scholarly journals Coumarin attenuates hepatic steatosis by down-regulating lipogenic gene expression in mice fed a high-fat diet

2013 ◽  
Vol 109 (9) ◽  
pp. 1590-1597 ◽  
Author(s):  
Min Young Um ◽  
Mi Kyeong Moon ◽  
Jiyun Ahn ◽  
Tae Youl Ha
Keyword(s):  
Gene Expression ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
Binding Protein ◽  
Regulatory Element ◽  
Thiobarbituric Acid Reactive Substance ◽  
High Fat ◽  
Lipogenic Gene ◽  
Lipogenic Gene Expression

Coumarin is a natural compound abundant in plant-based foods such as citrus fruits, tomatoes, vegetables and green tea. Although coumarin has been reported to exhibit anti-coagulant, anti-inflammation and cholesterol-lowering properties, the effect of coumarin on hepatic lipid metabolism remains unclear. In the present study, we evaluated the ability of coumarin to protect against hepatic steatosis associated with a high-fat diet (HFD) and investigated potential mechanisms underlying this effect. C57BL/6J mice were fed a normal diet, HFD and HFD containing 0·05 % courmarin for 8 weeks. The present results showed that coumarin reduced weight gain and abdominal fat mass in mice fed the HFD for 8 weeks (P< 0·05). Coumarin also significantly reduced the HFD-induced elevation in total cholesterol, apoB, leptin and insulin (P< 0·05). In the liver of HFD-fed mice, coumarin significantly reduced total lipids, TAG and cholesterol (38, 22 and 9 % reductions, respectively; P< 0·05), as well as lipid droplet number and size. Additionally, thiobarbituric acid-reactive substance levels, as an indicator of hepatic steatosis, were attenuated by coumarin (P< 0·05). Finally, coumarin suppressed the HFD-induced up-regulation in fatty acid synthase (FAS) activity, and the expression of sterol regulatory element-binding protein-1, FAS, acetyl-CoA carboxylase 1, PPARγ and CCAAT/enhancer-binding protein-α in the liver. Taken together, these results demonstrate that coumarin could prevent HFD-induced hepatic steatosis by regulating lipogenic gene expression, suggesting potential targets for preventing hepatic steatosis.

scholarly journals Ishige okamurae Extract Suppresses Obesity and Hepatic Steatosis in High Fat Diet-Induced Obese Mice

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1802 ◽  
Author(s):  
Young-Jin Seo ◽  
Kippeum Lee ◽  
Ji-Hyeon Song ◽  
Sungwoo Chei ◽  
Boo-Yong Lee
Keyword(s):  
Fatty Acid ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
Metabolic Diseases ◽  
Binding Protein ◽  
Regulatory Element ◽  
Hormone Sensitive Lipase ◽  
High Fat ◽  
Ishige Okamurae

Obesity is caused by the expansion of white adipose tissue (WAT), which stores excess triacylglycerol (TG), this can lead to disorders including type 2 diabetes, atherosclerosis, metabolic diseases. Ishige okamurae extract (IOE) is prepared from a brown alga and has anti-oxidative properties. We investigated the detailed mechanisms of the anti-obesity activity of IOE. Treatment with IOE blocked lipid accumulation by reducing expression of key adipogenic transcription factors, such as CCAAT/enhancer-binding protein alpha (C/EBPα) and peroxisome proliferator-activated receptor gamma (PPARγ), in 3T3-L1 cells. Administration of IOE to high fat diet (HFD)-fed mice inhibited body and WAT mass gain, attenuated fasting hyperglycemia and dyslipidemia. The obesity suppression was associated with reductions in expression of adipogenic proteins, such as C/EBPα and PPARγ, increases in expression of lipolytic enzymes, such as adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), in WAT of HFD-fed mice. In addition, IOE-treated mice had lower hepatic TG content, associated with lower protein expression of lipogenic genes, such as diglyceride acyltransferase 1 (DGAT1), sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS). IOE treatment also reduced serum free fatty acid concentration, probably through the upregulation of β-oxidation genes, suggested by increases in AMPKα and CPT1 expression in WAT and liver. In summary, IOE ameliorates HFD-induced obesity and its related metabolic disease, hepatic steatosis, by regulating multiple pathways.

Ezetimibe prevents hepatic steatosis induced by a high-fat but not a high-fructose diet

2013 ◽  
Vol 305 (2) ◽  
pp. E293-E304 ◽  
Author(s):  
Masateru Ushio ◽  
Yoshihiko Nishio ◽  
Osamu Sekine ◽  
Yoshio Nagai ◽  
Yasuhiro Maeno ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
Binding Protein ◽  
High Fat ◽  
High Fructose Diet ◽  
High Fructose ◽  
Element Binding Protein

Nonalcoholic fatty liver disease is the most frequent liver disease. Ezetimibe, an inhibitor of intestinal cholesterol absorption, has been reported to ameliorate hepatic steatosis in human and animal models. To explore how ezetimibe reduces hepatic steatosis, we investigated the effects of ezetimibe on the expression of lipogenic enzymes and intestinal lipid metabolism in mice fed a high-fat or a high-fructose diet. CBA/JN mice were fed a high-fat diet or a high-fructose diet for 8 wk with or without ezetimibe. High-fat diet induced hepatic steatosis accompanied by hyperinsulinemia. Treatment with ezetimibe reduced hepatic steatosis, insulin levels, and glucose production from pyruvate in mice fed the high-fat diet, suggesting a reduction of insulin resistance in the liver. In the intestinal analysis, ezetimibe reduced the expression of fatty acid transfer protein-4 and apoB-48 in mice fed the high-fat diet. However, treatment with ezetimibe did not prevent hepatic steatosis, hyperinsulinemia, and intestinal apoB-48 expression in mice fed the high-fructose diet. Ezetimibe decreased liver X receptor-α binding to the sterol regulatory element-binding protein-1c promoter but not expression of carbohydrate response element-binding protein and fatty acid synthase in mice fed the high-fructose diet, suggesting that ezetimibe did not reduce hepatic lipogenesis induced by the high-fructose diet. Elevation of hepatic and intestinal lipogenesis in mice fed a high-fructose diet may partly explain the differences in the effect of ezetimibe.

scholarly journals Human Sterol Regulatory Element-Binding Protein 1a Contributes Significantly to Hepatic Lipogenic Gene Expression

2015 ◽  
Vol 35 (2) ◽  
pp. 803-815 ◽  
Author(s):  
Andreas Bitter ◽  
Andreas K. Nüssler ◽  
Wolfgang E. Thasler ◽  
Kathrin Klein ◽  
Ulrich M. Zanger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Liver ◽  
Target Genes ◽  
Binding Protein ◽  
Regulatory Element ◽  
Lipogenic Gene ◽  
Knock Down ◽  
Lipogenic Gene Expression ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Background/Aims: Sterol regulatory element-binding protein (SREBP) 1, the master regulator of lipogenesis, was shown to be associated with non-alcoholic fatty liver disease, which is attributed to its major isoform SREBP1c. Based on studies in mice, the minor isoform SREBP1a is regarded as negligible for hepatic lipogenesis. This study aims to elucidate the expression and functional role of SREBP1a in human liver. Methods: mRNA expression of both isoforms was quantified in cohorts of human livers and primary human hepatocytes. Hepatocytes were treated with PF-429242 to inhibit the proteolytic activation of SREBP precursor protein. SREBP1a-specifc and pan-SREBP1 knock-down were performed by transfection of respective siRNAs. Lipogenic SREBP-target gene expression was analyzed by real-time RT-PCR. Results: In human liver, SREBP1a accounts for up to half of the total SREBP1 pool. Treatment with PF-429242 indicated SREBP-dependent auto-regulation of SREBP1a, which however was much weaker than of SREBP1c. SREBP1a-specifc knock-down also reduced significantly the expression of SREBP1c and of SREBP-target genes. Regarding most SREBP-target genes, simultaneous knock-down of both isoforms resulted in effects of only similar extent as SREBP1a-specific knock-down. Conclusion: We here showed that SREBP1a is significantly contributing to the human hepatic SREBP1 pool and has a share in human hepatic lipogenic gene expression.

scholarly journals Gynostemma Pentaphyllum Extract Ameliorates High-Fat Diet-Induced Obesity in C57BL/6N Mice by Upregulating SIRT1

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2475 ◽  
Author(s):  
Hyun Sook Lee ◽  
Su-Min Lim ◽  
Jae In Jung ◽  
So Mi Kim ◽  
Jae Kyoung Lee ◽  
...  
Keyword(s):  
Body Weight ◽  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
Binding Protein ◽  
Regulatory Element ◽  
Control Diet ◽  
Sirtuin 1 ◽  
Hormone Sensitive Lipase ◽  
High Fat ◽  
Gynostemma Pentaphyllum

Gynostemma pentaphyllum is widely used in Asia as a herbal medicine to treat type 2 diabetes, dyslipidemia, and inflammation. Here, we investigated the anti-obesity effect and underlying mechanism of G. pentaphyllum extract (GPE) enriched in gypenoside L, gypenoside LI, and ginsenoside Rg3 and obtained using a novel extraction method. Five-week-old male C57BL/6N mice were fed a control diet (CD), high-fat diet (HFD), HFD + 100 mg/kg body weight (BW)/day GPE (GPE 100), HFD + 300 mg/kg BW/day GPE (GPE 300), or HFD + 30 mg/kg BW/day Orlistat (Orlistat 30) for 8 weeks. The HFD-fed mice showed significant increases in body weight, fat mass, white adipose tissue, and adipocyte hypertrophy compared to the CD group; but GPE inhibited those increases. GPE reduced serum levels of triglyceride, total cholesterol, and LDL-cholesterol, without affecting HDL-cholesterol. GPE significantly increased AMPK activation and suppressed adipogenesis by decreasing the mRNA expression of CCAAT/enhancer binding protein-α (C/EBPα), peroxisome proliferator-activated receptor-γ (PPARγ), sterol regulatory element-binding protein-1c (SREBP1c), PPARγ coactivator-1α, fatty acid synthase (FAS), adipocyte protein 2 (AP2), and sirtuin 1 (SIRT1) and by increasing that of carnitine palmitoyltransferase (CPT1) and hormone- sensitive lipase (HSL). This study demonstrated the ameliorative effect of GPE on obesity and elucidated the underlying molecular mechanism.

scholarly journals Combination of Limosilactobacillus fermentum MG4231 and MG4244 attenuates lipid accumulation in high-fat diet-fed obese mice

2021 ◽  
pp. 1-14
Author(s):  
S.J. Kim ◽  
S.-I. Choi ◽  
M. Jang ◽  
Y.-A. Jeong ◽  
C.-H. Kang ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Liver Tissue ◽  
Fatty Acid Synthase ◽  
Body Weight Gain ◽  
Binding Protein ◽  
Regulatory Element ◽  
Peroxisome Proliferator ◽  
Obese Mice ◽  
High Fat ◽  
Hepatic Atrophy

We investigated the anti-obesity effect and the underlying mechanisms of action of human-derived Limosilactobacillus fermentum MG4231, MG4244, and their combination, in high-fat diet-induced obese mice. Administration of the Limosilactobacillus strains decreased body weight gain, liver and adipose tissue weight, and glucose tolerance. Serum levels of total cholesterol, low-density lipoprotein-cholesterol, and leptin were reduced, while adiponectin increased. The administration of Limosilactobacillus strains improved the histopathological features of liver tissue, such as hepatic atrophy and inflammatory penetration, and significantly reduced the content of triglyceride in the liver. Limosilactobacillus administration discovered a significant reduction in the size of the adipocytes in the epididymal tissue. Limosilactobacillus treatment significantly reduced the expression of important regulators in lipid metabolism, including peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α, fatty acid synthase (FAS), adipocyte-protein 2, and lipoprotein lipase in the epididymal tissue. Also, Limosilactobacillus lowered sterol regulatory element-binding protein 1-c and FAS in the liver tissue. Such changes in the expression of these regulators in both liver and epididymis tissue were caused by Limosilactobacillus upregulating phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase. Therefore, we suggest that the use of the combination of L. fermentum MG4231 and MG4244, as probiotics could effectively inhibit adipogenesis and lipogenesis from preventing obesity.

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