Podszun Maren C, Grebenstein Nadine, Spruss Astrid, Schlueter Thomas, Kremoser Claus, Bergheim Ina, Frank Jan
Institute of Biological Chemistry and Nutrition, University of Hohenheim, D-70599 Stuttgart, Germany.
Institute of Nutrition, University of Jena, D-07743 Jena, Germany.
J Nutr Biochem. 2014 May;25(5):573-9. doi: 10.1016/j.jnutbio.2014.01.008. Epub 2014 Feb 20.
The increased uptake and storage of lipids in the liver are important features of steatotic liver diseases. The fatty acid translocase/scavenger receptor cluster of differentiation (CD)36 facilitates the hepatic uptake of lipids. We investigated if RRR-α-tocopherol (αT) alone or in combination with atorvastatin (ATV) is capable of preventing hepatic lipid accumulation via down-regulation of CD36. To this end, Dunkin Hartley guinea pigs were fed a control diet (5% fat); or a high-fat control diet (21% fat, 0.15% cholesterol); or a high-fat control diet fortified with αT (250 mg/kg diet), ATV (300 mg/kg diet) or both ATV+αT for 6 weeks. Hepatic triacylglycerols, hepatic protein and mRNA expression of CD36 as well as the mRNA expression of the controlling nuclear receptors LXRα, PXR and PPARγ were determined. Animals fed the high-fat control diet accumulated significantly more triacylglycerols in the liver than control animals. This was significantly reduced by ATV and numerically by αT and ATV+αT. Hepatic CD36 protein concentrations were significantly higher in the high-fat than in the control group, and both αT and ATV reduced CD36 expression to the level observed in the control group. However, no synergistic effect of the combined treatment was observed. Neither CD36 mRNA nor that of the nuclear receptors (LXRα, PXR and PPARγ) differed between groups, suggesting a posttranslational regulatory mechanism. Our results indicate that orally administered ATV and αT individually, but not synergistically, prevent diet-induced lipid accumulation in the liver of guinea pigs by down-regulation of hepatic CD36 protein.
肝脏中脂质摄取和储存的增加是脂肪性肝病的重要特征。脂肪酸转运蛋白/分化簇（CD）36清道夫受体促进肝脏对脂质的摄取。我们研究了RRR-α-生育酚（αT）单独使用或与阿托伐他汀（ATV）联合使用是否能够通过下调CD36来预防肝脏脂质蓄积。为此，将Dunkin Hartley豚鼠分为以下几组喂养6周：对照组饮食（5%脂肪）；高脂对照组饮食（21%脂肪，0.15%胆固醇）；添加αT（250 mg/kg饮食）、ATV（300 mg/kg饮食）或两者联合（ATV+αT）的高脂对照组饮食。测定肝脏三酰甘油、CD36的肝脏蛋白和mRNA表达以及调控性核受体肝X受体α（LXRα）、孕烷X受体（PXR）和过氧化物酶体增殖物激活受体γ（PPARγ）的mRNA表达。喂食高脂对照组饮食的动物肝脏中积累的三酰甘油显著多于对照组动物。ATV可显著降低其水平，αT和ATV+αT在数值上也有降低。高脂组肝脏CD36蛋白浓度显著高于对照组，αT和ATV均将CD36表达降低至对照组水平。然而，未观察到联合治疗的协同效应。各组之间CD36 mRNA以及核受体（LXRα、PXR和PPARγ）的mRNA均无差异，提示存在翻译后调控机制。我们的结果表明，口服ATV和αT可分别而非协同地通过下调肝脏CD36蛋白来预防豚鼠饮食诱导的肝脏脂质蓄积。
