Search Results (134)

Polyunsaturated fatty acids (PUFAs), especially arachidonic acid (ARA) and docosahexaenoic acid (DHA), are extremely important fatty acids for brain development in the fetus and early childhood. Premature infants face challenges obtaining these two fatty acids from their mothers. It has been reported that supplementation with triacylglycerols (TAGs) with an ARA:DHA (w/w) ratio of 2:1 may be optimal for preterm infants, as presented in commercial formulas such as Formulaid™. This study explored methods to produce TAGs with a 2:1 ratio (ARA:DHA), particularly at the more bioavailable sn-2 position of the glycerol backbone. Blending and enzymatic acidolysis of microalgae oil (rich in DHA) and ARA-rich oil yielded products with the desired ARA:DHA ratio, enhancing sn-2 composition compared to Formulaid™ (1.6 for blending and 2.3 for acidolysis versus 0.9 in Formulaid™). Optimal acidolysis conditions were 45 °C, a 1:3 substrate molar ratio, 10% Candida antarctica lipase, and 4 h. The process was reproducible, and scalable, and the lipase could be reused. In vitro digestion showed that 75.5% of the final product mixture was bio-accessible, comprising 19.1% monoacylglycerols, ~50% free fatty acids, 14.6% TAGs, and 10.1% diacylglycerols, indicating better bio-accessibility than precursor oils. Full article

Polymorphic control is vital for the quality control of pharmaceutical crystals. Here, we investigated the relationship between the hydrate and anhydrate polymorphs of a monoacylglycerol acyltransferase 2 inhibitor (S-309309). Solvent evaporation and slurry conversion revealed two polymorphs, the hydrate and the solvate. The solvate was transformed into the hydrate by heating. X-ray powder diffraction demonstrated that the hydrate was transformed into an anhydrate via an intermediate state when heated. These crystal forms were confirmed under controlled humidity conditions; the presence of the anhydrate, the intermediate hydrate, or the hydrate depended on the relative humidity at 25 °C. The stoichiometry of S-309309 in water in the hydrate form was 4:1. The hydrates and anhydrates exhibited similar crystal structures and stability. The water of hydration in the intermediate hydrate was 0.1–0.15 mol according to the dynamic vapor sorption profile. The stability and dissolution profile of the anhydrate and hydrate showed no significant change due to similar crystal lattices and quick rehydration of the anhydrate. A mechanism for the reversible crystal transformation between the anhydrate and pseudo-polymorphs of the hydrate was discovered. We concluded that S-309309 causes a pseudo-polymorphic transformation; however, this is not a critical issue for pharmaceutical use. Full article

The endocannabinoid system, known for its regulatory role in various physiological processes, relies on the activities of several hydrolytic enzymes, such as fatty acid amide hydrolase (FAAH), N-acylethanolamine-hydrolyzing acid amidase (NAAA), monoacylglycerol lipase (MAGL), and α/β-hydrolase domains 6 (ABHD6) and 12 (ABHD12), to maintain homeostasis. Accurate measurement of these enzymes’ activities is crucial for understanding their function and for the development of potential therapeutic agents. Fluorometric assays, which offer high sensitivity, specificity, and real-time monitoring capabilities, have become essential tools in enzymatic studies. This review provides a comprehensive overview of the principles behind these assays, the various substrates and fluorophores used, and advances in assay techniques used not only for the determination of the kinetic mechanisms of enzyme reactions but also for setting up kinetic assays for the high-throughput screening of each critical enzyme involved in endocannabinoid degradation. Through this comprehensive review, we aim to highlight the strengths and limitations of current fluorometric assays and suggest future directions for improving the measurement of enzyme activity in the endocannabinoid system. Full article

Microalgae are currently considered an attractive source of highly valuable metabolites potentially exploitable as anticancer agents, nutraceuticals and cosmeceuticals and for bioenergy purposes. Their ease of culturing and their high growth rates further promote their use as raw material for the production of specialty products. In the present paper, we focused our attention on specific glycerol-based lipid compounds, monoacylglycerols (MAGs), which displayed in our previous studies a selective cytotoxic activity against the haematological U-937 and the colon HCT-116 cancer cell lines. Here, we performed a quali/quantitative analysis of MAGs and total fatty acids (FAs) along with a profiling of the main lipid classes in a panel of 12 microalgal species, including diatoms and dinoflagellates. Our results highlight an inter- and intraspecific variability of MAG profile in the selected strains. Among them, Skeletonema marinoi (strain FE7) has emerged as the most promising source for possible biotechnological production of MAGs. Full article

Serotonin transporter (SERT) deficiency has been implicated in metabolic syndrome, intestinal inflammation, and microbial dysbiosis. Interestingly, changes in microbiome metabolic capacity and several alterations in host gene expression, including lipid metabolism, were previously observed in SERT^−/− mice ileal mucosa. However, the precise host or microbial metabolites altered by SERT deficiency that may contribute to the pleiotropic phenotype of SERT KO mice are not yet understood. This study investigated the hypothesis that SERT deficiency impacts lipid and microbial metabolite abundances in the ileal mucosa, where SERT is highly expressed. Ileal mucosal metabolomics was performed by Metabolon on wild-type (WT) and homozygous SERT knockout (KO) mice. Fluorescent-activated cell sorting (FACS) was utilized to measure immune cell populations in ileal lamina propria to assess immunomodulatory effects caused by SERT deficiency. SERT KO mice exhibited a unique ileal mucosal metabolomic signature, with the most differentially altered metabolites being lipids. Such changes included increased diacylglycerols and decreased monoacylglycerols in the ileal mucosa of SERT KO mice compared to WT mice. Further, the ileal mucosa of SERT KO mice exhibited several changes in microbial-related metabolites known to play roles in intestinal inflammation and insulin resistance. SERT KO mice also had a significant reduction in the abundance of ileal group 3 innate lymphoid cells (ILC3). In conclusion, SERT deficiency induces complex alterations in the ileal mucosal environment, indicating potential links between serotonergic signaling, gut microbiota, mucosal immunity, intestinal inflammation, and metabolic syndrome. Full article

Drying is an inseparable part of industrial microalgae production. In this work, the impacts of eight different drying methods on the metabolome and lipidome of Arthrospira platensis were investigated. The studied drying methods were freeze drying (FD), sun drying (SD), air drying at 40 and 75 °C (AD′ and AD″), infrared drying at 40 and 75 °C (IRD′ and IRD″), and vacuum drying at 40 and 75 °C (VD′ and VD″). Results gathered by reversed-phase liquid chromatography separation coupled with high-resolution tandem mass spectrometry with electrospray ionization (RP-LC-ESI-Orbitrap HRMS/MS) analysis allowed researchers to identify a total of 316 metabolites (including lipids) in aqueous and ethanolic extracts. The compounds identified in ethanolic extracts were mainly lipids, such as neutral and polar lipids, chlorophylls and carotenoids, while the compounds identified in the aqueous extracts were mainly amino acids and dipeptides. Among the identified compounds, products of enzymatic and chemical degradation, such as pyropheophytins, monoacylglycerols and lysophosphatidylcholines were also identified and their amounts depended on the drying method. The results showed that except for FD method, recognized as a control, the most protective method was AD′. Contrary to this, VD′ and VD″, under the conditions used, promoted the most intense degradation of valuable metabolites. Full article

Alzheimer’s disease (AD), the most common neurodegenerative disease (NDD), is characterized by chronic neuronal cell death through progressive loss of cognitive function. Amyloid beta (Aβ) deposition, neuroinflammation, oxidative stress, and hyperphosphorylated tau proteins are considered the hallmarks of AD pathology. Different therapeutic approaches approved by the Food and Drug Administration can only target a single altered pathway instead of various mechanisms that are involved in AD pathology, resulting in limited symptomatic relief and almost no effect in slowing down the disease progression. Growing evidence on modulating the components of the endocannabinoid system (ECS) proclaimed their neuroprotective effects by reducing neurochemical alterations and preventing cellular dysfunction. Recent studies on AD mouse models have reported that the inhibitors of the fatty acid amide hydrolase (FAAH) and monoacylglycerol (MAGL), hydrolytic enzymes for N-arachidonoyl ethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), respectively, might be promising candidates as therapeutical intervention. The FAAH and MAGL inhibitors alone or in combination seem to produce neuroprotection by reversing cognitive deficits along with Aβ-induced neuroinflammation, oxidative responses, and neuronal death, delaying AD progression. Their exact signaling mechanisms need to be elucidated for understanding the brain intrinsic repair mechanism. The aim of this review was to shed light on physiology and pathophysiology of AD and to summarize the experimental data on neuroprotective roles of FAAH and MAGL inhibitors. In this review, we have also included CB1R and CB2R modulators with their diverse roles to modulate ECS mediated responses such as anti-nociceptive, anxiolytic, and anti-inflammatory actions in AD. Future research would provide the directions in understanding the molecular mechanisms and development of new therapeutic interventions for the treatment of AD. Full article

Central and peripheral mechanisms of the endocannabinoid system (ECS) favor energy intake and storage. The ECS, especially cannabidiol (CBD) receptors, controls adipocyte differentiation (hyperplasia) and lipid accumulation (hypertrophy) in adipose tissue. In white adipose tissue, cannabidiol receptor 1 (CB1) stimulation increases lipogenesis and inhibits lipolysis; in brown adipose tissue, it decreases mitochondrial thermogenesis and biogenesis. This study compared the availability of phytocannabinoids [CBD and Δ9-tetrahydrocannabinol (THC)] and polyunsaturated fatty acids [omega 3 (ω3) and omega 6 (ω6)] in different hemp seed oils (HSO). The study also examined the effect of HSO on adipocyte lipid accumulation by suppressing cannabinoid receptors in adipogenesis-stimulated human mesenchymal stem cells (hMSCs). Most importantly, Oil-Red-O′ and Nile red tests showed that HSO induced adipogenic hMSC differentiation without differentiation agents. Additionally, HSO-treated cells showed increased peroxisome proliferator-activated receptor gamma (PPARγ) mRNA expression compared to controls (hMSC). HSO reduced PPARγ mRNA expression after differentiation media (DM) treatment. After treatment with HSO, DM-hMSCs had significantly lower CB1 mRNA and protein expressions than normal hMSCs. HSO treatment also decreased transient receptor potential vanilloid 1 (TRPV1), fatty acid amide hydrolase (FAAH), and monoacylglycerol lipase (MGL) mRNAs in hMSC and DM-hMSCs. HSO treatment significantly decreased CB1, CB2, TRPV1, and G-protein-coupled receptor 55 (GPCR55) protein levels in DM-hMSC compared to hMSC in western blot analysis. In this study, HSO initiated adipogenic differentiation in hMSC without DM, but it suppressed CB1 gene and protein expression, potentially decreasing adipocyte lipid accumulation and lipogenic enzymes. Full article

This study investigates the impact of SCs consumption by assessing the effects of three novel synthetic cannabinoids (SCs); MDMB-CHMINACA, 5F-ADB-PINACA, and APICA post-drug treatment. SCs are known for their rapid onset (<1 min) and prolonged duration (≥5 h). Therefore, this research aimed to assess behavioral responses and their correlation with endocannabinoids (ECs) accumulation in the hippocampus, and EC’s metabolic enzymes alteration at different timeframes (1-3-5-h) following drug administration. Different extents of locomotive disruption and sustained anxiety-like symptoms were observed throughout all-encompassing timeframes of drug administration. Notably, MDMB-CHMINACA induced significant memory impairment at 1 and 3 h. Elevated levels of anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) were detected 1 h post-MDMB-CHMINACA and 5F-ADB-PINACA administration. Reduced mRNA expression levels of fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL) (AEA and 2-AG degrading enzymes, respectively), and brain-derived neurotrophic factor (BDNF) occurred at 1 h, with FAAH levels remaining reduced at 3 h. These findings suggest a connection between increased EC content and decreased BDNF expression following SC exposure. Cognitive disruption, particularly motor coordination decline and progressive loss manifested in a time-dependent manner across all the analyzed SCs. Our study highlights the importance of adopting a temporal framework when assessing the effects of SCs. Full article

Bioglycerol is a major by-product of the biodiesel manufacturing process. Various chemical derivatives from bioglycerol would enhance its economic value. An antifreeze of glycerine acetate was chemically converted from an esterification reaction of bioglycerol with acetic acid. The photocatalyst TiO₂/SO₄²⁻ irradiated with ultraviolet light assisted the chemical conversion reaction. The molar ratio of acetic acid/bioglycerol was varied to obtain the optimum composition of the derived antifreeze product. Different cosolvents were considered to enhance the homogeneous extent between the antifreeze of glycerine acetate and biodiesel, and thus, the anti-freezing effect. The cosolvent/glycerine acetate, at various volumetric ratios from 0 to 0.25 vol.%, was blended into a commercial biodiesel. After 5 vol.% antifreeze of the glycerine acetate/cosolvent mixture of the biodiesel was added to the commercial biodiesel, the fuel properties of the biodiesel were analyzed. The effects of the cosolvent types and the blended volumetric ratio of cosolvent to the antifreeze of glycerine acetate on the fuel properties of the commercial biodiesel were analyzed to determine the optimum cosolvent type and volumetric composition of the cosolvent/glycerine acetate. The experimental results show that the antifreeze of glycerine acetate produced from the reaction of acetic acid/glycerol at a molar ratio equal to 8 under UV-light irradiation appeared to have the lowest freezing point. The UV-light irradiation on the TiO₂/SO₄²⁻ catalyst also caused higher triacylglycerol (TAG) and diacylglycerol (DAG) and lower monoacylglycerol (MAG) formation. In addition, the low-temperature fluidity was the most excellent when the volumetric percentage of the methanol/glycerine acetate was equal to 0.25 vol.%, at which the cold filter plugging point (CFPP) of the biodiesel was reduced from 3 °C for the neat biodiesel to −2 °C for the biodiesel blended with the mixture. In contrast, the effect of adding the antifreeze on the CFPP of the biodiesel was inferior; it was reduced from 3 °C for the neat biodiesel to 1 °C for the biodiesel when butanol cosolvent was added. The increase in the volumetric ratio of cosolvent/antifreeze increased the acid value and cetane index while it decreased the kinematic viscosity and CFPP. The heating value was observed to increase for butanol while decreasing for methanol with the increase in the volumetric ratio of cosolvent/antifreeze. In comparison to butanol, the cosolvent methanol caused a higher cetane index and acid value but a lower kinematic viscosity, heating value, and CFPP of the blended commercial biodiesel. Full article

Parkinson’s disease (PD) is a common neurodegenerative disorder with a prolonged prodromal phase. Higher urinary bis(monoacylglycerol)phosphate (BMP) levels associate with LRRK2 (leucine-rich repeat kinase 2) and GBA1 (glucocerebrosidase) mutations, and are considered as potential noninvasive biomarkers for predicting those mutations and PD progression. However, their reliability has been questioned, with inadequately investigated genetics, cohorts, and population. In this study, multiple statistical hypothesis tests were employed on urinary BMP levels and sequences of 90 PD-risk single nucleotide polymorphisms (SNPs) from Parkinson’s Progression Markers Institution (PPMI) participants. Those SNPs were categorized into four groups based on their impact on BMP levels in various cohorts. Variants rs34637584 ^G/A and rs34637584 ^A/A (LRRK2 G2019S) were identified as the most relevant on increasing urinary BMP levels in the PD cohort. Meanwhile, rs76763715 ^T/T (GBA1) was the primary factor elevating BMP levels in the prodromal cohort compared to its T/C and C/C variants (N370S) and the PD cohort. Proteomics analysis indicated the changed transport pathways may be the reasons for elevated BMP levels in prodromal patients. Our findings demonstrated that higher urinary BMP levels alone were not reliable biomarkers for PD progression or gene mutations but might serve as supplementary indicators for early diagnosis and treatment. Full article

Human milk lipids generally have the maximum long-chain fatty acids at the sn-2 position of the glycerol backbone. This positioning makes them more digestible than long-chain fatty acids located at the sn-1, 3 positions. These unique fatty acid distributions are not found elsewhere in nature. When lactation is insufficient, infant formula milk has been used as a substitute. However, the distribution of most fatty acids ininfant formula milk is still different from human milk. Therefore, structured lipids were produced by the redistribution of medium-chain fatty acids from commercial butterfat (CBF) and n-3 and n-6 long-chain fatty acids from skipjack tuna eyeball oil (STEO). Redistribution was carried out via transesterification facilitated by Asian seabass liver lipase (ASL-L). Under the optimum conditions including a CBF/STEO ratio (3:1), transesterification time (60 h), and ASL-L unit (250 U), the newly formed modified-STEO (M-STEO) contained 93.56% triacylglycerol (TAG), 0.31% diacylglycerol (DAG), and 0.02% monoacylglycerol (MAG). The incorporated medium-chain fatty acids accounted for 18.2% of M-STEO, whereas ASL-L could incorporate 40% of n-3 fatty acids and 25–30% palmitic acid in M-STEO. The ¹H NMRA and ¹³CNMR results revealed that the major saturated fatty acid (palmitic acid) and unsaturated fatty acids (DHA and EPA) were distributed at the sn-2 position of the TAGs in M-STEO. Thus, M-STEO enriched with medium-chain fatty acids and n-3 fatty acids positioned at the sn-2 position of TAGs can be a potential substitute for human milk fatty acids in infant formula milk (IFM). Full article

We studied whether the function of presynaptic inhibitory cannabinoid CB₁ receptors on the sympathetic nerve fibres innervating resistance vessels is increased in spontaneously hypertensive rats (SHR) like in deoxycorticosterone (DOCA)–salt hypertension. An increase in diastolic blood pressure (DBP) was induced by electrical stimulation of the preganglionic sympathetic neurons or by phenylephrine injection in pithed SHR and normotensive Wistar–Kyoto rats (WKY). The electrically (but not the phenylephrine) induced increase in DBP was inhibited by the cannabinoid receptor agonist CP55940, similarly in both groups, and by the endocannabinoid reuptake inhibitor AM404 in SHR only. The effect of CP55940 was abolished/reduced by the CB₁ receptor antagonist AM251 (in both groups) and in WKY by endocannabinoid degradation blockade, i.e., the monoacylglycerol lipase (MAGL) inhibitor MJN110 and the dual fatty acid amide hydrolase (FAAH)/MAGL inhibitor JZL195 but not the FAAH inhibitor URB597. MJN110 and JZL195 tended to enhance the effect of CP55940 in SHR. In conclusion, the function of presynaptic inhibitory CB₁ receptors depends on the hypertension model. Although no differences occurred between SHR and WKY under basal experimental conditions, the CB₁ receptor function was better preserved in SHR when the endocannabinoid tone was increased by the inhibition of MAGL or the endocannabinoid transporter. Full article

Biomarkers are molecules that can be used to observe changes in an individual’s biochemical or medical status and provide information to aid diagnosis or treatment decisions. Dysregulation in lipid metabolism in the brain is a major risk factor for many neurodegenerative disorders, including frontotemporal dementia, Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Thus, there is a growing interest in using lipids as biomarkers in neurodegenerative diseases, with the anionic phospholipid bis(monoacylglycerol)phosphate and (glyco-)sphingolipids being the most promising lipid classes thus far. In this review, we provide a general overview of lipid biology, provide examples of abnormal lysosomal lipid metabolism in neurodegenerative diseases, and discuss how these insights might offer novel and promising opportunities in biomarker development and therapeutic discovery. Finally, we discuss the challenges and opportunities of lipid biomarkers and biomarker panels in diagnosis, prognosis, and/or treatment response in the clinic. Full article

Lipases are enzymes that catalyze the hydrolysis of ester bonds of triacylglycerols at the oil–water interface, generating free fatty acids, glycerol, diacylglycerol, and monoacylglycerol, which can be produced from the fermentation of agro-industrial by-products rich in fatty acids, such as cupuaçu fat cake. In this study, Yarrowia lipolytica IMUFRJ50682 was used for lipase production from cupuaçu fat cake in solid-state fermentation (SSF) associated with soybean meal. The 2:1 ratio of cupuaçu fat cake/soybean meal increased the lipase activity of Y. lipolytica via SSF by approximately 30.3-fold compared to that in cupuaçu without supplementation. The optimal conditions for Y. lipolytica to produce lipase were obtained by supplementation with peptone, urea, and soybean oil (all at 1.5% w/v), reaching values of up to 70.6 U g⁻¹. These results demonstrate that cupuaçu fat cake associated with soybean meal can be used for lipase production and adds value to cupuaçu by-products. Furthermore, the proper processing of by-products can contribute to improving the economic viability of the biotechnological processing industry and help prevent the accumulation of waste and environmental pollution. Full article