Expression Of Lipid Metabolism Genes Research Articles

Altering the ratio of palmitic, stearic, and oleic acids in dietary fat affects nutrient digestibility, plasma metabolites, growth performance, carcass, meat quality, and lipid metabolism gene expression of Angus bulls

This study evaluated the effects of changing the ratio of palmitic, stearic, and oleic acids in dietary fat on nutritional metabolism, growth performance, and meat quality of finishing Angus bulls. Bulls received the following three treatments: (1) a control diet without fat supplement (CON), (2) CON + mixed fatty acid supplement (58% C16:0 + 28% cis-9 C18:1; MIX), (3) CON + saturated fatty acid supplement (87% C16:0 + 10% C18:0; SFA). In summary, both fat treatment diets simultaneously increased saturated fatty acids C16:0 (P = 0.025), C18:0 (P < 0.001) and total monounsaturated fatty acids (P = 0.008) in muscle, thus balancing the ratio of unsaturated to saturated fatty acids in muscle. MIX diet increased the digestibility of dry matter (P = 0.014), crude protein (P = 0.038), and ether extract (P = 0.036). SFA diet increased the daily gain (P = 0.032) and intramuscular fat content (P = 0.043). The high content of C16:0 and C18:0 in the SFA diet promoted weight gain and fat deposition of beef cattle by increasing feed intake, up-regulating the expression of lipid uptake genes and increasing deposition of total fatty acids, resulting in better growth performance and meat quality.

AdipoRon Effect on Expression of Lipid Metabolism Genes in Cultured Human Primary Macrophages

Atherosclerosis is characterized by excessive uptake of cholesterol-rich low-density lipoprotein (LDL) by vascular wall macrophages. The macrophages are transformed into foam cells, lipids accumulate in the intima of arteries, atherosclerotic plaques arise, and cardiovascular diseases develop. Adiponectin is an adipose tissue adipokine and possess anti-atherogenic and anti-inflammatory activities, which are mediated by adiponectin binding to its receptors AdipoR1 and AdipoR2. To exert its anti-atherogenic effect, adiponectin may regulate the reverse cholesterol transport and prevent foam cells formation. The small-molecule adiponectin receptor agonist AdipoRon was assumed to modulate expression of reverse cholesterol transport and inflammation genes in human macrophages. Several AdipoRon concentrations (0, 5, 10, and 20 μM) were tested for effect on expression of the lipid metabolism genes ABCA1, ABCG1, APOA1, NR1H3 (LXRα), NR1H2 (LXRβ), PPARG, and ACAT1 and the inflammation genes IL6, TNFA, and TLR4 in cultured human primary macrophages and the THP-1 macrophage cell line. Cell viability was measured using the MTS assay. ABCA1, ABCG1, APOA1, NR1H3, NR1H2, PPARG, ACAT1, IL6, TNFA, and TLR4 mRNA levels in human primary macrophages were assessed by real-time PCR. The PPARG and ABCA1 relative mRNA levels were found to increase in human primary macrophages treated with 5 or 10 μM AdipoRon for 24 h. A higher AdipoRon concentration (20 μM) was cytotoxic to macrophages, especially THP-1 cells. The effect of AdipoRon on human macrophages and potential adiponectin receptor agonists are of interest to study in view of the need to develop new approaches to atherosclerosis prevention and treatment.

First Insights on the Administration of Insect Oil (Black Soldier Fly Larvae) in the Diet of Juvenile Onychostoma macrolepis.

The use of insect products in aquatic feed is the focus of the aquaculture industry. Black soldier fly larvae oil (BSFLO) has been examined as a potential lipid source for diets for some fish species, but its utilization on Onychostoma macrolepis has not been explored. The influences of substituting fish oil (FO) with BSFLO in the diet on growth, biological indicators, approximate composition, serum biochemistry, antioxidant capacity and expression of lipid metabolism genes in juvenile O. macrolepis were investigated in an eight-week feeding experiment. Four experimental diets were prepared by replacing 0 (control), 25% (BSFLO-25), 50% (BSFLO-50) and 100% (BSFLO-100) FO with BSFLO, and then randomly assigned to twelve aquariums with ten fish (1.75 ± 0.05 g) in each aquarium. The findings showed that the growth indicators, body composition and serum biochemistry in the BSFLO-25 and BSFLO-50 groups had no statistical differences from those of the control group. The activities of superoxide dismutase (SOD) (91.22-94.96 U/mgprot) and the contents of malondialdehyde (MDA) (1.12-1.16 nmol/mgprot) in the liver appeared to be significantly the highest and the lowest in the BSFLO-25, BSFLO-50 and BSFLO-100 groups (p < 0.05). The adipocyte size and intraperitoneal fat index value of fish fed on the BSFLO-100 diet were significantly decreased compared to the control group (p < 0.05). The expression levels of lipid catabolism genes pparα, (peroxisome proliferators-activated receptor alpha) and cpt1a (carnitine palmitoyltransferase 1 isoform a) in the BSFLO-100 group were significantly higher than those of the control group (p < 0.05). The above results indicated that it was feasible to replace 25-50% dietary FO with BSFLO in juvenile O. macrolepis. Dietary BSFLO supplementation could enhance the antioxidant capacity of the liver and suppress intraperitoneal fat accumulation in O. macrolepis. The use of other insect oils in the diets of this species will be evaluated in future research.

Discovery of a novel, liver-targeted thyroid hormone receptor-β agonist, CS271011, in the treatment of lipid metabolism disorders.

Thyroid hormone receptor β (THR-β) plays a critical role in metabolism regulation and has become an attractive target for treating lipid metabolism disorders in recent years. Thus, in this study, we discovered CS271011, a novel THR-β agonist, and assessed the safety and efficiency of CS271011 compared to MGL-3196 in vitro and in vivo. We conducted luciferase reporter gene assays to assess the activation of THR-β and α in vitro. C57BL/6J mice were fed a high-fat diet for 12 weeks, CS271011 was administered by gavage at the dose of 1 mg/kg and 3 mg/kg, and MGL-3196 was administered at the dose of 3 mg/kg for 10 weeks. Body weight, food intake, serum and hepatic parameters, histological analysis, pharmacokinetic studies, RNA sequencing of the liver and heart, and expression of hepatic lipid-metabolic genes were determined to evaluate the safety and efficiency of CS271011. Compared with MGL-3196, CS271011 showed higher THR-β activation in vitro. In the diet-induced obesity mice model, CS271011 demonstrated favourable pharmacokinetic properties in mice and was enriched in the liver. Finally, CS271011 improved dyslipidaemia and reduced liver steatosis in the diet-induced obesity murine model. Mechanistically, CS271011 and MGL-3196 showed potent regulation of lipid metabolism-related genes. CS271011 is a potent and liver-targeted THR-β agonist for treating lipid metabolism disorders.

Pomegranate Seed Oil as a Source of Conjugated Linolenic Acid (CLnA) Has No Effect on Atherosclerosis Development but Improves Lipid Profile and Affects the Expression of Lipid Metabolism Genes in apoE/LDLR-/- Mice.

The aim of this study was to evaluate the anti-atherosclerotic effect of pomegranate seed oil as a source of conjugated linolenic acid (CLnA) (cis-9,trans-11,cis-13; punicic acid) compared to linolenic acid (LnA) and conjugated linoleic acid (CLA) (cis-9,trans-11) in apoE/LDLR-/- mice. In the LONG experiment, 10-week old mice were fed for the 18 weeks. In the SHORT experiment, 18-week old mice were fed for the 10 weeks. Diets were supplied with seed oils equivalent to an amount of 0.5% of studied fatty acids. In the SHORT experiment, plasma TCh and LDL+VLDL cholesterol levels were significantly decreased in animals fed CLnA and CLA compared to the Control. The expression of PPARα in liver was four-fold increased in CLnA group in the SHORT experiment, and as a consequence the expression of its target gene ACO was three-fold increased, whereas the liver's expression of SREBP-1 and FAS were decreased in CLnA mice only in the LONG experiment. Punicic acid and CLA isomers were determined in the adipose tissue and liver in animals receiving pomegranate seed oil. In both experiments, there were no effects on the area of atherosclerotic plaque in aortic roots. However, in the SHORT experiment, the area of atherosclerosis in the entire aorta in the CLA group compared to CLnA and LnA was significantly decreased. In conclusion, CLnA improved the lipid profile and affected the lipid metabolism gene expression, but did not have the impact on the development of atherosclerotic plaque in apoE/LDLR-/- mice.

BETi enhance ATGL expression and its lipase activity to exert their antitumoral effects in triple-negative breast cancer (TNBC) cells

BackgroundTriple-Negative Breast Cancer (TNBC) is a subtype of breast cancer that differs from other types of breast cancers in the faster spread and worse outcome. TNBC presented limited treatment options. BET (Bromodomain and extra-terminal domain) proteins are epigenetic readers that control the expression of different oncogenic proteins, and their inhibition (BETi) is considered a promising anti-cancer strategy. Recent evidence demonstrated the involvement of BET proteins in regulation of metabolic processes.MethodsMDA-MB231 cells treated with JQ1 followed by RNA-sequencing analysis showed altered expression of lipid metabolic genes; among these, we focused on ATGL, a lipase required for efficient mobilization of triglyceride. Different in vitro approaches were performed to validate the RNA-sequencing data (qRT-PCR, immunofluorescence and flow cytometry). NMR (Nuclear Magnetic Resonance) was used to analyze the lipid reprogramming upon treatment. ATGL expression was determined by immunoblot and qRT-PCR, and the impact of ATGL function or protein knockdown, alone and in combination with BETi, was assessed by analyzing cell proliferation, mitochondrial function, and metabolic activity in TNBC and non-TNBC cells culture models.ResultsTNBC cells treated with two BETi markedly increased ATGL expression and lipolytic function and decreased intracellular lipid content in a dose and time-dependent manner. The intracellular composition of fatty acids (FAs) after BETi treatment reflected a significant reduction in neutral lipids. The short-chain FA propionate entered directly into the mitochondria mimicking ATGL activity. ATGL KD (knockdown) modulated the levels of SOD1 and CPT1a decreasing ROS and helped to downregulate the expression of mitochondrial ß-oxidation genes in favor of the upregulation of glycolytic markers. The enhanced glycolysis is reflected by the increased of the mitochondrial activity (MTT assay). Finally, we found that after BETi treatment, the FoxO1 protein is upregulated and binds to the PNPLA2 promoter leading to the induction of ATGL. However, FoxO1 only partially prompted the induction of ATGL expression by BETi.ConclusionsThe anti-proliferative effect achieved by BETi is helped by ATGL mediating lipolysis. This study showed that BETi altered the mitochondrial dynamics taking advantage of ATGL function to induce cell cycle arrest and cell death.Graphical Schematic representation of BETi mechanism of action on ATGL in TNBC cells. BETi induce theexpression of FoxO1 and ATGL, lowering the expression of G0G2, leading to a switch in metabolic status. Theinduced expression of ATGL leads to increased lipolysis and a decrease in lipid droplet content and bioavailabilityof neutral lipid. At the same time, the mitochondria are enriched with fatty acids. This cellular status inhibits cellproliferation and increases ROS production and mitochondrial stress. Interfering for ATGL expression, theoxidative phenotypic status mildly reverted to a glycolytic status where neutral lipids are stored into lipiddroplets with a consequent reduction of oxidative stress in the mitochondrial.

Alfalfa Xeno-miR168b Target CPT1A to Regulate Milk Fat Synthesis in Bovine Mammary Epithelial Cells.

It was shown that microRNAs (miRNAs) play an important role in the synthesis of milk fat; thus, this manuscript evaluated whether exogenous miRNA (xeno-miRNAs) from alfalfa could influence the milk fat content in dairy cows. At first, mtr-miR168b was screened from dairy cow milk and blood. Then, EdU staining, flow cytometry, Oil Red O staining, qRT-PCR, and WB were applied to explore the effect of xeno-miR168b on the proliferation, apoptosis, and lipid metabolism of bovine mammary epithelial cells (BMECs). Finally, in order to clarify the pathway that regulated the lipid metabolism of BMECs using xeno-miR168b, a double-luciferase reporter assay was used to verify the target gene related to milk fat. These results showed that overexpression of xeno-miR168b inhibited cell proliferation but promoted apoptosis, which also decreased the expression of several lipid metabolism genes, including PPARγ, SCD1, C/EBPβ, and SREBP1, significantly inhibited lipid droplet formation, and reduced triglyceride content in BMECs. Furthermore, the targeting relationship between CPT1A and xeno-miR168b was determined and it was confirmed that CPT1A silencing reduced the expression of lipid metabolism genes and inhibited fat accumulation in BMECs. These findings identified xeno-miR168b from alfalfa as a cross-kingdom regulatory element that could influence milk fat content in dairy cows by modulating CPT1A expression.

High-Fat Diet Promotes Adipogenesis in Offspring Female Rats Induced by Perinatal Exposure to 4-Nonylphenol.

Both high-fat diet (HFD) and 4-nonylphenol (4-NP) could affect fat formation in adipose tissue individually. We investigated whether HFD promote abnormal adipose tissue formation caused by early exposure to 4-NP in life and preliminarily explore the possible mechanisms involved. The first-generation rats were treated with HFD on postnatal day after pregnant rats exposure to 5 ug/kg/day 4-NP. Then, the second generation rats started to only receive normal diet without 4-NP or HFD. We analyzed organ coefficient and histopathology of fat tissues, biochemical index, and gene level involved in lipid metabolism in female offspring rats. HFD and 4-NP interaction synergistically increased birth weight, body weight, and organ coefficients of adipose tissue in offspring female rats. HFD accelerately aggravated abnormal lipid metabolism and increased the adipocyte mean areas around the uterus of the offspring female rats induced by prenatal exposure to 4-NP. HFD also facilitate the regulation of gene expression involved lipid metabolism in offspring female rats induced by perinatal exposure to 4-NP, even passed on to the second generation of female rats. Moreover, HFD and 4-NP interaction synergistically declined the gene and protein expression of estrogen receptor (ER) in the adipose tissue of second-generation female rats. HFD and 4-NP synergistically regulate the expression of lipid metabolism genes in adipose tissue of F2 female rats and promote adipose tissue generation, leading to obesity in offspring rats, which is closely related to low expression of ER. Therefore, ER genes and proteins may be involved in the synergistic effect of HFD and 4-NP.

Effects of dietary glycerol supplementation on meat quality, palatability, and lipid metabolism gene expression in the longissimus thoracis of Hanwoo steers

This study tested the hypothesis that dietary glycerol supplementation (GS) would affect growth of Hanwoo steers, beef marbling and palatability, and gene expression for lipid uptake and transport and lipogenesis in the longissimus thoracis (LT). Diets with or without 45.2 g daily glycerol supplementation/kg dry matter concentrate were tested in fourteen Hanwoo steers during a 16-week feeding trial. GS did not affect (P ≥ 0.40) the average daily gain or the gain-to-feed ratio. GS increased the LT marbling score (P = 0.01). GS enhanced (P ≤ 0.01) the sensory traits, including the flavor and overall acceptance of the LT. GS tended (0.05 < P ≤ 0.10) to upregulate mRNA levels of fatty acid translocase, lipoprotein lipase, and fatty acid binding protein 4 genes in the LT. These tendencies of upregulated expression of fatty acid uptake and cytosolic transport genes may, in part, contribute to the increased marbling by GS. The increased marbling degree caused by GS may improve palatability including the flavor and overall acceptance of the LT.

The ESCRT-III Protein Chmp1 Regulates Lipid Storage in the Drosophila Fat Body.

Defects in how excess nutrients are stored as triglycerides can result in several diseases including obesity, heart disease, and diabetes. Understanding the genes responsible for normal lipid homeostasis will help understand the pathogenesis of these diseases. RNAi screens performed in Drosophila cells identified genes involved in vesicle formation and protein sorting as important for the formation of lipid droplets; however, all of the vesicular trafficking proteins that regulate lipid storage are unknown. Here, we characterize the function of the Drosophila Charged multivesicular protein 1 (Chmp1) gene in regulating fat storage. Chmp1 is a member of the ESCRT-III complex that targets membrane localized signaling receptors to intralumenal vesicles in the multivesicular body of the endosome and then ultimately to the lysosome for degradation. When Chmp1 levels are decreased specifically in the fly fat body, triglyceride accumulates while fat-body-specific Chmp1 overexpression decreases triglycerides. Chmp1 controls triglyceride storage by regulating the number and size of fat body cells produced and not by altering food consumption or lipid metabolic enzyme gene expression. Together, these data uncover a novel function for Chmp1 in controlling lipid storage in Drosophila and supports the role of the endomembrane system in regulating metabolic homeostasis.

Nimbin analogs N5 and N7 regulate the expression of lipid metabolic genes and inhibit lipid accumulation in high-fat diet-induced zebrafish larvae: An antihyperlipidemic study

BackgroundExcess accumulation of lipids leads to obesity. Triterpenoids are a group of plant compounds which poses various biological activities. The biological activities of Nimbin analogs N5 and N7 were addressed in this study on inhibiting lipid aggregation and underlying the derivatives molecular mechanisms for a therapeutical approach. AimThis study aims to evaluate the anti-adipogenic activity of semi-natural Nimbin analogs, N5 and N7, on zebrafish larvae induced with oxidative stress due to a high-fat diet (HFD) and adipogenesis using specific fluorescent stains. Materials and methodsZebrafish at 4 days post fertilized (dpf) larvae were divided into groups for the HFD diet along with exposure to various concentrations of N5 and N7. HFD induced accumulation of neutral lipids and triglycerides (Oil Red O and Nile red staining, respectively) with weight gain, which generated intracellular ROS (DCFH-DA staining) and superoxide anion production (DHE staining) with depleted glutathione levels (NDA staining) were assayed. HFD exposure promoted the accumulation of inflammatory macrophages (Neutral red staining) and impaired glucose metabolism (2NBDG staining). The ability of N5 and N7 to reduce total regulating lipogenic specific genes C/EBP-α, SREBP-1 and FAS were evaluated using relative gene expression. Key findingsThe Nimbin analogues N5 and N7 suppressed adipogenesis, forming intracellular ROS and superoxide anion while simultaneously restoring glutathione levels. The analogues significantly lowered total TC and TG levels, prevented inflammatory macrophage build-up and boosted glucose absorption. Also, N5 and N7 down-regulate the lipogenic-specific genes. SignificanceNimbin analogs N5 and N7 enhance lipolysis and inhibit adipogenesis in in-vivo zebrafish larvae model.

Correlation analysis of lipid metabolism genes with the immune microenvironment in gastric cancer and the construction of a novel gene signature.

Lipid metabolism reprogramming plays an important role in cell growth, proliferation, angiogenesis and invasion of cancer. However, the prognostic value of lipid metabolism during gastric cancer (GC) progression and the relationship with the immune microenvironment are still unclear. The aim of this study was to clarify the correlation between lipid metabolism genes and GC immunity. We obtained 350 patients from The Cancer Genome Atlas (TCGA) and 355 patients from Gene Expression Omnibus (GEO) databases. Lipid metabolism-related gene datasets were obtained from the Reactome and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Molecular subtypes were obtained by Consensus clustering, and subtype immune status was analyzed using ESTIMATE, TIMER and microenvironmental cell population counter (MCP Counter) algorithm for immune analysis. Functional analyses included the application of Gene Set Enrichment Analysis (GSEA), KEGG, gene ontology (GO), and Protein-Protein Interaction Networks (PPI) to evaluate the molecular mechanisms of different subtypes. Weighted gene co-expression network analysis (WGCNA) was used to identify genes associated with immunity. The LASSO algorithm and multivariate Cox regression analysis were used to construct prognostic risk models. Based on the lipid metabolism genes found in GC, patients with GC can be divided into two subgroups with significantly different survival. The subgroup with a better prognosis presented higher immune scores and immune infiltrating cell abundance. 1170 immune-related genes were screened by WGCNA, and further screening by PPI network analysis revealed that PTPRC, CD4, ITGB2 and LCP2 were closely associated with immune cells. Combined with the TIDE score results, it was found that the population with high expression of the above genes might be more sensitive to immunotherapy. In addition, a survival prediction model for GC was developed based on five survival-related lipid metabolism genes, PIAS4, PLA2R1, PRKACA, SLCO1A2 and STARD4. The ROC analysis over time showed that the risk prediction score model had good stability. Lipid metabolism gene expression is correlated with the immune microenvironment in GC patients and can accurately predict their prognosis. Studies on lipid metabolism and GC immunity can help to screen the population for immunotherapy benefits.

Water extract from artichoke ameliorates high-fat diet-induced non-alcoholic fatty liver disease in rats

BackgroundThe “multiple-hit” hypothesis is currently the most widely accepted theory for non-alcoholic fatty liver disease (NAFLD) pathogenesis. The present study aimed to investigate the effects of the water extract of artichoke (WEA) on NAFLD and its underlying mechanism.MethodsRats were fed a high-fat diet (HFD) for 8 weeks to induce NAFLD and then treated with WEA at three doses (0.4, 0.8, and 1.6 g/kg body weight, BW) for 8 weeks. At the end of the intervention, serum biochemical parameters, hepatic antioxidant capacity, hepatic levels of pro-inflammatory cytokines, liver histopathology, hepatic inflammatory gene and lipid metabolism gene expression, and Akt and p-Akt (S473) protein levels were determined.ResultsThe body weight, liver weight, liver triglyceride (TG) and serum levels of TG, total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, glucose, and insulin were all significantly reduced in the WEA-treated groups (0.8 and 1.6 g/kg BW) compared with the HFD group (P < 0.01). A significant decrease in hepatic content of malondialdehyde (P < 0.01) and glutathione (P < 0.01), as well as a significant increase in liver superoxide dismutase activity (P < 0.01) were observed in WEA-treated groups (0.8 and 1.6 g/kg BW) compared to the HFD group. In addition, there was a marked decrease in the hepatic levels of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in the WEA-treated groups compared to the HFD group (P < 0.01). In line with these findings, the histopathology of the livers of rats treated with WEA (0.8 and 1.6 g/kg BW) showed a decrease in steatosis, ballooning, and lobular inflammation. Mechanistically, the reduced hepatic TG content might be related to the downregulation of lipogenic genes (SREBP1c, FASN, SCD1) and upregulation of lipolytic gene (PPARα), and the improved insulin signaling might be associated with the observed increase in antioxidant activity and reduction in inflammation in the WEA-treated groups.ConclusionThe hepatoprotective role of WEA in NAFLD may be attributed to its anti-steatotic, antioxidant, anti-inflammatory, and anti-insulin resistance effects.

Effects of dietary berberine on growth performance, lipid metabolism, antioxidant capacity and lipometabolism-related genes expression of AMPK signaling pathway in juvenile black carp (Mylopharyngodon piceus) fed high-fat diets.

This study aimed to investigate the effects of high-fat diet (HFD) supplemented with berberine on growth, lipid metabolism, antioxidant capacity and lipometabolism-related genes expression of AMPK signaling pathway in juvenile black carp (Mylopharyngodon piceus). Five hundred and forty healthy fish (4.04 ± 0.01g) were randomly distributed into six groups, and fed six experimental diets: normal-fat diet (NFD, 5% fat), HFD (15% fat), and four HFDs supplemented with graded levels of berberine, respectively. The results showed that, compared with fish fed NFD, HFD had no effects on the growth of fish except for reducing survival rate, whereas HFD caused extensive lipid accumulation, oxidative stress injury and hepatic abnormalities. However, compared with the HFD group, fish fed HFD containing an appropriate berberine (98.26 or 196.21mg/kg) improved the growth performance, increased hepatic lipid metabolism and antioxidant enzymes activities, and up-regulated the mRNA expression levels of ampk subunits and lipolysis genes such as pparα, cpt-1, acox, atgl and hsl (P < 0.05). Meanwhile, HFD supplemented with an appropriate berberine reduced crude lipid contents in liver and whole-body, decreased serum lipid contents, and ALT and AST activities, and down-regulated the mRNA expression levels of lipogenesis genes such as srebp-1, acc1, gpat, fas and pparγ, and lipid transporter genes such as fatp, fabp and fat/cd36 (P < 0.05). Thus, HFD supplemented with an appropriate berberine could improve growth of black carp, promote lipid metabolism and enhance antioxidant capacity. The lipid-lowering mechanism of berberine might be mediated by activating AMPK pathway, up-regulating lipolysis genes expression, and down-regulating lipogenesis and transport genes expression.

Naringenin inhibits lipid accumulation by activating the AMPK pathway in vivo and vitro

The aim of this study was to explore the lipid-lowering effect of naringenin and the underlying mechanism in high-fat-diet-fed SD rats and 3T3-L1 cells. In this study, SD rats were divided into the normal chow diet group (NCD), high fat diet group (HFD), three treatment groups feeding high-fat diet with naringenin (100, 200, 400 mg/kg) for 12 weeks. Results indicated that naringenin treatment decreased total cholesterol (TC), triglyceride (TG) and the non-high-density lipoprotein cholesterol (non-HDL-C) levels in serum. Naringenin also alleviated hepatic steatosis and reduced the adipocyte size in the epididymis in high-fat-diet-induced SD rats. In addition, naringenin (25−75 µg/mL) decrease TG and TC levels in 3T3 mature adipocytes. The molecular mechanism of naringenin in the treatment of obesity were predicted by using network pharmacology. Real-time PCR analysis results showed that naringenin regulated the expression of lipid metabolism genes. Meanwhile, naringenin increased the AMPK (AMP-activated protein kinase) activity and the expression of AMPK phosphorylated protein in 3T3 mature adipocytes. And the inhibitory effect of naringenin on lipid accumulation in 3T3 adipocytes was abolished by Compound C. Molecular docking results indicated that naringenin could bind to AMPK protein. These results indicated naringenin reduced lipid accumulation through AMPK pathway.

Induction mechanism of cigarette smoke components (CSCs) on dyslipidemia and hepatic steatosis in rats

ObjectiveThe purpose of this study was to explore the effect of cigarette smoke component (CSC) exposure on serum lipid levels in rats and the underlying molecular mechanism.MethodsMale SPF-grade SD rats were randomly divided into a control group and a CSC exposure group, with the CSC group being exposed to CSC for 6 weeks. RT–PCR and Western blotting methods were used to detect lipid metabolism gene expression in rats, and 16S RNA gene sequencing was used to detect the gut microbiota in the rat cecum. Rat serum exosomes were prepared and identified, and the interaction of exosomal miR-291a-3p and miR-126a-5p with AMPK and CYP7A1 was detected by a dual luciferase reporter gene assay (DLRG).ResultsSerum indicators, including cholesterol levels and trimethylamine oxide (TMAO) content, were significantly affected in the CSC exposure group compared with the control group (P < 0.05), and the expression levels of adenylate-activated protein kinase (AMPK), acetyl-coenzyme A carboxylase (ACC) and HMG-CoA reductase (HMG-CoAR) genes were significantly increased (P < 0.05) in the liver, while the expression level of cholesterol 7α-hydroxylase (CYP7A1) was markedly decreased (P < 0.01). 16S rRNA gene sequencing of the gut microbiota in the rat cecum showed that the abundance of Firmicutes in the CSC group increased significantly at the phylum level, while the abundances of Bacteroidota and Spirochaetota were reduced significantly (P < 0.01). The relative abundance of Romboutsia, Turicibacter, and Clostridium sensu stricto increased significantly (P < 0.01), and the relative abundance of Prevotella, Muribaculaceae_norank, Lachnospiraceae NK4A136 group, Roseburia, Treponema, and Ruminococcus significantly decreased (P < 0.01) at the genus level. In addition, the exosome miR-291a-3p and miR-126a-5p levels were markedly regulated by CSC exposure (P < 0.01). The interactions of miR-291a-3p and miR-126a-5p with AMPK and CYP7A1 mRNA were also validated by the DLRG method.ConclusionsIn summary, the rat dyslipidemia induced by CSC exposure may be related to the interference of gut microbiota structure and interaction of miRNAs from serum exosomes with target mRNAs, which further regulated AMPK-ACC/CYP7A1 signaling in rats.

Dietary supplementation with Tolypocladium sinense mycelium prevents dyslipidemia inflammation in high fat diet mice by modulation of gut microbiota in mice.

Obesity is a risk factor for many serious health problems, associated with inflammation, hyperlipidemia, and gut dysbiosis. Prevention of obesity is especially important for human health. Tolypocladium sinense is one of the fungi isolated from Chinese caterpillar fungus, which is a traditional Chinese medicine with putative gut microbiota modulation effects. Here, we established a high-fat diet (HFD)-induced hyperlipidemia mice model, which was supplemented with lyophilized T. sinense mycelium (TSP) daily to evaluate its anti-obesity effects. The results indicated that TSP supplementation can effectively alleviate the inflammatory response and oxidative stress levels caused by obesity. TSP significantly prevented obesity and suppressed dyslipidemia by regulating the expression of lipid metabolism genes in the liver. TSP is also effective in preventing the HFD-induced decline in short-chain fatty acid (SCFA) content. Gut microbiota profiling showed that TSP supplementation reversed HFD diet-induced bacterial abundance and also altered the metabolic pathways of functional microorganisms, as revealed by KEGG analysis. It is noteworthy that, correlation analysis reveals the up-regulated gut microbiota (Lactobacillus and Prevotella_9) are closely correlated with lipid metabolism parameters, gene expression of liver lipid metabolism and inflammatory. Additionally, the role of TSP in the regulation of lipid metabolism was reconfirmed by fecal microbiota transplantation. To sum up, our results provide the evidence that TSP may be used as prebiotic agents to prevent obesity by altering the gut microbiota, alleviating the inflammatory response and regulating gene expression of liver lipid metabolism.

Enantioselective toxic effects of the novel chiral antifungal agrochemical penthiopyrad in the early life stage of zebrafish (Danio rerio)

Penthiopyrad was extensively applied in agricultural production, however, the toxicities information of the penthiopyrad enantiomers on early life stages of aquatic organism were limited. This study investigated the enantioselective toxicity of penthiopyrad on the early life stage of zebrafish by acute toxicity, sublethal toxic effects and the mRNA relative expression levels of genes related to succinate dehydrogenase, cardiac development, and lipid metabolism. The results showed that the 96-h-LC50 of penthiopyrad racemate and enantiomers to zebrafish embryos were Rac-: 2.784 mg/L; R-(−)-: 3.528 mg/L; S-(+)-: 1.882 mg/L. Penthiopyrad exposure induced autonomous movement abnormalities, slowed heart rate and delayed hatching in zebrafish embryos, and caused developmental toxic effects such as pericardial edema and yolk sac edema. The mRNA relative expression levels results showed that penthiopyrad exposure induced significant enantioselectivity effect for the expression of the Sdha, Pr1 and Nkx2.5 with a 1.94–4.98-fold difference between different enantiomers, and significantly affected succinate dehydrogenase (energy metabolism), lipid metabolism and cardiac development-related genes expression. In general, S-(+)-penthiopyrad induced higher toxic effects in zebrafish embryos, and mitochondrial dysfunction may be an important cause of abnormal development. This study contributed to improve the comprehensive risk assessment and enantiomeric research system of penthiopyrad to early life stage of zebrafish.

Molecular Classification of Genes Associated with Hypoxic Lipid Metabolism in Pancreatic Cancer.

Abnormal lipid metabolism often occurs under hypoxic microenvironment, which is an important energy supplement for cancer cell proliferation and metastasis. We aimed to explore the lipid metabolism characteristics and gene expression features of pancreatic ductal adenocarcinoma (PDAC) related to hypoxia and identify biomarkers for molecular classification based on hypoxic lipid metabolism that are evaluable for PDAC prognosis and therapy. The multiple datasets were analyzed integratively, including corresponding clinical information of samples. PDAC possesses a distinct metabolic profile and oxygen level compared with normal pancreatic tissues, according to the bioinformatics methods. In addition, a study on untargeted metabolomics using Ultra Performance Liquid Chromatography Tandem Mass Spectrometry(UPLC-MS) revealed lipid metabolites differences affected by oxygen. Analysis of PDAC gene expression profiling in The Cancer Genome Atlas (TCGA) revealed that the sphingolipid process correlates closely with HIF1α. According to the characters of HIF-1 and sphingolipid, samples can be clustered into three subgroups using non-negative matrix factorization clustering. In cluster2, patients had an increased survival time. Relatively high MUC16 mutation arises in cluster2 and may positively influence the cancer survival rates. This study explored the expression pattern of lipid metabolism under hypoxia microenvironment in PDAC. On the basis of metabolic signatures, we identified the prognosis subtypes linking lipid metabolism to hypoxia. The classifications may be conducive to developing personalized treatment programs targeting metabolic profiles.

Effect of n-6/n-3 PUFA ratio on body fat deposition, tissues fatty acid composition and key genes expression of liver lipid metabolism in silver foxes (Vulpes vulpes fulva) during the winter fur-growth period.

The proportion of n-6/n-3 polyunsaturated fatty acid (PUFA) plays an important role in regulating lipid metabolism. This study aimed to investigate the effects of dietary n-6/n-3 PUFA ratios on body fat deposition, tissues fatty acid composition, and gene expression of liver lipid metabolism of silver foxes during the winter fur growth period. Forty-eight age-matched male silver foxes with similar body weights were randomly divided into four dietary groups for 47 days, which were fed n-6/n-3 PUFA ratio with 3, 18, 41, and 136 experimental diets, respectively. Dietary n-6/n-3 PUFA ratio did not significantly influence fat deposition parameters except for hepatic fat content. The variation trend of the fatty acid composition of liver, intramuscular fat, and subcutaneous fat in silver fox was directly related to dietary fatty acid content (p < 0.05). With the dietary n-6/n-3 PUFA ratio increasing, the expression of liver fatty acid synthase (FAS) mRNA and peroxisome proliferator-activated receptor (PPAR) mRNA exhibited the trend of first decreasing and then increasing (p < 0.05), whereas L-fatty acid binding protein (L-FABP) mRNA expression showed a gradual increasing trend (p < 0.05). In summary, silver foxes fed an n-6/n-3 PUFA ratio 18:1 diet (supplementing with 9.38% corn oil and 4.62% soybean oil) was more conducive to lipid decomposition, PUFA transport, and utilization of tissues, thereby meeting it for supplying energy and withstanding the cold.