Vitamin D attenuates high fat diet-induced hepatic steatosis in rats by modulating lipid metabolism.

Vitamin D has been reported to be reversely associated with type 2 diabetes and metabolic syndrome and is involved in modulation of lipid metabolism. The purpose of the present study was to determine whether 1,25-dihydroxyvitamin D(3) (1,25(OH)(2) D(3) ) has a protective effect on high fat diet (HFD)-induced hepatic steatosis in rats and to elucidate its underlying molecular mechanisms. Male Sprague-Dawley (SD) rats were fed with normal fat diet, HFD or HFD with intraperitoneal injection of 1, 2.5 and 5 μg/kg 1,25(OH)(2) D(3) , respectively, each 2 days for 8 weeks. Serum lipid profile and liver triglyceride were determined. Hepatic histology was examined by haematoxylin/eosin (H&E) and Oil Red O stainings. Hepatic gene expression involved in lipogenesis and lipid oxidation was analysed by quantitative reverse transcription-polymerase chain reaction (RT-PCR). The administration of 1,25(OH)(2) D(3) prevented HFD-induced body weight gain and reduced liver weight. 1,25(OH)(2) D(3) attenuated hepatic steatosis in a dose-dependent manner along with improved serum lipid profile. Furthermore, 1,25(OH)(2) D(3) downregulated mRNA expression of sterol regulatory element binding protein-1c (SREBP-1c) and its target genes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) involved in lipogenesis. Peroxisome proliferator-activated receptor α (PPARα) and its target gene carnitine palmitoyltransferase-1 (CPT-1) involved in hepatic fatty acid (FA) oxidation were upregulated by 1,25(OH)(2) D(3) . These results suggest that the preventing effect of 1,25(OH)(2) D(3) against HFD-induced hepatic steatosis is related to the inhibition of lipogenesis and the promotion of FA oxidation in rat liver.

Yin Y ，Yu Z ，Xia M ，Luo X ，Lu X ，Ling W ... -  《-》

Beneficial effects of mangiferin on hyperlipidemia in high-fat-fed hamsters.

Mangiferin, a natural polyphenol, has been shown to have hypolipidemic effect in rat and mouse. However, the mechanism of action is not well understood. This study was conducted to determine the effect and mechanism of action of mangiferin on hyperlipidemia induced in hamsters by a high-fat diet. Forty male hamsters were randomly assigned to normal control, high-fat control, and high fat with mangiferin (50 and 150 mg/kg BW) groups. Mangiferin treatment significantly decreased final body weight, liver weight and visceral fat-pad weight, serum triglyceride (TG) and total free fatty acid (FFA) concentrations, hepatic TG levels and hepatic and muscle total FFA contents. Mangiferin upregulated mRNA expression of peroxisome proliferator-activated receptor-α (PPAR-α), fatty acid translocase (CD36) and carnitine palmitoyltransferase 1 (CPT-1), but downregulated mRNA expression of sterol regulatory element-binding protein 1c (SREBP-1c), acetyl CoA carboxylase (ACC), acyl-CoA:diacylglycerol acyltransferase 2 (DGAT-2) and microsomal triglyceride transfer protein (MTP) in liver. Mangiferin also stimulated mRNA expression of PPAR-α, CD36, CPT-1 and lipoprotein lipase (LPL) in muscle. The results suggest that mangiferin may ameliorate hypertriglyceridemia partly by modulating the expression levels of genes involved in lipid oxidation and lipogenesis.

Guo F ，Huang C ，Liao X ，Wang Y ，He Y ，Feng R ，Li Y ，Sun C ... -  《-》

Polydatin alleviates non-alcoholic fatty liver disease in rats by inhibiting the expression of TNF-α and SREBP-1c.

Zhang J ，Tan Y ，Yao F ，Zhang Q ... -  《-》

Modulation of hepatic sterol regulatory element-binding protein-1c-mediated gene expression contributes to Salacia oblonga root-elicited improvement of fructose-induced fatty liver in rats.

Salacia oblonga root (SOR) is a traditionally herbal medicine for obesity and diabetes, which are closely associated with fatty liver. To investigate the molecular mechanisms of SOR in the treatment of dietary-induced fatty liver. Male rats were co-administered with fructose in drinking water and vehicle or the aqueous-ethanolic extract of SOR (by gavage, once daily) for 10 weeks. Biochemical variables were determined enzymatically or by ELISA. Gene expression was analyzed by Real-Time PCR and/or Western blot. SOR treatment (20mg/kg) diminished fructose-induced fatty liver indicated by decreases in excess triglyceride accumulation and the increased vacuolization and Oil Red O staining area in the livers of rats. Importantly, Hepatic gene expression profile revealed that SOR suppressed fructose-stimulated overexpression of sterol regulatory element-binding protein (SREBP)-1/1c mRNA and nuclear protein. In accord, overexpression of SREBP-1c-responsive genes, such as fatty acid synthase, acetyl-CoA carboxylase-1 and stearoyl-CoA desaturase-1, was also downregulated. In contrast, overexpressed nuclear protein of carbohydrate response element binding protein and mRNA of its target gene liver pyruvate kinase were not altered. Additionally, SOR also did not affect expression of peroxisome proliferator-activated receptor-gamma- and -alpha, as well as their target genes, such as carnitine palmitoyltransferase-1a, acyl-CoA oxidase and CD36. These results suggest that modulation of hepatic sterol regulatory element-binding protein-1c-mediated gene expression contributes to SOR-elicited improvement of fructose-induced fatty liver in rats. Our findings provide a better understanding of SOR in the treatment of obesity and diabetes.

Liu L ，Yang M ，Lin X ，Li Y ，Liu C ，Yang Y ，Yamahara J ，Wang J ，Li Y ... -  《-》

Oxymatrine attenuates hepatic steatosis in non-alcoholic fatty liver disease rats fed with high fructose diet through inhibition of sterol regulatory element binding transcription factor 1 (Srebf1) and activation of peroxisome proliferator activated recep

The aim of this study was to examine the therapeutic effect of oxymatrine, a monomer isolated from the medicinal plant Sophora flavescens Ait, on the hepatic lipid metabolism in non-alcoholic fatty liver (NAFLD) rats and to explore the potential mechanism. Rats were fed with high fructose diet for 8 weeks to establish the NAFLD model, then were given oxymatrine treatment (40, 80, and 160 mg/kg, respectively) for another 8 weeks. Body weight gain, liver index, serum and liver lipids, and histopathological evaluation were measured. Enzymatic activity and gene expression of the key enzymes involved in the lipogenesis and fatty acid oxidation were assayed. The results showed that oxymatrine treatment reduced body weight gain, liver weight, liver index, dyslipidemia, and liver triglyceride level in a dose dependant manner. Importantly, the histopathological examination of liver confirmed that oxymatrine could decrease the liver lipid accumulation. The treatment also decreased the fatty acid synthase (FAS) enzymatic activity and increased the carnitine palmitoyltransferase 1A (CPT1A) enzymatic activity. Besides, oxymatrine treatment decreased the mRNA expression of sterol regulatory element binding transcription factor 1(Srebf1), fatty acid synthase (Fasn), and acetyl CoA carboxylase (Acc), and increased the mRNA expression of peroxisome proliferator activated receptor alpha (Pparα), carnitine palmitoyltransferase 1A (Cpt1a), and acyl CoA oxidase (Acox1) in high fructose diet induced NAFLD rats. These results suggested that the therapeutic effect of oxymatrine on the hepatic steatosis in high fructose diet induced fatty liver rats is partly due to down-regulating Srebf1 and up-regulating Pparα mediated metabolic pathways simultaneously.

Shi LJ ，Shi L ，Song GY ，Zhang HF ，Hu ZJ ，Wang C ，Zhang DH ... -  《-》