Cooked rice prevents hyperlipidemia in hamsters fed a high-fat/cholesterol diet by the regulation of the expression of hepatic genes involved in lipid metabolism.

Rice has many health-beneficial components for ameliorating obesity, diabetes, and dyslipidemia. However, the effect of cooked rice as a useful carbohydrate source has not been investigated yet; so we hypothesized that cooked rice may have hypolipidemic effects. In the present study, we investigated the effect of cooked rice on hyperlipidemia and on the expression of hepatic genes involved in lipid metabolism. Golden Syrian hamsters were divided into 2 groups and fed a high-fat (15%, wt/wt)/cholesterol (0.5%, wt/wt) diet supplemented with either corn starch (HFD, 54.5% wt/wt) or cooked rice (HFD-CR, 54.5% wt/wt) as the main carbohydrate source for 8 weeks. In the HFD-CR group, the triglyceride and total cholesterol levels in the serum and liver were decreased, and the total lipid, total cholesterol, and bile acid levels in the feces were increased, compared with the HFD group. In the cooked-rice group, the messenger RNA and protein levels of 3-hydroxy-3-methylglutaryl CoA reductase were significantly downregulated; and the messenger RNA and protein levels of the low-density lipoprotein receptor and cholesterol-7α-hydroxylase were upregulated. Furthermore, the expressions of lipogenic genes such as sterol response element binding protein-1, fatty acid synthase, acetyl CoA carboxylase, and stearoyl CoA desaturase-1 were downregulated, whereas the β-oxidation related genes (carnitine palmitoyl transferase-1, acyl CoA oxidase, and peroxisome proliferator-activated receptor α) were upregulated, in the cooked-rice group. Our results suggest that the hypolipidemic effect of cooked rice is partially mediated by the regulation of hepatic genes involved in lipid metabolism, which results in the suppression of cholesterol and fatty acid synthesis and the enhancement of cholesterol excretion and fatty acid β-oxidation.

Choi WH ，Gwon SY ，Ahn J ，Jung CH ，Ha TY ... -  《-》

Cooked rice inhibits hepatic fat accumulation by regulating lipid metabolism-related gene expression in mice fed a high-fat diet.

Choi WH ，Um MY ，Ahn J ，Jung CH ，Ha TY ... -  《-》

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 ... -  《-》

Dietary phosphate restriction induces hepatic lipid accumulation through dysregulation of cholesterol metabolism in mice.

Excessive inorganic phosphate (Pi) intake and hyperphosphatemia have both been speculated to be risk factors for cardiovascular disease and hypercholesterolemia, and dysregulation of cholesterol metabolism can lead to atherosclerosis. However, the relationship between Pi and cholesterol metabolism has not been investigated in detail. Our recent study showed that triiodothyronine can induce both hyperphosphatemia and hypocholesterolemia in mice. We therefore hypothesized a possible linkage between Pi and cholesterol metabolism. In this study, we investigated the effects of dietary Pi intake on cholesterol metabolism in mice. Mice were divided into 4 groups, which were fed diets containing 1.2% or 0.1% Pi and with or without 2% cholesterol (Pi-sufficient, Pi-restricted, Pi-sufficient + Chol, and Pi-restricted + Chol), for 12 days. Inorganic phosphate-restricted mice exhibited significantly higher liver weights than did Pi-sufficient mice. Interestingly, dietary Pi restriction significantly increased high-cholesterol diet-induced hepatic lipid accumulation. Real-time polymerase chain reaction analysis revealed that dietary Pi restriction decreased expression of hepatic genes involved in cholesterol metabolism and fatty acid biosynthesis. In addition, hepatic messenger RNA levels of several transcription factors including peroxisome proliferator-activated receptors and liver X receptor were markedly decreased by Pi restriction. Furthermore, plasma lipid and lipoprotein profile analysis showed that dietary Pi restriction reduced susceptibility to high-cholesterol diet-induced hyperlipidemia. Importantly, we found that there was a significant negative correlation between plasma levels of Pi and total cholesterol. These results suggest that dietary Pi plays an important role in the development of fatty liver disease and hyperlipidemia induced by a high-cholesterol diet through regulation of lipid metabolism-related gene expression in the liver.

Tanaka S ，Yamamoto H ，Nakahashi O ，Kagawa T ，Ishiguro M ，Masuda M ，Kozai M ，Ikeda S ，Taketani Y ，Takeda E ... -  《-》

Polyphenol-rich black chokeberry (Aronia melanocarpa) extract regulates the expression of genes critical for intestinal cholesterol flux in Caco-2 cells.

Black chokeberry (Aronia melanocarpa) is a rich source of polyphenols. The hypolipidemic effects of polyphenol-rich black chokeberry extract (CBE) have been reported, but underlying mechanisms have not been well characterized. We investigated the effect of CBE on the expression of genes involved in intestinal lipid metabolism. Caco-2 cells were incubated with 50 or 100 μg/ml of CBE for 24 h for quantitative realtime polymerase chain reaction analysis. Expression of genes for cholesterol synthesis (3-hydroxy-3-methylglutaryl coenzyme A reductase and sterol regulatory element binding protein 2), apical cholesterol uptake (Niemann-Pick C1 Like 1 and scavenger receptor class B Type 1) and basolateral cholesterol efflux [ATP-binding cassette transporter A1 (ABCA1)] was significantly decreased by CBE compared with control. Western blot analysis confirmed that CBE inhibited expression of these proteins. In contrast, CBE markedly induced mRNA and/or protein levels of ABCG5 and ABCG8 that mediate apical cholesterol efflux to the intestinal lumen. Furthermore, CBE significantly increased mRNA and protein levels of low-density lipoprotein (LDL) receptor, and cellular LDL uptake. Expression of genes involved in lipid metabolism and lipoprotein assembly, including sterol regulatory element-binding protein 1c, fatty acid synthase and acyl-CoA oxidase 1, was significantly decreased by CBE in a dose-dependent manner. Concomitantly, CBE significantly increased sirtuin 1, 3 and 5 mRNA levels, while it decreased SIRT-2. Our data suggest that hypolipidemic effects of CBE may be attributed, at least in part, to increased apical efflux of LDL-derived cholesterol and to decreased chylomicron formation in the intestine; and specific isoforms of SIRT may play an important role in this process.

Kim B ，Park Y ，Wegner CJ ，Bolling BW ，Lee J ... -  《-》