Comparison of Lipid Composition between Quasipaa spinosa Oil and Rana catesbeiana Oil and Its Effect on Lipid Accumulation in Caenorhabditis elegans.

Frog oil has been recognized for its nutritional and medicinal value. However, there is limited research on the role of frog oil in preventing obesity. In this study, we aimed to investigate the lipid composition of Quasipaa spinosa oil (QSO) and Rana catesbeiana oil (RCO) using lipidomics analysis. We compared the lipid accumulation effects of these two kinds of frog oils and soybean oil (SO) in Caenorhabditis elegans (C. elegans). Additionally, we determined the gene expression related to lipid metabolism and used the nhr-49 mutant (RB1716) and sir-2.1 mutant (VC199) for validation experiments. The results showed that the lipid composition of QSO and RCO was significantly different (p < 0.05), and QSO was rich in more polyunsaturated fatty acids (PUFAs). After feeding C. elegans, the lipid accumulation of the QSO group was the lowest among the three dietary oil groups. In addition, compared with RCO and SO, QSO significantly inhibited the production of malondialdehyde (MDA) and increased the activity of superoxide dismutase (SOD). The effects of three kinds of dietary oils on the fatty acid composition of C. elegans were significantly different. Compared with SO and RCO, QSO significantly up-regulated (p < 0.05) the expression of sir-2.1 and ech-1 genes. The results showed that QSO might reduce lipid accumulation through the SIRT1 and nuclear hormone signaling pathways. Such a situation was verified experimentally by the nhr-49 mutant (RB1716) and sir-2.1 mutant (VC199). This study proposed a new functional oil, laying the groundwork for developing functional foods from Quasipaa spinosa.

Fucoxanthin extract ameliorates obesity associated with modulation of bile acid metabolism and gut microbiota in high-fat-diet fed mice.

PURPOSE: Fucoxanthin extract (FX) is a type of carotenoid with a beneficial effect against obesity. The purpose of this study was to explore its precise action mechanism of losing weight. METHODS: A high-fat diet induced obesity mouse model was established to study the effects of different doses of FX on C57BL/6J male mice for 12 weeks. Following intervention, serum indices, tissue sections, liver gene expression, and intestinal microorganisms were analyzed. RESULTS: FX at low, medium, and high dosages (80, 160, and 320 mg/kg/day, respectively) for 12 weeks was associated with the lower body weight of mice when compared to that of high-fat-diet fed mice. It also improved glucose tolerance as well as serum lipid levels, and reduced fat accumulation. Significant regulation of bile acid metabolism and intestinal microbiota may contribute to the above effects. The bile acids in the FXH group were significantly increased. A low-dose and a medium-dose FX increased the level of transmembrane G protein-coupled receptor 5 (TGR5); a low-dose and high-dose FX increased the farnesoid X receptor (FXR) expression, and a medium-dose had no effect. 16S rRNA sequencing indicated that the Lachnospiraceae and Oscillospiraceae contributed to the beneficial effects of FX. CONCLUSION: Our study sheds light on mechanisms behind the weight-lowering of FX, and manifested that bile acid metabolism and gut microbiota may be potential therapies. These results support that FX is a valuable candidate for promoting health and alleviating obesity.

Effects of oleoylethanolamide supplementation on the expression of lipid metabolism-related genes and serum NRG4 levels in patients with non-alcoholic fatty liver disease: A randomized controlled trial.

BACKGROUND: This study investigated the effects of oleoylethanolamide (OEA) supplementation on the expression levels of SIRT1, AMPK, PGC-1α, PPAR-γ, CEBP-α and CEBP-ß genes and serum neuregulin 4 (NRG4) levels in patients with non-alcoholic fatty liver diseases (NAFLD). METHODS: Sixty obese patients with NAFLD were equally allocated into either OEA or placebo group for 12 weeks. The mRNA expression levels of genes were determined using the reverse transcription polymerase chain reaction (RT-PCR) technique. Serum NRG4 level was also assessed using an enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: At the endpoint, mRNA expression levels of SIRT1(p = 0.001), PGC-1α (p = 0.011) and AMPK (p = 0.019) were significantly higher in the OEA group compared to placebo group. However, no significant differences were observed in the expression levels of PPAR-γ, CEBP-α and CEBP-ß between the two groups. Serum NRG4 levels significantly increased in the OEA group compared with the placebo group after controlling for confounders (p = 0.027). In the OEA group, significant relationships were found between percent of changes in the expression levels of the SIRT1, AMPK and PGC-1α as well as serum NRG4 level with percent of changes in some anthropometric measures. Moreover, in the intervention group, percent of changes in high-density lipoprotein cholesterol was positively correlated with percent of changes in the expression levels of the SIRT1 and AMPK. While, percent of changes in triglyceride was inversely correlated with percent of changes in the expression levels of SIRT1. CONCLUSION: OEA could beneficially affect expression levels of some lipid metabolism-related genes and serum NRG4 level. "REGISTERED UNDER IRANIAN REGISTRY OF CLINICAL TRIALS IDENTIFIER NO: IRCT20090609002017N32".

In vitro maturation in synthetic oviductal fluid increases gene expression associated with quality and lipid metabolism in bovine oocytes.

Traditionally, in vitro oocyte and embryo culture progresses through a series of varying culture medium. To investigate simplifying the in vitro production of bovine cumulus-oocyte complexes (COCs), this study used synthetic oviductal fluid (SOF) supplemented with conjugated linoleic acid (CLA). Special interest was placed on gene expression linked to lipid metabolism and oocyte maturation. COCs were matured in different media: Medium 199 (M199 group), M199 with 100 µM CLA (M199 + CLA group), SOF (SOF group), and SOF with 100 µM CLA (SOF + CLA group). COCs matured with SOF showed a higher relative abundance of mRNA of quality indicators gremlin 1 (GREM1) and prostaglandin-endoperoxide synthase 2 (PTGS2) in oocytes, and GREM1 in cumulus cells compared with in the M199 group. SOF medium COCs had a higher relative abundance of fatty acid desaturase 2 (FADS2) compared with the M199 group, which is essential for lipid metabolism in oocytes. Furthermore, the abundance of stearoyl-coenzyme A desaturase 1 (SCD1) in oocytes matured with SOF was not influenced by the addition of CLA, whereas the relative abundance of SCD1 was reduced in M199 medium with CLA. We concluded that maturation in SOF medium results in a greater abundance of genes linked to quality and lipidic metabolism in oocytes, regardless of the addition of CLA.

[Electroacupuncture intervention improves lipid metabolism and promotes browning of white adipose tissue by activating AMPK/Sirt1 pathway and up-regulating Nrg4 content in middle-aged and aged obese rats].

OBJECTIVE: To investigate the mechanism of electroacupuncture （EA） in promoting the browning of white adipose tissue in middle-aged and aged obese rats induced by high fat by regulating AMP-activated protein kinase （AMPK） /silence-information regulatory factor 1 （Sirt1） pathway and neuregulin 4 （Nrg4）. METHODS: Twenty-four male SD rats were randomized into blank control, model and EA groups （n=8 per group）. The obesity model was established by feeding the rats with high-fat diet for 6 weeks. For the EA group, EA （2 Hz/15 Hz, 1.5 mA） was applied to "Guanyuan" （CV4） and bilateral "Shenshu" （BL23）, "Fenglong" （ST40） and "Tianshu" （ST25） for 20 min, once a day, 5 days a week for 6 weeks. Rats of the blank control and model groups were also restrained for 20 min. The body mass and food intake were measured every week, and the Lee's index, epididymal fat, perirenal fat and brown adipose tissue were weighed. The contents of serum total cholesterol （TC）, triglyceride （TG）, high density lipoprotein cholesterol （HDL-C）, low density lipoprotein cholesterol （LDL-C） and norepinephrine （NE） were determined by ELISA. H.E. staining was used to observe the morphological changes of white and brown adipose tissue. The mRNA expression levels of mitochondrial uncoupling protein 1 （UCP1）, peroxisome proliferator activated receptor γ co-activator 1α （PGC-1α）, PR-domain protein 16 （PRDM16）, peroxisome proliferator activated receptor γ （PPARγ） and Nrg4 in the adipose tissue were detected by quantitative real time PCR, and the protein expression levels of Nrg4, AMPKα, Sirt1 and interleukin-6 （IL-6） in the white and brown adipose tissue were detected by Western blot. RESULTS: Compared with the blank control group, the body mass, food intake, the Lee's index, epididymal fat and perirenal fat mass, and serum TG, TC and LDL-C contents and the expression level of IL-6 protein were significantly increased （P<0.01, P<0.05, P<0.001）, and the brown adipose mass, serum HDL-C and NE contents, the expression levels of UCP1, PGC-1α, PRDM16, PPARγ and Nrg4 mRNAs, and the protein expression levels of AMPKα, Sirt1 and Nrg4 proteins in both white and brown adipose tissues were significantly decreased in the model group （P<0.01, P<0.05）. After EA intervention, the increased levels of body mass, food intake, Lee's index, epididymal fat and perirenal fat mass, serum TG, TC and LDL-C contents, and the expression of IL-6 protein, and the decreased levels of brown adipose mass, serum HDL-C and NE contents, expression levels of UCP1, PGC-1α, PRDM16, PPARγ and Nrg4 mRNAs, and those of AMPKα, Sirt1 and Nrg4 proteins in both white and brown adipose tissues were apparently reversed（P<0.05, P<0.01, P<0.001）. H.E. staining showed an increase of the volume and content of intracellular vacuoles of both white and brown adipose tissues, disordered arrangement of cells with vague boundary in the model group, which was relatively milder including a decrease of volume and content of vacuoles of both white and brown adipose, neat arrangement of cells with clear boundary. CONCLUSION: EA intervention can improve lipid metabolism and promote white adipose tissue browning in middle-aged and aged obese rats, which is possibly associated with its functions in activating AMPK/Sirt1 signaling pathway and up-regulating the level of Nrg4.

Berberine Reduces Lipid Accumulation in Obesity via Mediating Transcriptional Function of PPARδ.

Obesity is defined as a dampness-heat syndrome in traditional Chinese medicine. Coptidis Rhizoma is an herb used to clear heat and eliminate dampness in obesity and its complications. Berberine (BBR), the main active compound in Coptidis Rhizoma, shows anti-obesity effects. Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor proteins that regulate the expression of genes involved in energy metabolism, lipid metabolism, inflammation, and adipogenesis. However, whether PPARs are involved in the anti-obesity effect of BBR remains unclear. As such, the aim of this study was to elucidate the role of PPARs in BBR treatment on obesity and the underlying molecular mechanisms. Our data showed that BBR produced a dose-dependent regulation of the levels of PPARγ and PPARδ but not PPARα. The results of gene silencing and specific antagonist treatment demonstrated that PPARδ is key to the effect of BBR. In 3T3L1 preadipocytes, BBR reduced lipid accumulation; in high-fat-diet (HFD)-induced obese mice, BBR reduced weight gain and white adipose tissue mass and corrected the disturbed biochemical parameters, including lipid levels and inflammatory and oxidative markers. Both the in vitro and in vivo efficacies of BBR were reversed by the presence of a specific antagonist of PPARδ. The results of a mechanistic study revealed that BBR could activate PPARδ in both 3T3L1 cells and HFD mice, as evidenced by the significant upregulation of PPARδ endogenous downstream genes. After activating by BBR, the transcriptional functions of PPARδ were invoked, exhibiting negative regulation of CCAAT/enhancer-binding protein α (Cebpα) and Pparγ promoters and positive mediation of heme oxygenase-1 (Ho-1) promoter. In summary, this is the first report of a novel anti-obesity mechanism of BBR, which was achieved through the PPARδ-dependent reduction in lipid accumulation.

Integrated Analysis of lncRNA-mRNA Regulatory Networks Related to Lipid Metabolism in High-Oleic-Acid Rapeseed.

A high oleic acid content is considered an essential characteristic in the breeding of high-quality rapeseed in China. Long-chain non-coding RNA (lncRNA) molecules play an important role in the plant's growth and its response to stress. To better understand the role of lncRNAs in regulating plant reproductive development, we analyzed whole-transcriptome and physiological data to characterize the dynamic changes in lncRNA expression during the four representative times of seed development of high- and low-oleic-acid rapeseed in three regions. We identified 21 and 14 lncRNA and mRNA modules, respectively. These modules were divided into three types related to region, development stages, and material. Next, we analyzed the key modules related to the oil content and the oleic acid, linoleic acid, and linolenic acid contents with physiological data and constructed the key functional network analysis on this basis. Genes related to lipid metabolism, such as 3-ketoacyl-CoA synthase 16 (KCS16) and acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), were present in the co-expression network, suggesting that the effect of these genes on lipid metabolism might be embodied by the expression of these lncRNAs. Our results provide a fresh insight into region-, development-stage-, and material-biased changes in lncRNA expression in the seeds of Brassica napus. Some of these lncRNAs may participate in the regulatory network of lipid accumulation and metabolism, together with regulated genes. These results may help elucidate the regulatory system of lncRNAs in the lipid metabolism of high-oleic-acid rapeseed seeds.

Anti-obesity mechanism of Ganpu tea revealed by microbiome, metabolome and transcriptome analyses.

In this study, the anti-obesity mechanism of Ganpu tea (GPT) from the perspectives of microbiome, metabolome and transcriptome was investigated. GPT significantly reduced the high-fat-diet (HFD)-induced levels of inflammatory cytokines and the expansion of lipid droplets and white adipose tissue. GPT also improved HFD-induced gut microbiome imbalance by significantly reducing the proportion of Firmicutes to Bacteroidota. Metabolomic data showed that HFD-induced metabolic disorder was regulated by GPT and probably characterised by being related to 4-aminobutyraldehyde and 5-acetylamino-6-amino-3-methyluracil. Transcriptome showed that the improvement of obesity was mainly related to the IL-17 signaling pathway and the metabolism of xenobiotics by cytochrome P450. Spearman's correlation analysis indicated that gut microbiota were significantly correlated with inflammatory factors, genes and metabolites. Metabolome-transcriptome analysis showed that GPT reversed obesity mainly through the carbohydrate metabolism, amino acid metabolism and lipid metabolism.Collectively, GPT may be used as a health drink to prevent or treat obesity.

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.

Porphyra haitanensis Polysaccharides Attenuates Blood Lipid via Gut-Liver Axis in Diet-Induced High-Fat Mesocricetus auratus through Multiple Integrated Omics.

SCOPE: Hyperlipidemia is currently a global public health problem severely affecting people's physical and mental health, as well as their quality of life. METHODS AND RESULTS: The present study is aimed at revealing the mechanism of Porphyra haitanensis polysaccharide (PHP) in decreasing blood lipids by acting through gut-liver axis in Mesocricetus auratus fed a high-fat diet. PHP significantly prevented increases in serum total cholesterol, triglycerides and low-density lipoprotein cholesterol, and alleviated damage to liver cells induced by a high-fat diet M. auratus, in a dose-dependent manner. PHP promotes proliferation of Muribaculaceae and Faecalibaculum, thereby enhancing the production of butyric acid both in the colon and liver, particularly high-dose PHP (HPHP). Low-dose PHP (LPHP) promotes the expression of phosphatidylcholine metabolites and fatty acid transport genes, and inhibits the expression of genes involved in fat degradation (Abhd5), adipogenesis (Me1), fatty acid synthesis (Fasn and Pnpla3), and fatty acid chain elongation (Elovl6) in the liver. However, HPHP inhibits the expression of triglyceride metabolites and promotes the expression of fatty acid transporter (CD36), fatty acid oxidation (Acacb), and peroxisome proliferator-activated receptor gamma (PPARg) genes in the liver. CONCLUSION: PHP regulates lipid metabolism through the gut microbiota, and the gut-liver axis plays an important role in its hypolipidemic effects.

[Sichuan Dark Tea-Based Medicated Dietary Formula Improves Obesity-Induced Renal Lipid Metabolism Disorder in Mice by Remodeling Gut Microbiota and Short-Chain Fatty Acid Metabolism]. / å››å·é»‘èŒ¶è¯è†³é æ–¹é€šè¿‡é‡å¡‘è‚ é“èŒç¾¤å’ŒçŸ­é“¾è„‚è‚ªé ¸ä»£è°¢æ”¹å–„è‚¥èƒ–å°é¼ è‚¾è„è„‚è´¨ç´Šä¹±.

Objective: To investigate the renoprotective effects of a Sichuan dark tea-based medicated dietary formula (alternatively referred to as Qing, or clarity in Chinese) on mice with diet-induced obesity (DIO) and to explore the specific mechanisms involved. Methods: Male C57BL/6 mice were randomly assigned to three groups, a control group, a DIO group, and a Qing treatment group, or the Qing group, with 8 mice in each group. The mice in the control group were given normal maintenance feed and purified water, and the other two groups were fed a high-fat diet for 12 weeks to establish the DIO model. After that, high-fat diet continued in the DIO group, while the Qing group was given Qing at the same time for 12 weeks, during which period the weight of the mice was monitored and recorded every week. The mice were sacrificed after 12 weeks. Serum samples were collected and the levels of triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin were measured to evaluate liver function. In addition, renal lipids were extracted to determine the levels of TG and TC in the kidney and periodic acid-Schiff (PAS) and oil red O stainings were performed to evaluate kidney pathological injury. Western blot was performed to determine the phosphorylated AMPK (pAMPK)/AMPK ratio in the kidney tissue. RT-qPCR and Western blot were used to determine the expression of proteins related to fatty acid oxidation, including acetyl-CoA carboxylase 1 (ACC1), carnitine acyltransferase 1 (CTP1), peroxisome proliferators-activated receptor γ (PPARγ), peroxisome proliferators-activated receptor-1 α (PPAR1α), sterol-regulatory element binding proteins (SREBP-1), and key proteins related to lipid synthesis, including fatty acid synthase (FASN) and stearoyl-coenzyme A desaturase 1 (stearoyl-CoA desaturase) in the kidney tissue. 16SrRNA and metabolomics were applied to analyze the gut microbiota in the intestinal contents and its metabolites. Results: Compared with those of the control group, the levels of liver mass (P=0.0003), serum ALT (P<0.0001) and AST (P=0.0001), and kidney TC (P=0.0191) and TG (P=0.0101) of the DIO group were significantly increased and there was lipid deposition in the kidney. Compared with those of the DIO group, mice in the Qing group showed effective reduction in liver mass (P=0.0316) and improvements in the abnormal serum levels of AST (P=0.0012) and ALT (P=0.0027) and kidney TC (P=0.0200) and TG (P=0.0499). In addition, mice in the Qing group showed significant improvement in lipid deposition in the kidney. Qing group showed increased pAMPK/AMPK ratio in comparison with that of the DIO group. In comparison with those of the control group, mice in the DIO group had upregulated expression of lipid synthesis-related genes and proteins (SREBP-1, FASN, and SCD1). As for the fatty acid oxidation-related genes and proteins, DIO mice showed upregulated expression of ACC1 and downregulated expression of CPT1A, PPARγ, and PGC1α in comparison with those of the control group. In the Qing goup, improvements in regard to all these changes were observed. The Qing group demonstrated improvement in the disrupted homeostasis of the gut microbiota. Short-chain fatty acids in the cecal contents, especially isovaleric acid and propionic acid, were also restored. Conclusion: Sichuan dark tea-based medicated dietary formula may improve renal lipid metabolism by regulating gut microbiota and the levels of intestinal short-chain fatty acids, thereby protecting obesity-related kidney injury. Isovaleric acid and propionic acid may be the metabolites key to its regulation of gut microbiota.

MiR-192-5p Ameliorates Hepatic Lipid Metabolism in Non-Alcoholic Fatty Liver Disease by Targeting Yy1.

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in the liver. Clarifying the molecular mechanism of lipid metabolism is crucial for the treatment of NAFLD. We examined miR-192-5p levels in the livers of mice in which NAFLD was induced via a high-fat diet (HFD), as well as in mouse primary hepatocytes and human HepG2 cells treated with free fatty acids (FFAs). MiR-192-5p inhibitor was administered to NAFLD mice and hepatocytes to verify the specific function of miR-192-5p in NAFLD. We validated the target gene of miR-192-5p and further illustrated the effects of this miRNA on the regulation of triglyceride (TG) metabolism. We found that miR-192-5p was significantly increased in the livers of NAFLD mice and FFA-treated hepatocytes. Inhibition of miR-192-5p increased the accumulation of hepatic TGs and aggravated hepatic steatosis in NAFLD mice. In FFA-treated hepatocytes, miR-192-5p inhibitors markedly increased TG content, whereas overexpression of miR-192-5p reduced TG levels. Yin Yang 1 (Yy1) was identified as the target gene of miR-192-5p, which regulates TG synthesis via the YY1/fatty-acid synthase (FASN) pathway. Our results demonstrated that miR-192-5p should be considered a protective regulator in NAFLD that can inhibit hepatic TG synthesis by targeting Yy1.

Resveratrol ameliorates oxidative stress, inflammatory response and lipid metabolism in common carp (Cyprinus carpio) fed with high-fat diet.

High-fat diet is regarded as crucial inducers of oxidative stress, inflammation, and metabolic imbalance. In order to investigate the ameliorative potential of resveratrol against the progression of liver injury towards steatohepatitis, common carp (Cyprinus carpio) were distributed into six experimental groups and were fed with a normal-fat diet, a high-fat diet, and supplemented with resveratrol (0.8, 1.6, 2.4, and 3.2 g/kg diet) for 8 weeks. The high-fat diet decreased the antioxidant capacities, as well as causing the inflammatory response and lipid deposition of common carp. Resveratrol induced a marked elevation in the final body weight, weight gain rate, condition factor and significant decrease in the feed conversion ratio. Moreover, dietary resveratrol showed a significant decrease in the alanine aminotransferase, aspartate aminotransferase, triglyceride and low-density lipoprotein levels, which was accompanied by an increase in high-density lipoprotein concentration in serum. A significant elevation in total superoxide dismutase, catalase, glutathione peroxidase and a decreased malondialdehyde content were observed, along with a substantial elevation in antioxidant activities were found. Additionally, fish fed with resveratrol had an up-regulation of hepatic catalase, copper, zinc superoxide dismutase, glutathione peroxidase 1a, and glutathione peroxidase 1b gene expression via Nrf2 signaling pathway. Expectedly, our results also demonstrated that resveratrol regulates hepatic lipid metabolism in fish by inhibiting the expression of hepatic lipogenesis genes (acetyl-CoA carboxylase 1, fatty acid synthase, and sterol regulatory element binding protein 1), fatty acid uptake-related genes of lipoprotein lipase, and ß-oxidation-related genes via PPAR-γ signaling pathway. Furthermore, dietary resveratrol reduced inflammation, as evident by down-regulating the interleukin-1ß, interleukin-6, interleukin-8, and tumor necrosis factor-α expression levels and upregulating the interleukin-10 and transforming growth factor-ß2 expression levels via NF-κB signaling pathway. As a whole, our results demonstrated that resveratrol defensed the impacts against high-fat diet on the serum biochemical, hepatic antioxidants, inflammation, and lipid metabolism.

miR-143-Mediated Responses to Betaine Supplement Repress Lipogenesis and Hepatic Gluconeogenesis by Targeting MAT1a and MAPK11.

The liver as the central organ is responsible for lipogenesis, gluconeogenesis and one-carbon metabolism. Methyl donors (e.g., betaine) modulate metabolic homeostasis and gene regulation through one-carbon metabolism. MiR-143 regulates DNA methylation by targeting DNMT3A, thereby suggesting that this miRNA participates in one-carbon metabolic pathways. However, the effect and mechanism that regulate glucose and lipid metabolism via the methyl group metabolism pathway remain elusive. In this study, we found that a betaine supplement and miR-143 KO significantly promoted lipolysis and glucose utilization and repressed lipogenesis and gluconeogenesis through enhancing energy consumption and thermogenesis, repressing GPNMB and targeting MAPK11, respectively. We further explored the relationship between miR-143 and a methyl donor (betaine) and the miR-143-mediated responses to the betaine supplement regulating the mechanism of the glucose and lipid metabolism. The results showed that betaine significantly down-regulated the expression of miR-143 that subsequently increased SAM levels in the liver by targeting MAT1a. In brief, the regulations of glucose and lipid metabolism are related to the miR-143-regulation of one-carbon units, and the relationship between betaine and miR-143 in the methionine cycle is a typical yin-yang type of regulation. Thus, betaine and miR-143 function together as key regulators and biomarkers for preventing and diagnosing metabolic diseases such as fatty liver disease, obesity, and diabetes.

High Iron Exposure from the Fetal Stage to Adulthood in Mice Alters Lipid Metabolism.

Iron supplementation is recommended during pregnancy and fetal growth. However, excess iron exposure may increase the risk of abnormal fetal development. We investigated the potential side effects of high iron levels in fetuses and through their adult life. C57BL/6J pregnant mice from 2 weeks of gestation and their offspring until 30 weeks were fed a control (CTRL, FeSO4 0 g/1 kg) or high iron (HFe, FeSO4 9.9 g/1 kg) diets. HFe group showed higher iron accumulation in the liver with increased hepcidin, reduced TfR1/2 mRNAs, and lowered ferritin heavy chain (FTH) proteins in both liver and adipose tissues despite iron loading. HFe decreased body weight, fat weight, adipocyte size, and triglyceride levels in the blood and fat, along with downregulation of lipogenesis genes, including PPARγ, C/EBPα, SREBP1c, FASN, and SCD1, and fatty acid uptake and oxidation genes, such as CD36 and PPARα. UCP2, adiponectin, and mRNA levels of antioxidant genes such as GPX4, HO-1, and NQO1 were increased in the HFe group, while total glutathione was reduced. We conclude that prolonged exposure to high iron from the fetal stage to adulthood may decrease fat accumulation by altering ferritin expression, adipocyte differentiation, and triglyceride metabolism, resulting in an alteration in normal growth.

Lotus seed resistant starch ameliorates high-fat diet induced hyperlipidemia by fatty acid degradation and glycerolipid metabolism pathways in mouse liver.

We investigated the potential efficacy and underlying mechanisms of Lotus seed Resistant Starch (LRS) for regulating hyperlipidemia in mice fed a High-fat Diet (HFD). Mouse were fed a normal diet (Normal Control group, NC group), HFD alone (MC group), HFD plus lovastatin (PC group), or HFD with low/medium/high LRS (LLRS, MLRS, and HLRS groups, respectively) for 4 weeks. LRS supplementation significantly decreased body weight and significantly reduced serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipopro-tein cholesterol compared with the MC group. LRS also significantly alleviated hepatic steatosis, especially in the MLRS group, which also showed a significantly reduced visceral fat index. LLRS supplementation significantly regulated genes associated with glycerolipid metabolism and steroid hormone biosynthesis (Lpin1 and Ugt2b38), MLRS significantly regulated genes related to fatty acid degradation, fatty acid elongation, and glycerolipid metabolism (Lpin1, Hadha, Aldh3a2, and Acox1), whereas HLRS significantly regulated genes related to fatty acid elongation and glycerolipid metabolism (Lpin1, Elovl3, Elovol5, and Agpat3). The fatty acid-degradation pathway regulated by MLRS thus exerts better control of serum lipid levels, body weight, visceral fat index, and liver steatosis in mice compared with LLRS- and HLRS-regulated pathways.

Comparative Proteomic Analysis Revealed the Mechanism of Tea Tree Oil Targeting Lipid Metabolism and Antioxidant System to Protect Hepatopancreatic Health in Macrobrachium rosenbergii.

Tea tree oil (TTO) is a pure natural plant essential oil. The studies evaluated the hepatopancreas lipid metabolism and antioxidant efficacy of Macrobrachium rosenbergii fed with 0 (CT group) and 100 mg/kg TTO (TT group) by label-free quantification proteomic analysis. Compared to the CT group, the TT group improved growth performance and increased the survival rate after stress. Dietary TTO also decreased hemolymph AST and ALT activities and decreased hepatopancreatic vacuolation. At the same time, hepatopancreas lipids droplets and hemolymph lipids (TG, TC, LDL-C) were decreased, and the peroxidation products content (MDA, LPO, 4-HNE) was also decreased. In addition, the levels of hepatopancreas antioxidant enzymes (T-AOC, CAT, and SOD) were increased in the TT group. With proteomic analysis, a total of 151 differentially expressed proteins (DEPs) (99 up-regulated and 52 down-regulated) were identified in the hepatopancreas. Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction analysis showed that the 16 DEPs have interactions, which are mainly involved in the pathways related to lipid metabolism (fatty acid biosynthesis, fatty acid metabolism, glycerophospholipid metabolism) and redox reaction (cytochrome P450 enzyme systems). Furthermore, the mRNA expression of 15 proteins followed the proteomic analysis with qRT-PCR validation. Pearson correlation analysis showed that fatty acids and glycerophospholipid metabolism-related proteins were highly correlated to peroxide content, glycerophospholipid metabolism, and cytochrome P450 system-related proteins (CYP1A1, GSTT1, GPX4) were highly correlated to AST and ALT. Additionally, GPX4 is closely related to peroxide content and antioxidant enzyme activity. Our results revealed that TTO plays a protective role in the hepatopancreas targeting the critical enzymes and antioxidant reactions in lipid metabolism. Provides a new perspective to elucidate the action path of TTO in protecting invertebrate hepatopancreas, highlights the influence of lipid metabolism on hepatopancreas health and the interaction between lipid metabolism and antioxidant system in the regulation of TTO.

Characterization and functional analysis of the MADS-box EgAGL9 transcription factor from the mesocarp of oil palm (Elaeis guineensis Jacq.).

Oil palm (Elaeis guineensis Jacq.) is one of the most important oil crops in the world, and compared to all oil crops, it has the highest productive efficiency. In the present study, a MADS-box transcription factor of the AGAMOUS class, named EgAGL9, was identified by expression profile analysis in the different developmental stages of oil palm mesocarp. Real-time quantitative PCR results confirmed that the expression of EgAGL9 increased rapidly during the last stages of oil palm mesocarp development. Then, three downstream genes, including EgSAD (Stearoyl-ACP desaturase), EgTSA (Tryptophan synthase) and EgSDH (Succinate dehydrogenase), were screened by ChIP-Seq and data analysis. EMSA analysis verified that EgAGL9 interacted with the promoter regions of EgSAD, EgTSA and EgSDH. Moreover, the expression levels of EgSAD, EgTSA and EgSDH were downregulated in EgAGL9-overexpressing protoplasts and calli of oil palm. Compared to WT, the total lipid content and ratio of unsaturated fatty acids in transgenic calli (including oleic acid, linoleic acid and linolenic acid) were significantly decreased. Together, these results revealed that these three EgAGL9-regulated genes are involved in regulatory pathways in the oil palm mesocarp. Compared with previous studies, the present study provides a new research strategy for understanding of the molecular regulatory pathways of lipid metabolism in mesocarp of oil palm. The obtained results will bring a new perspective for a comprehensive understanding of the regulation of the metabolic accumulation in the oil palm mesocarp.

Black Truffle Extract Exerts Antidiabetic Effects through Inhibition of Inflammation and Lipid Metabolism Regulation.

Black truffle, a culinary and medical fungus, is highly valued worldwide for its nutritional and therapeutic importance. To enhance the existing knowledge about the beneficial properties, this study investigates the antioxidant, antihyperlipidemic, and anti-inflammatory effects of black truffle extract in in vitro biochemical assays and animal study. Briefly, black truffle extract was administered orally to treat streptozotocin- (STZ-) induced diabetic Wistar rats for 45 days. At the end of the experimental duration, rats were sacrificed to perform biochemical and gene expression analyses related to lipid regulatory and inflammatory pathways. Our results indicated that total cholesterol, triglycerides, free fatty acids, phospholipids, and low-density lipoprotein in different tissues and circulation were significantly increased in diabetic rats. Furthermore, the ß-hydroxy ß-methylglutaryl-CoA enzyme was also significantly increased; lipoprotein lipase and lecithin-cholesterol acyltransferase enzymes were significantly decreased in diabetic rats. However, the above conditions were reversed upon black truffle extract feeding. Furthermore, black truffle extract was also found to downregulate the expression of proinflammatory cytokines (tumor necrosis factor-α and interleukin-6) and lipid regulatory genes (serum regulatory element-binding protein-1 and fatty acid synthase). The truffle extract-treated effects were comparable to glibenclamide and medication commonly used to treat diabetes mellitus. Overall, our results suggested that black truffle possesses strong antihyperlipidemic and anti-inflammatory effects on diabetic rats. These findings will enhance the current knowledge about the therapeutic importance of black truffles. They might be exploited as a possible food supplement or even as a natural source of pharmaceutical agents for diabetes prevention and treatment.

Tandem mass tag-based proteomics analysis of type 2 diabetes mellitus with non-alcoholic fatty liver disease in mice treated with acupuncture.

OBJECTIVE: To explore the proteomics profiles of hepatocytes of mice treated with acupuncture for type 2 diabetes mellitus (T2DM) with non-alcoholic fatty liver disease (NAFLD). METHODS: We used a Tandem mass tag (TMT)-based quantitative proteomics approach to identify proteins with potential molecular mechanisms associated with acupuncture interventions for T2DM with NAFLD. RESULTS: Acupuncture effectively improved body weight, blood glucose, and insulin levels in T2DM with NAFLD mouse models and reversed steatosis within hepatocytes. Quantitative TMT-based proteomics analysis identified a total of 4710 quantifiable proteins and 1226 differentially expressed proteins (DEPs) in the model control group (MCG) compared with the normal control group (NCG). The Acupuncture Treatment Group (ATG) presented in 122 DEPs was compared with the MCG group. We performed a bioinformatics analysis, which revealed that DEPs enriched in the KEGG pathway after acupuncture treatment were mainly involved in the PPAR signaling pathway, fatty acid biosynthesis, fatty acid metabolism, fatty acid elongation, fat digestion and absorption. We used parallel reaction monitoring (PRM) technology to explore the association of aldehyde oxidase 1 (Aox1), acyl-coenzyme A thioesterase 2 (Acot2), perilipin-2 (Plin2), acetyl-CoA carboxylase 1 (Acc), NADP-dependent malic enzyme (Me1), fatty acid synthase (Fasn), ATP-citrate synthase (Acly), fatty acid-binding protein, intestinal (Fabp2) with lipid synthesis, fatty acid oxidation, and hepatocyte steatosis. CONCLUSIONS: Our results show that acupuncture can regulate the protein expression of T2DM in the NAFLD mice model, and can effectively improve hepatocyte steatosis, and has potential benefits for the clinical treatment of this disease.