Search Results (42)

The inflammatory state is a significant factor associated with diabetic kidney disease (DKD), making it one of the significant causes of chronic kidney disease. Despite the availability of data, there is a lack of targeted treatment strategies for diabetes-related kidney disorders. The aim of our study was to determine the impact of cannabigerol (CBG) on lipid precursors for inflammatory mediators during DKD development. A six-week experiment was conducted on male Wistar rats fed standard (Control) or high-fat high-sucrose (HFHS) diets. For the last 14 days of the experiment (5th and 6th weeks), half of the rats from the Control and HFHS groups intragastrically received CBG solution. Gas–liquid chromatography (GLC) was used to measure the activities of n-6 and n-3 polyunsaturated fatty acid (PUFA) metabolic pathways and the concentrations of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) in selected lipid fractions. Immunoblotting was performed to assess the expression of proteins involved in the regulation of the inflammatory state. A multiplex immunoassay kit was used to determine kidney toxicity biomarker levels. Our results revealed that CBG administration to rats fed an HFHS diet decreased n-6 PUFA biosynthetic pathway activity in phospholipid (PL) and triacylglycerol (TAG) and increased n-3 PUFA biosynthetic pathway activity in TAG and free fatty acid (FFA). We also observed a reduction in the AA concentration in PL, FFA, and diacylglycerol (DAG). CBG supplementation reduced the level of kidney damage biomarkers, such as osteopontin (OPN). Our observations confirm that CBG has potential anti-inflammatory properties and may be successfully used for further research to seek targeted therapies of inflammatory disorders, including diabetic kidney disease progression. Full article

Objectives: This study aimed to assess the effects of storage temperature on the lipidomics profile change in Pacific saury (Cololabis saira). Methods: In this paper, C. saira underwent frozen storage at two different temperatures, T1 (−18 °C) and T2 (−25 °C), for a duration of three months. Chemical and lipidomic methods were used to determine the changes in lipids during the storage process. Results: Results showed that the content of triglyceride and phospholipid decreased significantly (p < 0.05), and free fatty acid increased significantly (p < 0.05), while the content of total cholesterol remained relatively constant across different storage temperatures. Additionally, an increasing trend in AV, POV, and TBARS contents was observed after the freezing process, with lipid oxidation being significantly higher in the −18 °C group compared to the −25 °C group (p < 0.05). A comprehensive analysis identified 4854 lipid molecules in the muscles of C. saira, categorized into 46 lipid subclasses, predominantly including triglycerides (TG), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylglycerol (PG), and diglycerides (DG). Among them, TG was the most abundant lipid, followed by PC. Using orthogonal partial least squares discriminant analysis (OPLS-DA) with a variable importance in projection (VIP) score > 1 and p value < 0.05 as criteria, 338, 271, and 103 highly significantly differentiated lipids were detected in the comparison groups CK vs. T1, CK vs. T2, and T1 vs. T2, respectively. The results indicated that storage at −18 °C had a more pronounced effect than storage at −25 °C. During the freezing process, TG expression was significantly down-regulated, and TG(18:4_14:0_20:5), TG(20:5_13:0_22:6), TG(22:6_14:1_22:6), and TG(18:4_13:0_22:6) were the most predominant individuals. The CK group was initially present in C. saira before storage. Differential lipid molecules in the CK vs. T1 and CK vs. T2 groups were screened using a fold change (FC) > 2 or FC < 0.5. In the CK vs. T2 group, 102 highly significant differential lipid molecules were identified, with 55 being down-regulated across seven subclasses. In contrast, the CK vs. T1 group revealed 254 highly significant differential lipid molecules, with 85 down-regulated across 13 subclasses. The results showed that more PCs and PEs were down-regulated, with a higher differential abundance of PE and PC in the −25 °C group compared to the −18 °C group. The differential metabolites were primarily enriched in 17 metabolic pathways, with glycerophospholipid metabolism being the most prominent, followed by sphingolipid metabolism during the frozen storage. Conclusions: Overall, −25 °C storage in production was more favorable for maintaining the lipid stability of C. saira. This work could provide useful information for aquatic product processing and lipidomics. Full article

Polyunsaturated fatty acids such as arachidonic acid are indispensable components of innate immune signaling. Plasmalogens are glycerophospholipids with a vinyl ether bond in the sn-1 position of the glycerol backbone instead of the more common sn-1 ester bond present in “classical” glycerophospholipids. This kind of phospholipid is particularly rich in polyunsaturated fatty acids, especially arachidonic acid. In addition to or independently of the role of plasmalogens as major providers of free arachidonic acid for eicosanoid synthesis, plasmalogens also perform a varied number of functions. Membrane plasmalogen levels may determine parameters of the plasma membrane, such as fluidity and the formation of microdomains that are necessary for efficient signal transduction leading to optimal phagocytosis by macrophages. Also, plasmalogens may be instrumental for the execution of ferroptosis. This is a nonapoptotic form of cell death that is associated with oxidative stress. This review discusses recent data suggesting that, beyond their involvement in the cellular metabolism of arachidonic acid, the cells maintain stable pools of plasmalogens rich in polyunsaturated fatty acids for executing specific responses. Full article

Phospholipids and their metabolites play an important role in maintaining the membrane integrity and the metabolic functions of keratinocytes under physiological conditions and in the regeneration process after exposure to high-energy UVB radiation. Therefore, in the search for compounds with a protective and regenerative effect on keratinocyte phospholipids, the effectiveness of two antioxidant compounds has been tested: a stable derivative of ascorbic acid, 3-O-ethyl ascorbic acid (EAA) and cannabigerol (CBG), both of which are primarily located in the membrane structures of keratinocytes. In addition, this study has demonstrated that EAA and CBG, especially in a two-component combination, enhance the antioxidant properties of keratinocytes and reduce lipid peroxidation assessed at the level of MDA (malondialdehyde)/neuroprostanes. Moreover, by reducing the activity of enzymes that metabolise phospholipids, free PUFAs (polyunsaturated fatty acids) and endocannabinoids (PLA2; phospholipase A2, COX1/2; cyclooxygenases 1/2, LOX-5; lipoxygenase 5, FAAH; fatty acid amide hydrolase, MAGL; monoacylglycerol lipase), antioxidants have been found to regulate the levels of endocannabinoids (AEA; anandamide, 2-AG; 2-arachidonoylglycerol, PEA; palmitoylethanolamide) and eicosanoids (PGD2; prostaglandin D2, PGE2; prostaglandin E2, 15-d-PGJ2; 15-deoxy-Δ12,14-prostaglandin J2, 15-HETE; 15-hydroxyeicosatetraenoic acid), that are enhanced by UVB radiation. The metabolic effect of both groups of PUFA metabolites is mainly related to the activation of G protein-related receptors (CB1/2; cannabinoid receptor 1 and 2, PPARγ; peroxisome proliferator-activated receptor gamma, TRPV1; transient receptor potential cation channel subfamily V member 1), the expression of which is reduced under the influence of EAA, CBG, and especially the two-component combination. It promotes the regeneration of keratinocyte metabolism disrupted by UVB, particularly in relation to redox balance and inflammation. Full article

The Lueyang black-bone chicken is a specific native chicken strain in China. This study aimed to investigate the effects of different rearing systems on the meat quality of Lueyang black-bone chickens. Six hundred Lueyang black-bone hens were randomly divided into two groups at 7 weeks of age and raised in cage and cage-free systems for 20 weeks. The carcass yield, meat quality, and total metabolites were measured in both the leg and breast muscles. By comparison, the carcass yield of hens in the cage-free (CF) group (1.26 ± 0.09 kg) was significantly lower than that in the caged rearing (CR) group (1.52 ± 0.15 kg). However, the shear force of leg muscles in the CF group (27.98 ± 2.43 N) was significantly greater than that in the CR group (24.15 ± 1.93 N). In addition, six samples from each group were randomly selected and their metabolites were detected by the non-targeted metabolomics technique. Among these metabolites, 408 and 354 significantly differentially abundant metabolites were identified in breast and leg muscles, which were mainly involved in glycerophospholipid metabolism, unsaturated fatty acid biosynthesis, arginine and proline metabolism, and nucleotide metabolism. We found that the levels of 19 phospholipids, mainly phosphatidylcholines and lysophosphatidylcholines, were significantly greater in the CF group than in the CR group. Additionally, the contents of eight unsaturated fatty acids, linoleic acid, and linolenic acid were dramatically greater in the CF group than in the caged group. The accumulation of 4-hydroxy-proline, glutamate, and adenosine 3′-monophosphate (AMP) was enhanced in the CF group. Moreover, many more volatile organic compounds were identified in the muscles of the cage-free group, enhancing the flavor of the chicken meat. In conclusion, the cage-free rearing mode facilitates the accumulation of nutrients and flavor substances in the chicken meat and is a better rearing system for Lueyang black-bone chickens. Full article

Brain lipid homeostasis is an absolute requirement for proper functionality of nerve cells and neurological performance. Current evidence demonstrates that lipid alterations are linked to neurodegenerative diseases, especially Alzheimer’s disease (AD). The complexity of the brain lipidome and its metabolic regulation has hampered the identification of critical processes associated with the onset and progression of AD. While most experimental studies have focused on the effects of known factors on the development of pathological hallmarks in AD, e.g., amyloid deposition, tau protein and neurofibrillary tangles, neuroinflammation, etc., studies addressing the causative effects of lipid alterations remain largely unexplored. In the present study, we have used a multifactor approach combining diets containing different amounts of polyunsaturated fatty acids (PUFAs), estrogen availabilities, and genetic backgrounds, i.e., wild type (WT) and APP/PS1 (FAD), to analyze the lipid phenotype of the frontal cortex in middle-aged female mice. First, we observed that severe n-3 PUFA deficiency impacts the brain n-3 long-chain PUFA (LCPUFA) composition, yet it was notably mitigated by hepatic de novo synthesis. n-6 LCPUFAs, ether-linked fatty acids, and saturates were also changed by the dietary condition, but the extent of changes was dependent on the genetic background and hormonal condition. Likewise, brain cortex phospholipids were mostly modified by the genotype (FAD>WT) with nuanced effects from dietary treatment. Cholesterol (but not sterol esters) was modified by the genotype (WT>FAD) and dietary condition (higher in DHA-free conditions, especially in WT mice). However, the effects of estrogen treatment were mostly observed in relation to phospholipid remodeling in a genotype-dependent manner. Analyses of lipid-derived variables indicate that nerve cell membrane biophysics were significantly affected by the three factors, with lower membrane microviscosity (higher fluidity) values obtained for FAD animals. In conclusion, our multifactor analyses revealed that the genotype, diet, and estrogen status modulate the lipid phenotype of the frontal cortex, both as independent factors and through their interactions. Altogether, the outcomes point to potential strategies based on dietary and hormonal interventions aimed at stabilizing the brain cortex lipid composition in Alzheimer’s disease neuropathology. Full article

There is a “popular” belief that a fat-free diet is beneficial, supported by the scientific dogma indicating that high levels of fatty acids promote many pathological metabolic, cardiovascular, and neurodegenerative conditions. This dogma pressured scientists not to recognize the essential role of fatty acids in cellular metabolism and focus on the detrimental effects of fatty acids. In this work, we critically review several decades of studies and recent publications supporting the critical role of mitochondrial fatty acid metabolism in cellular homeostasis and many pathological conditions. Fatty acids are the primary fuel source and essential cell membrane building blocks from the origin of life. The essential cell membranes phospholipids were evolutionarily preserved from the earlier bacteria in human subjects. In the past century, the discovery of fatty acid metabolism was superseded by the epidemic growth of metabolic conditions and cardiovascular diseases. The association of fatty acids and pathological conditions is not due to their “harmful” effects but rather the result of impaired fatty acid metabolism and abnormal lifestyle. Mitochondrial dysfunction is linked to impaired metabolism and drives multiple pathological conditions. Despite metabolic flexibility, the loss of mitochondrial fatty acid oxidation cannot be fully compensated for by other sources of mitochondrial substrates, such as carbohydrates and amino acids, resulting in a pathogenic accumulation of long-chain fatty acids and a deficiency of medium-chain fatty acids. Despite popular belief, mitochondrial fatty acid oxidation is essential not only for energy-demanding organs such as the heart, skeletal muscle, and kidneys but also for metabolically “inactive” organs such as endothelial and epithelial cells. Recent studies indicate that the accumulation of long-chain fatty acids in specific organs and tissues support the impaired fatty acid oxidation in cell- and tissue-specific fashion. This work, therefore, provides a basis to challenge these established dogmas and articulate the need for a paradigm shift from the “pathogenic” role of fatty acids to the critical role of fatty acid oxidation. This is important to define the causative role of impaired mitochondrial fatty acid oxidation in specific pathological conditions and develop novel therapeutic approaches targeting mitochondrial fatty acid metabolism. Full article

In this study, serum metabolic profiling of patients diagnosed with papillary thyroid carcinoma (PTC) and benign thyroid pathologies (BT) aimed to identify specific biomarkers and altered pathways when compared with healthy controls (C). The blood was collected after a histological confirmation from PTC (n = 24) and BT patients (n = 31) in parallel with healthy controls (n = 81). The untargeted metabolomics protocol was applied by UHPLC-QTOF-ESI⁺-MS analysis and the statistical analysis was performed using the MetaboAnalyst 5.0 platform. The partial least squares-discrimination analysis, including VIP values, random forest graphs, and heatmaps (p < 0.05), was complemented with biomarker analysis (with AUROC ranking) and pathway analysis, suggesting a model for abnormal metabolic pathways in PTC and BT based on 166 identified metabolites. There were 11 classes of putative biomarkers selected that were involved in altered metabolic pathways, e.g., polar molecules (amino acids and glycolysis metabolites, purines and pyrimidines, and selenium complexes) and lipids including free fatty acids, bile acids, acylated carnitines, corticosteroids, prostaglandins, and phospholipids. Specific biomarkers of discrimination were identified in each class of metabolites and upregulated or downregulated comparative to controls, PTC group, and BT group. The lipidomic window was revealed to be more relevant for finding biomarkers related to thyroid carcinoma or benign thyroid nodules, since our study reflected a stronger involvement of lipids and selenium-related molecules in metabolic discrimination. Full article

UVA radiation leads to oxidative stress and inflammation in skin cells. Therefore, the aim of this study was to compare the effect of lipid extracts from microalgae Nannochloropsis oceanica (N.o.) (marine) and Chlorococcum amblystomatis (C.a.) (freshwater) on the redox balance and PUFA metabolism in human skin fibroblasts modified by UVA. Lipid extracts from both types of microalgae introduced into the fibroblast medium after UVA irradiation significantly reduced the level of ROS and enhanced expression of Nrf2, which increased the activity/level of antioxidants (SOD1/2, CAT, GSH, Trx). The reduction in oxidative stress was accompanied by a decrease in the level of 4-HNE, its protein adducts and protein carbonyl groups. Microalgae also reduced the activity of COX1/2, FAAH and MAGL increased by UVA, and as a consequence, the level of lipid mediators (especially after N.o.) decreased, both from the group of endocannabinoids (AEA, 2-AG, PEA) and eicosanoids (PGE2, 15d-PGJ2, TXB2, 15-HETE), acting mainly through receptors related to G protein, the expression of which increases after UVA. This further contributed to the reduction in oxidative stress and pro-inflammatory signaling at NF-κB and TNFα levels. Therefore, it is suggested that lipid extracts from both N.o. and C.a. microalgae can be used to regenerate fibroblast metabolism disturbed by UVA radiation. Full article

Ultraviolet B (UVB) radiation induces oxidative stress in skin cells, generating reactive oxygen species (ROS) and perturbing enzyme-mediated metabolism. This disruption is evidenced with elevated concentrations of metabolites that play important roles in the modulation of redox homeostasis and inflammatory responses. Thus, this research sought to determine the impacts of the lipid extract derived from the Nannochloropsis oceanica microalgae on phospholipid metabolic processes in keratinocytes subjected to UVB exposure. UVB-irradiated keratinocytes were treated with the microalgae extract. Subsequently, analyses were performed on cell lysates to ascertain the levels of phospholipid/free fatty acids (GC-FID), lipid peroxidation byproducts (GC-MS), and endocannabinoids/eicosanoids (LC-MS), as well as to measure the enzymatic activities linked with phospholipid metabolism, receptor expression, and total antioxidant status (spectrophotometric methods). The extract from N. oceanica microalgae, by diminishing the activities of enzymes involved in the synthesis of endocannabinoids and eicosanoids (PLA2/COX1/2/LOX), augmented the concentrations of anti-inflammatory and antioxidant polyunsaturated fatty acids (PUFAs), namely DHA and EPA. These concentrations are typically diminished due to UVB irradiation. As a consequence, there was a marked reduction in the levels of pro-inflammatory arachidonic acid (AA) and associated pro-inflammatory eicosanoids and endocannabinoids, as well as the expression of CB1/TRPV1 receptors. The microalgal extract also mitigated the increase in lipid peroxidation byproducts, specifically MDA in non-irradiated samples and 10-F4t-NeuroP in both control and post-UVB exposure. These findings indicate that the lipid extract derived from N. oceanica, by mitigating the deleterious impacts of UVB radiation on keratinocyte phospholipids, assumed a pivotal role in reinstating intracellular metabolic equilibrium. Full article

Type 2 diabetes mellitus (T2DM) leads to the development of cardiovascular diseases, cognitive impairment, and dementia. There are sex differences in the presentation of T2DM and its associated complications. We sought to determine the impact of sex and T2DM on the brain metabolome to gain insights into the underlying mechanisms of T2DM-associated cognitive complications. Untargeted metabolomic analysis was performed, using liquid chromatography-mass spectrometry, on whole brain tissue from adult male and female db/db mice (a T2DM model) compared to wild-type (WT) C57Bl6/J mice. Regardless of sex, T2DM increased free fatty acids and decreased acylcarnitines in the brain. Sex impacted the number (103 versus 65 in males and females, respectively), and types of metabolites shifted by T2DM. Many choline-containing phospholipids were decreased by T2DM in males. Female-specific T2DM effects included changes in neuromodulatory metabolites (γ-aminobutyric acid, 2-linoleoyl glycerol, N-methylaspartic acid, and taurine). Further, there were more significantly different metabolites between sexes in the T2DM condition as compared to the WT controls (54 vs. 15 in T2DM and WT, respectively). T2DM alters the murine brain metabolome in both sex-independent and sex-dependent manners. This work extends our understanding of brain metabolic sex differences in T2DM, cognitive implications, and potential sex-specific metabolic therapeutic targets. Full article

Cell function and energy redistribution are influenced by lipid classes (phospholipids (PLs), free fatty acids (FFAs), triglycerides (TGs), and cholesterol esters (CEs)). The aim of this study was to investigate metabolic alterations that are related to changes in lipid classes according to different levels of energy deficits in early lactating Mediterranean buffaloes (MBs). Sixty-three MBs were enrolled at the beginning of lactation using an observational study with a cross-sectional experimental design. Serum β-hydroxybutyrate (BHB) levels were used to group the animals into a healthy group (Group H; n = 38; BHB < 0.70 mmol/L) and hyperketonemia risk group (Group K; n = 25; BHB ≥ 0.70 mmol/L). Statistical analysis was performed using a linear model that included the effect of the group and body condition score to assess differences in fatty acid (FA) concentrations. A total of 40 plasma FAs were assessed in each lipid class. Among the FAs, eight PLs, seven FFAs, four TGs, and four CEs increased according to BHB levels, while three FFAs, three TGs, and one CE decreased. The changes among lipid class profiles suggested the influence of inflammatory response, liver metabolism, and the state of body lipid reserves. In addition, the possible similarities of buffaloes at risk of hyperketonemia with ketotic cows suggest the necessity of further investigations in these ruminants. Full article

Mitochondria interact with the endoplasmic reticulum (ER) through contacts called mitochondria-associated membranes (MAMs), which control several processes, such as the ER stress response, mitochondrial and ER dynamics, inflammation, apoptosis, and autophagy. MAMs represent an important platform for transport of non-vesicular phospholipids and cholesterol. Therefore, this region is highly enriched in proteins involved in lipid metabolism, including the enzymes that catalyze esterification of cholesterol into cholesteryl esters (CE) and synthesis of triacylglycerols (TAG) from fatty acids (FAs), which are then stored in lipid droplets (LDs). LDs, through contact with other organelles, prevent the toxic consequences of accumulation of unesterified (free) lipids, including lipotoxicity and oxidative stress, and serve as lipid reservoirs that can be used under multiple metabolic and physiological conditions. The LDs break down by autophagy releases of stored lipids for energy production and synthesis of membrane components and other macromolecules. Pathological lipid deposition and autophagy disruption have both been reported to occur in several neurodegenerative diseases, supporting that lipid metabolism alterations are major players in neurodegeneration. In this review, we discuss the current understanding of MAMs structure and function, focusing on their roles in lipid metabolism and the importance of autophagy in LDs metabolism, as well as the changes that occur in neurogenerative diseases. Full article

Hepatitis C virus (HCV) is a major human pathogen that requires a better understanding of its interaction with host cells. There is a close association of HCV life cycle with host lipid metabolism. Lipid droplets (LDs) have been found to be crucial organelles that support HCV replication and virion assembly. In addition to their role in replication, LDs also have protein-mediated antiviral properties that are activated during HCV infection. Studies have shown that HCV replicates well in cholesterol and sphingolipid-rich membranes, but the ways in which HCV alters host cell lipid dynamics are not yet known. In this study, we performed a kinetic study to check the enrichment of LDs at different time points of HCV infection. Based on the LD enrichment results, we selected early and later time points of HCV infection for global lipidomic study. Early infection represents the window period for HCV sensing and host immune response while later infection represents the establishment of viral RNA replication, virion assembly, and egress. We identified the dynamic profile of lipid species at early and later time points of HCV infection by global lipidomic study using mass spectrometry. At early HCV infection, phosphatidylinositol phospholipids (PIPs), lysophosphatidic acid (LPA), triacyl glycerols (TAG), phosphatidylcholine (PC), and trihexosylceramides (Hex3Cer) were observed to be enriched. Similarly, free fatty acids (FFA), phosphatidylethanolamine (PE), N-acylphosphatidylethanolamines (NAPE), and tri acylglycerols were enriched at later time points of HCV infection. Lipids enriched at early time of infection may have role in HCV sensing, viral attachment, and immune response as LPA and PIPs are important for immune response and viral attachment, respectively. Moreover, lipid species observed at later infection may contribute to HCV replication and virion assembly as PE, FFA, and triacylglycerols are known for the similar function. In conclusion, we identified lipid species that exhibited dynamic profile across early and later time points of HCV infection compared to mock cells, which could be therapeutically relevant in the design of more specific and effective anti-viral therapies. Full article

A comprehensive chemical characterization of different lipid components, namely fatty acid composition after derivatization in fatty acid methyl esters (FAMEs), triacylglycerols (TAGs), phospholipids (PLs), free fatty acids (FFAs), sterols, carotenoids, tocopherols, and polyphenols in Chia seed oil, obtained by Soxhlet extraction, was reported. Reversed phase liquid chromatography (RP-LC) coupled to UV and mass spectrometry (MS) detectors was employed for carotenoids, polyphenols, and TAGs determination; normal phase-LC in combination with fluorescence detector (FLD) was used for tocopherols analysis; PL and FFA fractions were investigated after a rapid solid phase extraction followed by RP-LC-MS and NanoLC coupled to electron ionization (EI) MS, respectively. Furthermore, gas chromatography (GC)-flame ionization (FID) and MS detectors were used for FAMEs and sterols analysis. Results demonstrated a significant content of bioactive compounds, such as the antioxidant tocopherols (22.88 µg mL⁻¹), and a very high content of essential fatty acids (81.39%), namely α-linolenic (62.16%) and linoleic (19.23%) acids. In addition, for the best of authors knowledge, FFA profile, as well as some carotenoid classes has been elucidated for the first time. The importance of free fatty acids in vegetable matrices is related to the fact that they can be readily involved in metabolic processes or biosynthetic pathways of the plant itself. For a fast and reliable determination of this chemical class, a very innovative and sensitive NanoLC-EI-MS analytical determination was applied. Full article