Lipid Metabolism In Animals Research Articles

The molecular regulated mechanism of METTL3 and FTO in lipid metabolism of Hu sheep

BackgroundBalanced lipid metabolism can improve the growth performance and meat quality of livestock. The m6A methylation-related genes METTL3 and FTO play important roles in animal lipid metabolism; however, the mechanism through which they regulate lipid metabolism in sheep is unclear. ResultsWe established lipid deposition models of hepatocytes and preadipocytes in Hu sheep. In the hepatocyte lipid deposition model, the genes expression levels of FABP4, Accα, ATGL and METTL3, METTL14, and FTO—were significantly up-regulated after lipid deposition (P < 0.05). Transcriptomic and metabolomic analyses showed that lipid deposition had a significant effect on MAPK, steroid biosynthesis, and glycerophospholipid metabolism pathway in hepatocytes. The m6A methylation level decreased but the difference was not significant after METTL3 interference, and the expression levels of FABP4 and ATGL increased significantly (P < 0.05); the m6A methylation level significantly increased following METTL3 overexpression, and LPL and ATGL expression levels significantly decreased (P < 0.05), indicating that overexpression of METTL3 inhibited the expression of lipid deposition-related genes in a m6A-dependent manner. The m6A methylation level was significantly increased, ATGL expression was significantly decreased (P < 0.05), and LPL, FABP4, and Accα expression was not significantly changed following FTO interference (P > 0.05); the m6A methylation level was significantly decreased after FTO overexpression, and LPL, FABP4, and ATGL expression was significantly increased (P < 0.05), indicating that FTO overexpression increased the expression of lipid deposition-related genes in a m6A-dependent manner. Transcriptomic and metabolomic analyses showed that m6A methylation modification mainly regulated lipid metabolism through triglyceride metabolism, adipocytokine signaling, MAPK signaling, and fat digestion and absorption in hepatocytes. In the lipid deposition model of preadipocytes, the regulation of gene expression is the same as that in hepatocytes. ConclusionsMETTL3 significantly inhibited the expression of lipid deposition-related genes, whereas FTO overexpression promoted lipid deposition. Our study provides a theoretical basis and reference for accurately regulating animal lipid deposition by mastering METTL3 and FTO genes to promote high-quality animal husbandry.

LncRNA lncLLM Facilitates Lipid Deposition by Promoting the Ubiquitination of MYH9 in Chicken LMH Cells.

The liver plays an important role in regulating lipid metabolism in animals. This study investigated the function and mechanism of lncLLM in liver lipid metabolism in hens at the peak of egg production. The effect of lncLLM on intracellular lipid content in LMH cells was evaluated by qPCR, Oil Red O staining, and detection of triglyceride (TG) and cholesterol (TC) content. The interaction between lncLLM and MYH9 was confirmed by RNA purification chromatin fractionation (CHIRP) and RNA immunoprecipitation (RIP) analysis. The results showed that lncLLM increased the intracellular content of TG and TC and promoted the expression of genes related to lipid synthesis. It was further found that lncLLM had a negative regulatory effect on the expression level of MYH9 protein in LMH cells. The intracellular TG and TC content of MYH9 knockdown cells increased, and the expression of genes related to lipid decomposition was significantly reduced. In addition, this study confirmed that the role of lncLLM is at least partly through mediating the ubiquitination of MYH9 protein to accelerate the degradation of MYH9 protein. This discovery provides a new molecular target for improving egg-laying performance in hens and treating fatty liver disease in humans.

The role and molecular mechanisms of copper in regulating animal lipid metabolism

The role and molecular mechanisms of copper in regulating animal lipid metabolism

The polyketide to fatty acid transition in the evolution of animal lipid metabolism

Animals synthesize simple lipids using a distinct fatty acid synthase (FAS) related to the type I polyketide synthase (PKS) enzymes that produce complex specialized metabolites. The evolutionary origin of the animal FAS and its relationship to the diversity of PKSs remain unclear despite the critical role of lipid synthesis in cellular metabolism. Recently, an animal FAS-like PKS (AFPK) was identified in sacoglossan molluscs. Here, we explore the phylogenetic distribution of AFPKs and other PKS and FAS enzymes across the tree of life. We found AFPKs widely distributed in arthropods and molluscs (>6300 newly described AFPK sequences). The AFPKs form a clade with the animal FAS, providing an evolutionary link bridging the type I PKSs and the animal FAS. We found molluscan AFPK diversification correlated with shell loss, suggesting AFPKs provide a chemical defense. Arthropods have few or no PKSs, but our results indicate AFPKs contributed to their ecological and evolutionary success by facilitating branched hydrocarbon and pheromone biosynthesis. Although animal metabolism is well studied, surprising new metabolic enzyme classes such as AFPKs await discovery.

Conducting biological tests in the development of self-emulsifying drug delivery systems with simvastatin

The aim of the study was to compare the hypolipidemic activity of the developed self-emulsifying drug delivery systems with simvastatin with reference samples of the substance and the finished drug product of industrial production. Materials and methods. The substance of simvastatin (India, s. DK40-2005021, 99.09 %, introduced into the composition of self-emulsifying compositions based on castor oil (Ukraine), polyethylene glycol 40 hydrogenated castor oil (India), Tween 80 (Ukraine), glycerol monostearate (Gustav Heess GmbH, Germany) or polyethylene glycol 100 stearate (ERCA, Italy). Reference samples were Simvastatin-Sandoz (Salutas Pharma, Germany, series LX5161) and simvastatin in pure form. The experimental animals were Syrian hamsters aged 2 months. Hyperlipidemia was modeled by means of an alimentary load. To assess the state of lipid metabolism in animals, the content of triacylglycerols, total cholesterol, low-density lipoprotein and high-density lipoprotein in the blood serum was determined by colorimetric enzymatic methods using the appropriate standard reagent kits "Triacylglycerols F" HP022.02, "Cholesterol F" HP026.02, "Cholesterol-LDL F" HP026.05 and "Cholesterol-HDL F" HP026.04 (LLC SPE "Filicit-Diagnostics", Ukraine) on a semi-automatic biochemical analyzer MapLab Plus (BSI, Italy). Results. The reference samples had similar dose-dependent efficacy parameters. At the same time, the test samples, also having similar dose-dependent effects, in absolute terms at the maximum concentration reduced the amount of low-density lipoprotein and total cholesterol more effectively than the reference samples. When using the test samples in their average concentration, the level of triglycerols was significantly reduced, which is rather a concomitant effect of simvastatin. Conclusions. The improvement of the overall efficacy of simvastatin when it is introduced into self-emulsifying drug delivery systems has been proved, which is associated with the modification of pharmacokinetic parameters by improving the solubility of the substance in the aqueous environment of the gastrointestinal tract

Jatobá-do-cerrado (Hymenaea stigonocarpa Mart.) pulp positively affects plasma and hepatic lipids and increases short-chain fatty acid production in hamsters fed a hypercholesterolemic diet

This study aimed to assess the impact of jatobá pulp, in its fresh (FJ) and extruded (EJ) forms, on lipid metabolism and intestinal fermentation parameters in hamsters. In a 21-day experiment, we determined the parameters of the animal lipid metabolism and colonic production of short chain fatty acids in four different groups. Control (C), fresh pulp (FJ) and extruded pulp (EJ) were fed using hypercholesterolemic diets, and the reference (R) was fed using AIN93 meal. R and C diets contained cellulose, FJ and EJ were added by jatobá pulp as a fiber source. The results showed that FJ and EJ exhibited lower levels of triglycerides, total cholesterol, LDL-c, non-HDL-c serum levels, liver lipids, and liver weight compared to C. The EJ had higher bile acid excretion in stool than the C. EJ and FJ exhibited lower excreted fiber compared to R and C, implying greater fermentation. Furthermore, the production of short-chain fatty acids (SCFA) in the cecum of FJ and EJ animals exceeded that of the C. Acetic and propionic acids were more abundant in the FJ and EJ diets, with FJ producing more butyric acid than the other groups.In conclusion, jatobá pulp maintained at normal levels of total cholesterol, LDL and HDL-associated cholesterol, non-HDL cholesterol, and serum triglycerides, while also reducing the accumulation of hepatic lipids. Jatobá also promoted SCFA formation and fermentation, making it a valuable ingredient for preventing chronic diseases.

Impacts of polypropylene microplastics on lipid profiles of mouse liver uncovered by lipidomics analysis and Raman spectroscopy

Microplastics (MPs) are emerging contaminants, and there are only limited studies reporting the impacts of some MPs on liver lipid metabolism in animals. In this study, we investigated the accumulation of polypropylene-MPs in mouse liver and unraveled the change in lipid metabolic profiles by both lipidomics and Raman spectroscopy. Polypropylene-MP exposure did not cause obvious health symptoms, but hematoxylin-eosin staining showed pathological changes that polypropylene-MPs induced lipid droplet accumulation in liver. Lipidomics results showed a significant change in lipid metabolic profiles and the most influenced categories were triglycerides, fatty acids, free fatty acids and lysophosphatidylcholine, implying the effects of polypropylene-MPs on the hemostasis of lipid droplet biogenesis and catabolism. Most altered lipids contained unsaturated bonds and polyunsaturated phospholipids, possibly affecting the fluidity and curvature of membrane surfaces. Raman spectroscopy confirmed that the major spectral alterations of liver tissues were related to lipids, evidencing the altered lipid metabolism and cell membrane components in the presence of polypropylene-MPs. Our findings firstly disclosed the impacts of polypropylene-MPs on lipid metabolisms in mouse liver and hinted at their detrimental disturbance on membrane properties, cellular lipid storage and oxidation regulation, helping our deeper understanding on the toxicities and corresponding risks of polypropylene-MPs to mammals.

Interaction between gut microbiota metabolites and dietary components in lipid metabolism and metabolic diseases.

Gut microbiota composition has caused perplexity in developing precision therapy to cure metabolic disorders. However, recent research has focused on using daily diet and natural bioactive compounds to correct gut microbiota dysbiosis and regulate host metabolism. Complex interactions between the gut microbiota and dietary compounds disrupt or integrate the gut barrier and lipid metabolism. In this review, we investigate the role of diet and bioactive natural compounds in gut microbiota dysbiosis and also the modulation of lipid metabolism by their metabolites. Recent studies have revealed that diet, natural compounds and phytochemicals impact significantly on lipid metabolism in animals and humans. These findings suggest that dietary components or natural bioactive compounds have a significant impact on microbial dysbiosis linked to metabolic diseases. The interaction between dietary components or natural bioactive compounds and gut microbiota metabolites can regulate lipid metabolism. Additionally, natural products can shape the gut microbiota and improve barrier integrity by interacting with gut metabolites and their precursors, even in unfavourable conditions, potentially contributing to the alignment of host physiology.

Intermittent fasting promotes adipocyte mitochondrial fusion through Sirt3-mediated deacetylation of Mdh2.

Fat deposition and lipid metabolism are closely related to the morphology, structure and function of mitochondria. The morphology of mitochondria between fusion and fission processes is mainly regulated by protein posttranslational modification. Intermittent fasting (IF) promotes high expression of Sirtuin 3 (Sirt3) and induces mitochondrial fusion in high-fat diet (HFD)-fed mice. However, the mechanism by which Sirt3 participates in mitochondrial protein acetylation during IF to regulate mitochondrial fusion and fission dynamics remains unclear. This article demonstrates that IF promotes mitochondrial fusion and improves mitochondrial function in HFD mouse inguinal white adipose tissue. Proteomic sequencing revealed that IF increased protein deacetylation levels in HFD mice and significantly increased Sirt3 mRNA and protein expression. After transfecting with Sirt3 overexpression or interference vectors into adipocytes, we found that Sirt3 promoted adipocyte mitochondrial fusion and improved mitochondrial function. Furthermore, Sirt3 regulates the JNK-FIS1 pathway by deacetylating malate dehydrogenase 2 (MDH2) to promote mitochondrial fusion. In summary, our study indicates that IF promotes mitochondrial fusion and improves mitochondrial function by upregulating the high expression of Sirt3 in HFD mice, promoting deacetylation of MDH2 and inhibiting the JNK-FIS1 pathway. This research provides theoretical support for studies related to energy limitation and animal lipid metabolism.

Melatonin supplementation promotes muscle fiber hypertrophy and regulates lipid metabolism of skeletal muscle in weaned piglets.

Melatonin has been reported to play crucial roles in regulating meat quality, improving reproductive properties, and maintaining intestinal health in animal production, but whether it regulates skeletal muscle development in weaned piglet is rarely studied. This study was conducted to investigate the effects of melatonin on growth performance, skeletal muscle development, and lipid metabolism in animals by intragastric administration of melatonin solution. Twelve 28-d-old DLY (Duroc × Landrace × Yorkshire) weaned piglets with similar body weight were randomly divided into two groups: control group and melatonin group. The results showed that melatonin supplementation for 23 d had no effect on growth performance, but significantly reduced serum glucose content (P < 0.05). Remarkably, melatonin increased longissimus dorsi muscle (LDM) weight, eye muscle area and decreased the liver weight in weaned piglets (P < 0.05). In addition, the cross-sectional area of muscle fibers was increased (P < 0.05), while triglyceride levels were decreased in LDM and psoas major muscle by melatonin treatment (P < 0.05). Transcriptome sequencing showed melatonin induced the expression of genes related to skeletal muscle hypertrophy and fatty acid oxidation. Enrichment analysis indicated that melatonin regulated cholesterol metabolism, protein digestion and absorption, and mitophagy signaling pathways in muscle. Gene set enrichment analysis also confirmed the effects of melatonin on skeletal muscle development and mitochondrial structure and function. Moreover, quantitative real-time polymerase chain reaction analysis revealed that melatonin supplementation elevated the gene expression of cell differentiation and muscle fiber development, including paired box 7 (PAX7), myogenin (MYOG), myosin heavy chain (MYHC) IIA and MYHC IIB (P < 0.05), which was accompanied by increased insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 5 (IGFBP5) expression in LDM (P < 0.05). Additionally, melatonin regulated lipid metabolism and activated mitochondrial function in muscle by increasing the mRNA abundance of cytochrome c oxidase subunit 6A (COX6A), COX5B, and carnitine palmitoyltransferase 2 (CPT2) and decreasing the mRNA expression of peroxisome proliferator-activated receptor gamma (PPARG), acetyl-CoA carboxylase (ACC) and fatty acid-binding protein 4 (FABP4) (P < 0.05). Together, our results suggest that melatonin could promote skeletal muscle growth and muscle fiber hypertrophy, improve mitochondrial function and decrease fat deposition in muscle.

Integrative network analysis revealed the molecular function of folic acid on immunological enhancement in a sheep model.

We previously observed the beneficial role of folic acid supplemented from maternal or offspring diet on lamb growth performance and immunity. Twenty-four Hu lambs from four groups (mother received folic acid or not, offspring received folic acid or not) were used in the current study, which was conducted consecutively to elucidate the molecular regulatory mechanisms of folic acid in lambs by analyzing blood metabolome, liver transcriptome, and muscle transcriptome. Serum metabolomics analysis showed that L-homocitrulline, hyodeoxycholic acid, 9-Hpode, palmitaldehyde, N-oleoyl glycine, hexadecanedioic acid, xylose, 1,7-dimethylxanthine, nicotinamide, acetyl-N-formyl-5-methoxykynurenamine, N6-succinyl adenosine, 11-cis-retinol, 18-hydroxycorticosterone, and 2-acetylfuran were down-regulated and methylisobutyrate was up-regulated by the feeding of folic acid from maternal and/or offspring diets. Meanwhile, folic acid increased the abundances of S100A12 and IRF6 but decreased TMEM25 in the liver. In the muscle, RBBP9, CALCR, PPP1R3D, UCP3, FBXL4, CMBL, and MTFR2 were up-regulated, CYP26B1 and MYH9 were down-regulated by the feeding of folic acid. The pathways of bile secretion, biosynthesis of unsaturated fatty acids, linoleic acid metabolism, and herpes simplex virus 1 infection were changed by folic acid in blood, liver, or muscle. Further integrated analysis revealed potential interactions among the liver, blood, and muscle, and the circulating metabolites, hub gene, and pathways, which might be the predominant acting targets of folic acid in animals. These findings provide fundamental information on the beneficial function of folic acid no matter from maternal or offspring, in regulating animal lipid metabolism and immune enhancement, providing a theoretical basis for the use of folic acid from the view of animal health care.

Therapeutic effects of isosteviol sodium on non-alcoholic fatty liver disease by regulating autophagy via Sirt1/AMPK pathway

Isosteviol sodium (STVNa) is a beyerane diterpene synthesized via acid hydrolysis of stevioside, which can improve glucose and lipid metabolism in animals with diabetes. However, it remains unknown whether STVNa can exhibit a therapeutic effect on nonalcoholic fatty liver disease (NAFLD) and its underlying mechanism. We hypothesize that autophagic initiation may play a key role in mediating the development of NAFLD. Herein, we assessed the effects of STVNa on NAFLD and its underlying mechanisms. The results demonstrated that STVNa treatment effectively ameliorated NAFLD in rats fed high-fat diet (HFD). Moreover, STVNa decreased the expression of inflammation-related genes and maintained a balance of pro-inflammatory cytokines in NAFLD rats. STVNa also reduced lipid accumulation in free fatty acid (FFA)-exposed LO2 cells. In addition, STVNa attenuated hepatic oxidative stress and fibrosis in NAFLD rats. Furthermore, STVNa enhanced autophagy and activated Sirtuin 1/adenosine monophosphate-activated protein kinase (Sirt1/AMPK) pathway both in vivo and in vitro, thus attenuating intracellular lipid accumulation. In summary, STVNa could improve lipid metabolism in NAFLD by initiating autophagy via Sirt1/AMPK pathway. Therefore, STVNa may be an alternative therapeutic agent for treatment of NAFLD.

Transcriptome analysis of CRISPR/Cas9-mediated GPAM−/− in bovine mammary epithelial cell-line unravelled the effects of GPAM gene on lipid metabolism

Glycerol-3-phosphate acyltransferase mitochondrial (GPAM) is an enzyme in animal lipid metabolism pathways that catalyzes the initial and most committed step of glycerolipid biosynthesis. The present study mainly focused on exploring the relationship between the GPAM gene and the lipid metabolism of mammary epithelial cells and the effect of GPAM on the related pathways of lipid metabolism. The GPAM gene was knocked out entirely in bovine mammary epithelial cells(BMECs) using CRISPR/Cas9 technology, and the mechanism by which the GPAM gene regulates lipid metabolism in BMECs was confirmed. Furthermore, after the complete loss of GPAM, BMECs' triglycerides (TGs) and cholesterol (CHOL) levels were significantly decreased (p < 0.05). Concurrently, the content of octanoic acid, a medium-chain saturated fatty acid, increased substantially in BMECs. RNA-seq of GPAM−/− BMECs revealed that GPAM could affect the expression of genes related to lipid metabolism, downregulated the expression of Acyl-CoA synthetase long-chain family member 5 (ACSL5), Fatty Acid Binding Protein 3 (FABP3), Hormone-sensitive lipase (HSL), Protease, serine-2 (PRSS2), 1-Acylglycerol-3-Phosphate O Acyltransferase 4 (AGPAT4), and regulated the milk synthesis metabolism pathway.The findings revealed that a number of genes were expressed, a number of genes were differentially expressed genes (DEGs), and a number of GO terms were enriched, with a number of GO terms considerably increased. Further, the differentially expressed genes (DEGs) were significantly enriched in Fat digestion and absorption pathway, Fatty acid metabolic pathway, Biosynthesis of unsaturated fatty acids, Biosynthesis of unsaturated fatty acids and steroids, NF-kappa B signalling pathway, MAPK signalling pathway. In conclusion, the current research results show that GPAM is a crucial regulator of BMEC lipid metabolism. GPAM−/− BMEC may also become useful genetic materials and tools for future research on gene functions related to lipid and fatty acid metabolism. This study will contribute to the discovery of gene regulation and molecular mechanisms in milk fat synthesis.

The modified mitochondrial outer membrane carrier MTCH2 links mitochondrial fusion to lipogenesis.

Mitochondrial function is integrated with cellular status through the regulation of opposing mitochondrial fusion and division events. Here we uncover a link between mitochondrial dynamics and lipid metabolism by examining the cellular role of mitochondrial carrier homologue 2 (MTCH2). MTCH2 is a modified outer mitochondrial membrane carrier protein implicated in intrinsic cell death and in the in vivo regulation of fatty acid metabolism. Our data indicate that MTCH2 is a selective effector of starvation-induced mitochondrial hyperfusion, a cytoprotective response to nutrient deprivation. We find that MTCH2 stimulates mitochondrial fusion in a manner dependent on the bioactive lipogenesis intermediate lysophosphatidic acid. We propose that MTCH2 monitors flux through the lipogenesis pathway and transmits this information to the mitochondrial fusion machinery to promote mitochondrial elongation, enhanced energy production, and cellular survival under homeostatic and starvation conditions. These findings will help resolve the roles of MTCH2 and mitochondria in tissue-specific lipid metabolism in animals.

Effects of Low- and High-Level Gossypol and Sodium Butyrate Supplementation Under High-Level Gossypol Condition on Growth Performance and Intestinal Health of Hybrid Grouper (Epinephelus fuscoguttatus♀×Epinephelus lanceolatus♂)

The supplementation of gossypol in excess is noted to cause detrimental effects such as the reduction of antioxidant enzymes and disruption of lipid metabolism in animals. Studies regarding the effects of different levels of gossypol are very rare; thus, this study was conducted to evaluate the effects of low and high dietary levels of gossypol and of supplementation with 0.13 % sodium butyrate (NaB) under high gossypol conditions on the growth performance and intestinal health of hybrid grouper (Epinephelus fuscoguttatus♀×Epinephelus lanceolatus♂). Four treatments were used: Feed containing 40% fish meal was used as the control group [fishmeal (FM)], the FM diet plus 0.03% gossypol acetic acid (abbreviated as gossypol) as the low-level gossypol group (gL), FM + 0.15% gossypol was used as the high-level gossypol group (gH), and FM+0.15 % gossypol with 0.13 % NaB as the repair group (gHNaB). All diets were isonitrogenous and isolipidic. The results showed that the gL treatment significantly increased specific growth rate (SGR) and feed utilization; upregulated mRNA levels of distal intestinal transforming growth factor-β1 (tgfβ1), jam, occludin, claudin3, and zo1; and downregulated mRNA levels of il8, ifnγ, and akt. The gH treatment significantly reduced SGR and feed utilization; increased distal intestinal total nitric oxide synthase (NOS) activity and nitric oxide (NO) content; upregulated mRNA levels of distal intestinal tnfα, il1β, il6, ifnγ, caspase2, caspase9, and akt; and downregulated mRNA levels of tgfβ1, jam, and zo1. NaB supplementation significantly increased distal intestinal total NOS activity and NO content; downregulated distal intestinal tnfα, il1β, ifnγ, pi3k p85, and akt mRNA levels; and increased distal intestinal tgfβ1, jam, occludin, and zo1 mRNA levels. Above all, low- and high-level gossypol exhibited positive and negative effects on growth performance, distal intestinal anti-inflammatory capacity, and tight junctions, respectively, in hybrid groupers. NaB supplementation improved distal intestinal anti-inflammatory capacity and tight junctions in hybrid groupers to a certain extent.

Controlled lipid β-oxidation and carnitine biosynthesis by a vitamin D metabolite

Lactone-vitamin D3 is a major metabolite of vitamin D3, a lipophilic vitamin biosynthesized in numerous life forms by sunlight exposure. Although lactone-vitamin D3 was discovered 40 years ago, its biological role remains largely unknown. Chemical biological analysis of its photoaffinity probe identified the hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha (HADHA), a mitochondrial enzyme that catalyzes β-oxidation of long-chain fatty acids, as its selective binding protein. Intriguingly, the interaction of lactone-vitamin D3 with HADHA does not affect the HADHA enzymatic activity but instead limits biosynthesis of carnitine, an endogenous metabolite required for the transport of fatty acids into the mitochondria for β-oxidation. Lactone-vitamin D3 dissociates the protein-protein interaction of HADHA with trimethyllysine dioxygenase (TMLD), thereby impairing the TMLD enzyme activity essential in carnitine biosynthesis. These findings suggest a heretofore undescribed role of lactone-vitamin D3 in lipid β-oxidation and carnitine biosynthesis, and possibly in sunlight-dependent shifts of lipid metabolism in animals.

The effect of CPT1B gene on lipid metabolism and its polymorphism analysis in Chinese Simmental cattle

Carnitine palmitoyltransferase 1B (CPT1B) is a candidate gene that regulates livestock animal lipid metabolism and encodes the rate-limiting enzyme in fatty acid β-oxidation. To explore the effect of this gene on lipid metabolism in cattle, this study examined CPT1B gene polymorphism in Chinese Simmental cattle and the effect of CPT1B on lipid metabolism. The results showed that the triglyceride content increased significantly with increasing CPT1B gene expression in bovine fetal fibroblasts (BFFs) (p < 0.05), while CPT1B knockout led to decreased CPT1B expression and a downward trend in triglyceride levels. Correlation analysis showed a significant association between the g.119896238 G > C locus and Chinese Simmental cattle backfat thickness (p < 0.05). Backfat thickness was significantly greater in individuals with the GC genotype (0.93 ± 0.67 cm) than in those with the CC genotype (0.84 ± 0.60 cm). The g.119889302 T > C locus was significantly correlated with arachidonic acid content in Chinese Simmental cattle (p < 0.05). The arachidonic acid content in the longissimus muscle was significantly higher in CC genotype beef cattle (0.054 g/100 g) than in those with the other two genotypes (0.046 g/100 g, 0.049 g/100 g). These molecular markers can be effectively used for marker-assisted selection in cattle breeding.

Metabolic profiling of fatty acids in Tripterygium wilfordii multiglucoside- and triptolide-induced liver-injured rats.

Tripterygium wilfordii multiglucoside (TWM) is a fat-soluble extract from a Chinese herb T. wilfordii, that’s used in treating rheumatoid arthritis, nephrotic syndrome and other skin diseases. Triptolide (TP) is a major active component in TWM. However, clinical applications of TWM are limited by its various toxicities especially hepatotoxicity. In recent studies, it has been reported that drug-induced liver injury (DILI) could induce the disorder of lipid metabolism in animals. Hence, this study focuses on the metabolic profile of fatty acids in TWM- and TP-induced liver-injured rats. In serum and liver tissue, 16 free and 16 esterified fatty acids were measured by gas chromatography coupled with mass spectrometry. Metabolic profile of serum fatty acids in rats with liver injury was identified by multivariate statistical analysis. The fatty acid levels in the serum of TWM- and TP-treated rats significantly decreased, whereas those in the liver tissue of TWM- and TP-treated rats obviously increased when compared with the vehicle-treated rats. Four free fatty acids were identified as candidate biomarkers of TWM- and TP-induced liver injury. Therefore, the targeted metabolomic method may be used as a complementary approach for DILI diagnosis in clinic.

Effect of melatonin on visceral fat deposition, lipid metabolism and hepatic lipo-metabolic gene expression in male rats.

Melatonin (MT) influences lipid metabolism in animals; however, the mechanistic effect of melatonin on liver fat and abdominal adipose deposition requires further clarity. In order to study the effects of melatonin on lipid metabolism, and hepatic fat and abdominal adipose deposition in animals, twenty Sprague-Dawley (SD) rats of 6weeks of age with similar bodyweight were randomly divided into two groups: control (CTL) and MT-treated (10mg/kg/day). During a 60-day experiment, food intake and bodyweight were measured daily and weekly respectively. At the end of treatment, blood samples were collected to collect plasma to quantify hormones and metabolic indicators of lipid metabolism. In addition, organ and abdominal adipose depots including liver, and omental, perirenal, and epididymal fat were weighed. Liver tissue was sampled for sectioning, long-chain fatty acid (LCFA) quantification, and gene chip and Real-time quantitative PCR (qPCR) analyses. The results showed that liver weight and index (ratio of liver weight to body weight) in MT group reduced by 20.69% and 9.63% respectively; omentum weight and index reduced by 59.88% and 54.93% respectively, and epididymal fat weight reduced by 45.34% (p=0.049), relative to CTL. Plasma lipid indices, triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and total cholesterol (TC) with MT treatment decreased significantly compared with the control. Fat and 8 LCFA content in liver in MT group also decreased. Gene chip and qPCR demonstrated that there were 289 genes up-regulated and 293 genes down-regulated by MT. Further analysis found that the mRNA expression of lipolysis-related genes increased, while the mRNA expression of lipogenesis-related enzymes decreased (p<0.05) with MT. This study concluded that melatonin greatly affected fat deposition, and hepatic LCFA supply and the expression of genes associated with lipogenesis and lipolysis.

Integrated Metabolomics and Lipidomics Analysis Reveal Remodeling of Lipid Metabolism and Amino Acid Metabolism in Glucagon Receptor-Deficient Zebrafish.

The glucagon receptor (GCGR) is activated by glucagon and is essential for glucose, amino acid, and lipid metabolism of animals. GCGR blockade has been demonstrated to induce hypoglycemia, hyperaminoacidemia, hyperglucagonemia, decreased adiposity, hepatosteatosis, and pancreatic α cells hyperplasia in organisms. However, the mechanism of how GCGR regulates these physiological functions is not yet very clear. In our previous study, we revealed that GCGR regulated metabolic network at transcriptional level by RNA-seq using GCGR mutant zebrafish (gcgr−/−). Here, we further performed whole-organism metabolomics and lipidomics profiling on wild-type and gcgr−/− zebrafish to study the changes of metabolites. We found 107 significantly different metabolites from metabolomics analysis and 87 significantly different lipids from lipidomics analysis. Chemical substance classification and pathway analysis integrated with transcriptomics data both revealed that amino acid metabolism and lipid metabolism were remodeled in gcgr-deficient zebrafish. Similar to other studies, our study showed that gcgr−/− zebrafish exhibited decreased ureagenesis and impaired cholesterol metabolism. More interestingly, we found that the glycerophospholipid metabolism was disrupted, the arachidonic acid metabolism was up-regulated, and the tryptophan metabolism pathway was down-regulated in gcgr−/− zebrafish. Based on the omics data, we further validated our findings by revealing that gcgr−/− zebrafish exhibited dampened melatonin diel rhythmicity and increased locomotor activity. These global omics data provide us a better understanding about the role of GCGR in regulating metabolic network and new insight into GCGR physiological functions.