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 ... -  《-》

Oxymatrine ameliorates non-alcoholic fatty liver disease in rats through peroxisome proliferator-activated receptor-α activation.

Shi L ，Shi L ，Zhang H ，Hu Z ，Wang C ，Zhang D ，Song G ... -  《-》

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 ... -  《-》

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 ... -  《-》

Genistein has beneficial effects on hepatic steatosis in high fat-high sucrose diet-treated rats.

Genistein, a kind of phytoestrogen abundant in soybeans, is beneficial for alleviating non-alcoholic fatty liver disease (NAFLD), but the specific mechanism was not clearly understood. This study was designed to determine the effect of genistein on NAFLD and explore the possible mechanism. 36 male Sprague-Dawley rats were divided into 4 groups: the control group, high fat-high sucrose diet (HFS) group, HFS with 4mg/kg body weight genistein, and HFS with 8mg/kg body weight genistein. 12 weeks later, serum and hepatic lipid profiles, liver histopathological examination were characterized. The protein levels of liver AMP-activated protein kinase (AMPK), phosphorylation of AMPK (p-AMPK), acetyl-CoA carboxylase (ACC), phosphorylation of ACC (p-ACC) and sterol regulatory element binding protein 1 (SREBP-1) were determined by western blot. mRNA expressions of fatty acid synthase gene (FAS) and glycerol-3-phosphate acyltransferase (GPAT), peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyl transfer enzyme-1 (CPT-1) and acyl-CoA oxidase (ACO) were measured by reverse transcription polymerase chain reaction (RT-PCR). Results showed that genistein effectively improved serum and hepatic lipid metabolism and diminished fat accumulation in liver. And the protein level of hepatic p-AMPK and p-ACC were increased, but SREBP-1 was decreased by genistein. Meanwhile, the mRNA levels of FAS and GPAT were lower, but PPARα, CPT-1, ACO were higher in rats treated with genistein compared with HFS group. Collectively, genistein can improve hepatic steatosis via activating AMPK, thus promoting fatty acid oxidation and inhibiting lipid synthesis in liver.

Liu H ，Zhong H ，Yin Y ，Jiang Z ... -  《-》