Secreted modular calcium-binding protein 2 promotes high fat diet (HFD)-induced hepatic steatosis through enhancing lipid deposition, fibrosis and inflammation via targeting TGF-β1

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.

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

British Journal Of Nutrition ◽

10.1017/s0007114512005260 ◽

2013 ◽

Vol 109 (9) ◽

pp. 1590-1597 ◽

Cited By ~ 23

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.

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

Nutrients ◽

10.3390/nu10111802 ◽

2018 ◽

Vol 10 (11) ◽

pp. 1802 ◽

Cited By ~ 10

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.

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Lycopene inhibits hepatic steatosis via microRNA-21-induced downregulation of fatty acid-binding protein 7 in mice fed a high-fat diet

Molecular Nutrition & Food Research ◽

10.1002/mnfr.201200182 ◽

2012 ◽

Vol 56 (11) ◽

pp. 1665-1674 ◽

Cited By ~ 66

Author(s):

Jiyun Ahn ◽

Hyunjung Lee ◽

Chang Hwa Jung ◽

Taeyoul Ha

Keyword(s):

Fatty Acid ◽

Hepatic Steatosis ◽

High Fat Diet ◽

Fatty Acid Binding Protein ◽

Binding Protein ◽

High Fat ◽

Fatty Acid Binding ◽

Acid Binding Protein

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α-Linolenic Acid-Enriched Cold-Pressed Perilla Oil Suppress High-Fat Diet-Induced Hepatic Steatosis through Amelioration of the ER Stress-Mediated Autophagy

Molecules ◽

10.3390/molecules25112662 ◽

2020 ◽

Vol 25 (11) ◽

pp. 2662 ◽

Cited By ~ 1

Author(s):

Su Ji Bae ◽

Ji Eun Kim ◽

Hyeon Jun Choi ◽

Yun Ju Choi ◽

Su Jin Lee ◽

...

Keyword(s):

Fatty Acid ◽

Er Stress ◽

Hepatic Steatosis ◽

Linolenic Acid ◽

High Fat Diet ◽

Binding Protein ◽

Treated Group ◽

High Fat ◽

Perilla Oil ◽

Cold Pressed

Perilla oil has been considered to have excellent potential for treating various diseases due to its contents of beneficial fatty acids, such as α-linolenic acid, oleic acid and linoleic acid. The therapeutic effects and molecular mechanism of an α-linolenic acid-enriched cold-pressed perilla oil (LEP) on hepatic steatosis of an obesity model were investigated by analyzing alterations in fat accumulation and endoplasmic reticulum (ER) stress-mediated autophagy, in high-fat diet (HFD)-induced obesity C57BL/6N mice treated with LEP for 16 weeks. Although no significant alterations were detected in body weight and most organ weights, the liver weight and accumulation of lipid droplets in the liver section were significantly lower in HFD + LEP treated group as compared to the HFD + Vehicle treated group. Reduced mRNA expression levels of adipogenesis and lipogenesis regulating factors, including the peroxisome proliferator-activated receptor (PPAR)γ, CCAAT/enhancer-binding protein (C/EBP)α, fatty acid synthase (FAS), and adipocyte fatty acid-binding protein 2 (aP2) were observed after LEP treatment for 16 weeks, while the levels of lipolysis were remarkably increased in the same group. Moreover, the LEP-treated groups showed suppression of ER stress-regulating factors, such as the C/EBP homologous protein (CHOP), eukaryotic translation initiation factor 2α (eIF2α), inositol-requiring protein 1 (IRE1)α, and Jun-N-terminal kinase (JNK) during anti-hepatic steatosis effects. The expression level of the microtubule-associated protein 1A/1B-light chain 3 (LC3) protein and phosphatidylinositol-3-kinase (PI3K)/AKT/ mammalian target of rapamycin (mTOR) pathway for the autophagy response showed a significant decrease in the HFD+LEP-treated group. Furthermore, ER stress-mediated autophagy was accompanied with enhanced phosphorylation of extracellular signal-regulated kinase (ERK), JNK, and p38 protein in the mitogen-activated protein (MAP) kinase signaling pathway. Taken together, the results of the present study indicate that treatment with LEP inhibits hepatic steatosis in the HFD-induced obese model through regulation of adipogenesis and lipolysis. We believe our results are the first to show that the anti-hepatic steatosis activity of α-linolenic acid from cold-pressed perilla oil might be tightly correlated with the amelioration of ER stress-mediated autophagy.

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