scholarly journals The Effects of New Selective PPARα Agonist CP775146 on Systematic Lipid Metabolism in Obese Mice and Its Potential Mechanism

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Shengjie Tang ◽  
Fang Wu ◽  
Xihua Lin ◽  
Weiwei Gui ◽  
Fenping Zheng ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Uncoupling Protein ◽  
Density Lipoprotein ◽  
Hormone Sensitive Lipase ◽  
Lipoprotein Cholesterol ◽  
Obese Mice ◽  
Liver Fatty Acid ◽  
Expression Of Genes

Purpose. Peroxisome proliferator-activated receptor α (PPARα) plays a crucial role in the control of lipid homeostasis. Here, we investigated the effects of CP775146, a new selective PPARα agonist, on lipid metabolism in diet-induced obese mice and its possible mechanism. Methods. C57BL/6 mice were fed a high-fat diet (HFD) for 12 weeks to induce obesity and then received CP775146 via intraperitoneal injection for 3 days. The content/morphology of the liver, serum lipid, and liver function was measured. The expression of genes related to lipolysis and synthesis in liver was detected by quantitative real-time PCR (qRT-PCR). Results. The safe dose of CP775146 was <0.3 mg/kg. CP775146 reduced the serum levels of liver enzymes, such as alanine aminotransferase (ALT) and glutamic-oxaloacetic transaminase (AST) and lipid metabolism-related biomarkers, including triglycerides (TGs) and low-density lipoprotein cholesterol (LDL-c), non-high-density lipoprotein cholesterol (non-HDL-c), and hepatic TG content, at a dosage of 0.1 mg/kg. HFD-induced pathological liver changes improved after CP775146 treatment. The expression of genes involved in liver fatty acid oxidation (acyl-coenzyme A dehydrogenase, long chain (Acadl), acyl-CoA oxidase 1 (Acox-1), carnitine palmitoyltransferase-1 (CPT-1), and enoyl-CoA, hydratase/3-hydroxyacyl CoA dehydrogenase (Ehhadh)) was upregulated in CP775146-treated mice. Furthermore, CP775146 induced the expression of thermogenesis genes (cell death-inducing DFFA-like effector a (Cidea), uncoupling protein 1 (Ucp1)) and lipolysis genes (hormone-sensitive lipase (Hsl), adipose tissue triglyceride lipase (Atgl)) in epididymal white adipose tissue (eWAT), activating browning and thermogenesis. Conclusion. CP775146 efficiently alleviates obesity-induced liver damage, prevents lipid accumulation by activating the liver fatty acid β-oxidation pathway, and regulates the expression of genes that control brown fat-like pathway in eWAT.

scholarly journals ChREBP-Mediated Regulation of Lipid Metabolism: Involvement of the Gut Microbiota, Liver, and Adipose Tissue

2020 ◽  
Vol 11 ◽  
Author(s):  
Katsumi Iizuka ◽  
Ken Takao ◽  
Daisuke Yabe
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Gut Microbiota ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Acid Synthesis ◽  
Whole Body ◽  
Acetyl Coa ◽  
Alcoholic Fatty Liver

Carbohydrate response element-binding protein (ChREBP) plays an important role in the development of type 2 diabetes, dyslipidemia, and non-alcoholic fatty liver disease, as well as tumorigenesis. ChREBP is highly expressed in lipogenic organs, such as liver, intestine, and adipose tissue, in which it regulates the production of acetyl CoA from glucose by inducing Pklr and Acyl expression. It has recently been demonstrated that ChREBP plays a role in the conversion of gut microbiota-derived acetate to acetyl CoA by activating its target gene, Acss2, in the liver. ChREBP regulates fatty acid synthesis, elongation, and desaturation by inducing Acc1 and Fasn, elongation of long-chain fatty acids family member 6 (encoded by Elovl6), and Scd1 expression, respectively. ChREBP also regulates the formation of very low-density lipoprotein by inducing the expression of Mtp. Furthermore, it plays a crucial role in peripheral lipid metabolism by inducing Fgf21 expression, as well as that of Angptl3 and Angptl8, which are known to reduce peripheral lipoprotein lipase activity. In addition, ChREBP is involved in the production of palmitic-acid-5-hydroxystearic-acid, which increases insulin sensitivity in adipose tissue. Curiously, ChREBP is indirectly involved in fatty acid β-oxidation and subsequent ketogenesis. Thus, ChREBP regulates whole-body lipid metabolism by controlling the transcription of lipogenic enzymes and liver-derived cytokines.

scholarly journals Effects of an oral and intravenous fat load on adipose tissue and forearm lipid metabolism

1999 ◽  
Vol 276 (2) ◽  
pp. E241-E248 ◽  
Author(s):  
Kevin Evans ◽  
Mo L. Clark ◽  
Keith N. Frayn
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hormone Sensitive Lipase ◽  
Nonesterified Fatty Acid ◽  
Subcutaneous Adipose

We have studied the fate of lipoprotein lipase (LPL)-derived fatty acids by measuring arteriovenous differences across subcutaneous adipose tissue and skeletal muscle in vivo. Six subjects were fasted overnight and were then given 40 g of triacylglycerol either orally or as an intravenous infusion over 4 h. Intracellular lipolysis (hormone-sensitive lipase action; HSL) was suppressed after both oral and intravenous fat loads ( P < 0.001). Insulin, a major regulator of HSL activity, showed little change after either oral or intravenous fat load, suggesting that suppression of HSL action occurred independently of insulin. The rate of action of LPL (measured as triacylglycerol extraction) increased with both oral and intravenous fat loads in adipose tissue ( P = 0.002) and skeletal muscle ( P = 0.001). There was increased escape of LPL-derived fatty acids into the circulation from adipose tissue, shown by lack of reesterification of fatty acids. There was no release into the circulation of LPL-derived fatty acids from skeletal muscle. These results suggest that insulin is not essential for HSL suppression or increased triacylglycerol clearance but is important in reesterification of fatty acids in adipose tissue but not uptake by skeletal muscle, thus affecting fatty acid partitioning between adipose tissue and the circulation, postprandial nonesterified fatty acid concentrations, and hepatic very low density lipoprotein secretion.

scholarly journals Comparative Analysis of Metabolite Profiling of Momordica charantia Leaf and the Anti-Obesity Effect through Regulating Lipid Metabolism

2021 ◽  
Vol 18 (11) ◽  
pp. 5584
Author(s):  
Meiqi Fan ◽  
Jae-In Lee ◽  
Young-Bae Ryu ◽  
Young-Jin Choi ◽  
Yujiao Tang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipid Metabolism ◽  
High Fat Diet ◽  
Density Lipoprotein ◽  
Momordica Charantia ◽  
Lipoprotein Cholesterol ◽  
Distilled Water ◽  
High Fat ◽  
Leaf Extracts ◽  
Abnormal Lipid Metabolism

This study investigated the effects of Momordica charantia (M. charantia) extract in obesity and abnormal lipid metabolism in mice fed high fat diet (HFD). Fruit, root, stem, and leaf extracts of M. charantia were obtained using distilled water, 70% ethanol and 95% hexane. M. charantia leaf distilled water extract (MCLW) showed the highest antioxidant activity in both 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity tests and reducing power. Metabolite profiles of M. charantia leaf extracts were analyzed for identification of bioactive compounds. HFD-fed mice were treated with MCLW (oral dose of 200 mg/kg/d) for 4 weeks. MCLW reduced lipid accumulation, body weight, organ weight, and adipose tissue volume and significantly improved glucose tolerance and insulin resistance in HFD mice. Furthermore, MCLW administration reduced serum total cholesterol and low-density lipoprotein cholesterol, and increased serum high-density lipoprotein cholesterol compared with HFD mice. Moreover, MCLW significantly reduced the levels of serum urea nitrogen, alanine aminotransferase, alkaline phosphatase, and aspartate aminotransferase; alleviated liver and kidney injury. MCLW decreases expression of genes that fatty acid synthesis; increase the expression of catabolic-related genes. These results indicate that MCLW has an inhibitory effect on obese induced by high fat diet intake, and the mechanism may be related to the regulation of abnormal lipid metabolism in liver and adipose tissue, suggesting that MCLW may be a suitable candidate for the treatment of obesity.

scholarly journals The Crude Extract fromPuerariaeFlower Exerts Antiobesity and Antifatty Liver Effects in High-Fat Diet-Induced Obese Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Tomoyasu Kamiya ◽  
Mayu Sameshima-Kamiya ◽  
Rika Nagamine ◽  
Masahito Tsubata ◽  
Motoya Ikeguchi ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
High Fat Diet ◽  
Uncoupling Protein ◽  
Expression Profiles ◽  
Folk Medicine ◽  
Hormone Sensitive Lipase ◽  
Leguminous Plant ◽  
Obese Mice ◽  
High Fat ◽  
Brown Adipose

Kudzu, a leguminous plant, has long been used in folk medicine. In particular, its flowers are used in Japanese and Chinese folk medicine for treating hangovers. We focused on the flower of Kudzu (Puerariae thomsonii), and we previously reported the antiobesity effect ofPuerariae thomsoniiflower extract (PFE) in humans. In this study, we conducted an animal study to investigate the effect of PFE on visceral fat and hepatic lipid levels in mice with diet-induced obesity. In addition, we focused on gene expression profiles to investigate the antiobesity mechanism of PFE. Male C57BL/6J mice were fed a high-fat diet (HFD) or an HFD supplemented with 5% PFE for 14 days. PFE supplementation significantly reduced body weight and white adipose tissue (WAT) weight. Moreover, in the histological analysis, PFE supplementation improved fatty liver. Hepatic reverse transcription-polymerase chain reaction revealed that PFE supplementation downregulated acetyl-CoA carboxylase expression. For adipose tissue, the expressions of hormone-sensitive lipase in WAT and uncoupling protein 1 in brown adipose tissue (BAT) were significantly upregulated. These results suggest that PFE exerts antiobesity and antifatty liver effects in high-fat diet-induced obese mice through suppressing lipogenesis in the liver, stimulating lipolysis in WAT, and promoting thermogenesis in BAT.

Antihyperlipidemic and Hepatoprotective Properties of Vitamin B6 Supplementation in Rats with High-Fat Diet-Induced Hyperlipidemia

2021 ◽  
Vol 21 ◽  
Author(s):  
Qian Zhang ◽  
Da-long Zhang ◽  
Xiao-li Zhou ◽  
Qian Li ◽  
Ning He ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Protein Expression ◽  
High Fat Diet ◽  
Vitamin B6 ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherogenic Index ◽  
High Fat ◽  
Hepatic Lipid

Background: The incidence and mortality of hyperlipidemia are increasing year by year, showing a younger trend. At present, the treatment of hyperlipidemia is mainly dependent on western medicine, but its side effects on liver and kidney function are common in clinics. Therefore, it is necessary to study the treatment of hyperlipidemia by augmenting effective dietary nutrition supplements. Vitamin B6 (VitB6), as an essential cofactor for enzymes, participates in lipid metabolism. The effects of VitB6 on hyperlipidemia, however, have not been reported until now. Aim: The present study was to investigate the influence of VitB6 on hepatic lipid metabolism in hyperlipidaemia rats induced by a high-fat diet (HFD). Methods: Male Sprague-Dawley rats were kept on HFD for two weeks to establish the hyperlipidemia model. The rats in low-dosage and high-dosage groups were received 2.00 and 3.00 mg/kg/day of VitB6 for eight weeks, respectively. Results: The results showed that both doses of VitB6 reduced HFD-induced hepatic low-density lipoprotein cholesterol (LDL-C); decreased blood cholesterol (TC), triglycerides, LDL-C, atherogenic index (AI), atherogenic index of plasma (AIP), apolipoprotein B (ApoB) and ApoB/apolipoprotein A-1(ApoA1) ratio; increased liver high-density lipoprotein cholesterol (HDL-C) and serum ApoA1; reduced hepatic steatosis and triglyceride accumulation, lowered fat storage, and recovered heart/body and brain/body ratio to a normal level. In addition, VitB6 supplementation markedly decreased HMGR level, increased the mRNA abundance of LDLR and CYP7A1, and protein expression of SIRT1, following the downregulation of SREBP-1 and PPARγ protein expression in the liver of hyperlipidemia rats. Conclusion: In summary, oral VitB6 supplementation can ameliorate HFD-induced hepatic lipid accumulation and dyslipidemia in SD rats by inhibiting fatty acid and cholesterol synthesis, promoting fatty acid decomposition and cholesterol transport.

Conjugated Linoleic Acid (t-10, c-12) Reduces Fatty Acid Synthesis de Novo, but not Expression of Genes for Lipid Metabolism in Bovine Adipose Tissue ex Vivo

Lipids ◽  
2013 ◽  
Vol 49 (1) ◽  
pp. 15-24 ◽  
Author(s):  
Seong Ho Choi ◽  
David T. Silvey ◽  
Bradley J. Johnson ◽  
Matthew E. Doumit ◽  
Ki Yong Chung ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Linoleic Acid ◽  
Conjugated Linoleic Acid ◽  
Fatty Acid Synthesis ◽  
De Novo ◽  
Ex Vivo ◽  
Acid Synthesis ◽  
Expression Of Genes

scholarly journals Supplementation With Lycium barbarum Polysaccharides Reduce Obesity in High-Fat Diet-Fed Mice by Modulation of Gut Microbiota

2021 ◽  
Vol 12 ◽  
Author(s):  
Mei Yang ◽  
Yexin Yin ◽  
Fang Wang ◽  
Haihan Zhang ◽  
Xiaokang Ma ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Gut Microbiota ◽  
High Fat Diet ◽  
Density Lipoprotein ◽  
Short Chain ◽  
Lipoprotein Cholesterol ◽  
High Fat ◽  
Lycium Barbarum ◽  
Lycium Barbarum Polysaccharides

Lycium barbarum polysaccharides (LBPs) have been proved to prevent obesity and modulate gut microbiota. However, the underlying mechanisms of LBPs’ regulating lipid metabolism remain entirely unclear. Therefore, the purpose of this study was to determine whether LBPs are able to modulate the gut microbiota to prevent obesity. The results showed that oral administration of LBPs alleviated dyslipidemia by decreasing the serum levels of total triglycerides, total cholesterol, and low-density lipoprotein-cholesterol and elevating the high-density lipoprotein cholesterol in obese mice. Furthermore, LBP treatment decreased the number and size of adipocytes in epididymal adipose tissues and downregulated the expression of adipogenesis-related genes, including acetyl-CoA carboxylase 1, fatty acid synthase, stearoyl-CoA desaturase 1, sterol regulatory element-binding protein-1c, peroxisome proliferator-activated receptor γ, and CCAAT/enhancer-binding protein α. 16S rRNA gene sequencing analysis showed that LBPs increased the diversity of bacteria, reduced the Firmicutes/Bacteroidetes ratio, and improved the gut dysbiosis induced by a high-fat diet; for example, LBPs increased the production of short-chain fatty acid-producing bacteria Lacticigenium, Lachnospiraceae_NK4A136_group, and Butyricicoccus. LBPs treatment also increased the content of fecal short-chain fatty acids, including butyric acid. These findings illustrate that LBPs might be developed as a potential prebiotic to improve lipid metabolism and intestinal diseases.

scholarly journals Regulatory Roles of SREBF1 and SREBF2 in Lipid Metabolism and Deposition in Two Chinese Representative Fat-Tailed Sheep Breeds

Animals ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1317
Author(s):  
Chen Liang ◽  
Liying Qiao ◽  
Yongli Han ◽  
Jianhua Liu ◽  
Jianhai Zhang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Target Genes ◽  
Regulatory Element ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Triglyceride ◽  
Lipoprotein Cholesterol ◽  
Dependent Manner ◽  
And Function

Sterol regulatory element binding proteins (SREBPs) can regulate the lipid homeostasis by regulating its target genes, which are crucial for the cholesterol and fatty acid metabolism. However, the transcriptional regulation role of SREBPs in fat-tailed sheep is unclear. In this study, two Chinese representative breeds of total 80 fat-tailed sheep were employed, serum triglyceride, total cholesterol (TC), non-esterified fatty acid (NEFA), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and mRNA expressions of SREBF1 and SREBF2 in seven different adipose tissues and liver were examined in sheep at the ages of 4, 6, 8, 10, and 12 months, respectively. The subcellular localization and function of SREBP1/2 were predicted through bioinformatics approaches. The results demonstrated that serum TC and NEFA levels among breeds were significantly different, and most serum indices were dynamically altered in an age-dependent manner. The mRNA expression profiling of SREBF1 and SREBF2 are breed-specific with temporal and spatial expressions differences. Further analysis shows that SREBF1/2 transcriptional levels and tail traits are closely related. All investigations simplify that SREBF1/2 play a crucial role in lipid metabolism and deposition during growth and development of the fat-tailed sheep, which also provides a novel insight for revealing the genetic mechanism of different tail type and meat quality.

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