharmacology, followed by validation through molecular docking, enzyme-linked immunoassay (ELISA), and real-time PCR methodologies. Our findings imply that PROs may treat DMED by elevating AKT1 levels while concurrently diminishing CASP3 levels, thereby effectively regulating the PI3K-Akt signaling pathway. Overall, these results support using PROs as a potential candidate for the treatment of DMED. Full article

The molecular mechanisms by which cardiovascular risk factors promote the development of atherosclerosis are poorly understood. We have recently shown that genetic ablation of myeloid glycogen synthase kinase (GSK)-3α attenuates atherosclerotic lesion development in low-density lipoprotein receptor-deficient (Ldlr^−/−) mice. However, the precise contributions of GSK3α/β in atherogenesis are not known. The aim of this study is to investigate the effect of GSK3α and/or β deficiency on lesional inflammation and plaque vascularization. Five-week-old female Ldlr^−/− mice were fed a high-fat diet for 10 weeks to establish atherosclerotic lesions. Mice were harvested at 15 weeks of age and atherosclerotic lesions were characterized. The results indicate that, in addition to significantly reducing plaque volume, GSK3α-deficiency decreases inflammation, reduces vasa vasorum density at the aortic sinus, and reduces plasma c-reactive protein (CRP) levels. GSK3β-deficiency is associated with decreased plasma CRP levels but does not affect lesional inflammation or vascularization. These results suggest GSK3α may be an applicable target for the development of novel anti-atherogenic therapies. Full article

Schistosomiasis affects over 250 million people worldwide, with the highest prevalence at the age of 10–14 years. The influence of the host’s age on the severity of liver damage is unclear. We infected male 8, 14, and 20-week-old mice with S. mansoni. Hepatic damage, inflammation, fibrosis, and metabolism were analyzed by RT-qPCR, Western blotting, ELISA, immunohistochemistry, and mechanistic transwell chamber experiments using S. mansoni eggs and human hepatic stellate cells (HSCs) or primary mouse hepatocytes. Major results were validated in human biopsies. We found that hepatosplenomegaly, granuloma size, egg load, inflammation, fibrosis, and glycogen stores all improved with the increasing age of the host. However, serum alanine transaminase (ALT) levels were lowest in young mice infected with S. mansoni. Hepatic carbohydrate exploitation was characterized by a shift towards Warburg-like glycolysis in S. mansoni-infected animals. Notably, S. mansoni eggs stimulated hepatic stellate cells to an alternatively activated phenotype (GFAP⁺/desmin⁺/αSMA⁻) that secretes IL-6 and MCP-1. The reduction of fibrosis in older age likely depends on the fine-tuning of regulatory and inflammatory cytokines, alternative HSC activation, and the age-dependent preservation of hepatic energy stores. The current results emphasize the significance of investigations on the clinical relevance of host age-dependent liver damage in patients with schistosomiasis. Full article

Amyloid β protein (Aβ) deposition has been implicated as the molecular driver of Alzheimer’s disease (AD) progression. The modulation of the formation of abnormal aggregates and their post-translational modification is strongly suggested as the most effective approach to anti-AD. Beta-site APP-cleaving enzyme 1 (BACE1) acts upstream in amyloidogenic processing to generate Aβ, which rapidly aggregates alone or in combination with acetylcholinesterase (AChE) to form fibrils. Accumulated Aβ promotes BACE1 activation via glycogen synthase kinase-3β (GSK-3β) and is post-translationally modified by glutaminyl cyclase (QC), resulting in increased neurotoxicity. A novel multi-target inhibitor as a potential AD agent was identified using an in silico approach and experimental validation. Magnolia officinalis, which showed the best anti-AD activity in our preliminary study, was subjected to analysis, and 82 compounds were studied. Among 23 compounds with drug-likeness, blood–brain barrier penetration, and safety, honokiol emerged as a lead structure for the inhibition of BACE1, AChE, QC, and GSK-3β in docking and molecular dynamics (MD) simulations. Furthermore, honokiol was found to be an excellent multi-target inhibitor of these enzymes with an IC₅₀ of 6–90 μM, even when compared to other natural single-target inhibitors. Taken together, the present study is the first to demonstrate that honokiol acts as a multiple enzyme inhibitor with an excellent pharmacokinetic and safety profile which may provide inhibitory effects in broad-range areas including the overproduction, aggregation, and post-translational modification of Aβ. It also provides insight into novel structural features for the design and discovery of multi-target inhibitors for anti-AD. Full article

The study of sperm characteristics has proven useful for elucidating interrelationships in several groups of Platyhelminthes, such as digeneans. Thus, in the present work, the ultrastructural organization of the mature spermatozoon of the digenean Artyfechinostomum malayanum (Echinostomatidae), a parasite of Rattus norvegicus (Rodentia: Muridae) from Dong Thap Province, Vietnam, was investigated for the first time using transmission electron microscopy. The male gamete of A. malayanum exhibits two axonemes of different lengths, showing the 9 + ‘1’ pattern of the Trepaxonemata, a nucleus, two mitochondria, two lateral expansions, two bundles of parallel cortical microtubules, external ornamentation, spine-like bodies, and granules of glycogen. Thus, the mature spermatozoon follows a Type V sperm model proposed for digeneans. We also highlight some noteworthy characteristics in Echinostomatidae with possible phylogenetic implications, such as two lateral expansions in the anterior region of the spermatozoon and two mitochondria. Full article

The goal of this study was to assess health of male Common Carp (carp, Cyprinus carpio) at four sites with a wide range in environmental organic contaminant (EOC) concentrations and water temperatures in Lake Mead National Recreation Area NV/AZ, US, and the potential influence of regional drought. Histological and reproductive biomarkers were measured in 17–30 carp at four sites and 130 EOCs in water per site were analyzed using passive samplers in 2010. Wide ranges among sites were noted in total EOC concentrations (>10Xs) and water temperature/degree days (10Xs). In 2007/08, total polychlorinated biphenyls (tPCBs) in fish whole bodies from Willow Beach (WB) in the free-flowing Colorado River below Hoover Dam were clearly higher than at the other sites. This was most likely due to longer exposures in colder water (12–14 °C) and fish there having the longest lifespan (up to 54 years) for carp reported in the Colorado River Basin. Calculated estrogenicity in water exceeded long-term, environmentally safe criteria of 0.1–0.4 ng/L by one to three orders of magnitude at all sites except the reference site. Low ecological screening values for four contaminants of emerging concern (CEC) in water were exceeded for one CEC in the reference site, two in WB and Las Vegas Bay and three in the most contaminated site LVW. Fish health biomarkers in WB carp had 25% lower liver glycogen, 10Xs higher testicular pigmented cell aggregates and higher sperm abnormalities than the reference site. Sperm from LVW fish also had significantly higher fragmentation of DNA, lower motility and testis had lower percent of spermatozoa, all of which can impair reproduction. Projections from a 3D water quality model performed for WB showed that EOC concentrations due to prolonged regional drought and reduced water levels could increase as high as 135%. Water temperatures by late 21st century are predicted to rise between 0.7 and 2.1 °C that could increase eutrophication, algal blooms, spread disease and decrease dissolved oxygen over 5%. Full article

The adaptability of marine organisms to changes in salinity has been a significant research area under global climate change. However, the underlying mechanisms of this adaptability remain a debated subject. We hypothesize that neglecting salinity fluctuation properties is a key contributing factor to the controversy. The ciliate Euplotes vannus was used as the model organism, with two salinity fluctuation period sets: acute (24 h) and chronic (336 h). We examined its population growth dynamics and energy metabolism parameters following exposure to salinity levels from 15‰ to 50‰. The carrying capacity (K) decreased with increasing salinity under both acute and chronic stresses. The intrinsic growth rate (r) decreased with increasing salinity under acute stress. Under chronic stress, the r initially increased with stress intensity before decreasing when salinity exceeded 40‰. Overall, glycogen and lipid content decreased with stress increasing and were significantly higher in the acute stress set compared to the chronic one. Both hypotonic and hypertonic stresses enhanced the activities of metabolic enzymes. A trade-off between survival and reproduction was observed, prioritizing survival under acute stress. Under chronic stress, the weight on reproduction increased in significance. In conclusion, the tested ciliates adopted an r-strategy in response to salinity stress. The trade-off between reproduction and survival is a significant biological response mechanism varying with salinity fluctuation properties. Full article