Gracia Ana, Fernández-Quintela Alfredo, Miranda Jonatan, Eseberri Itziar, González Marcela, Portillo María P
1Nutrition and Obesity Group, Department of Nutrition and Food Science, University of the Basque Country (UPV/EHU) and Lucio Lascaray Research Institute, Vitoria 01006, Spain;
Nutrients. 2017 Apr 4;9(4):360. doi: 10.3390/nu9040360.
The aim of the present study was to determine whether the reduction in liver fat previously observed in our laboratory in a cohort of rats which had been fed an obesogenic diet was mediated by changes in the expression of microRNA (miRNA)-103-3p, miRNA-107-3p and miRNA-122-5p, which represent 70% of total miRNAs in the liver, as well as in their target genes. The expression of the three analysed miRNAs was reduced in rats treated with resveratrol. A reduction in sterol-regulatory element binding protein 1 (SREBP1) and an increase in carnitine palmitoyltransferase 1a (CPT1a) were observed in resveratrol-treated rats. No changes were found in fatty acid synthase (FAS). In cultured hepatocytes, SREBP1 protein was increased after the transfection of each miRNA. FAS protein expression was decreased after the transfection of miRNA-122-5p, and CPT1a protein was down-regulated by the over-expression of miRNA-107-3p. This study provides new evidences which show that srebf1 is a target gene for miRNA-103-3p and miRNA-107-3p, fasn a target gene for miRNA-122-5p and cpt1a a target gene for miRNA-107-3p. Moreover, the reduction in liver steatosis induced by resveratrol in rats fed an obesegenic diet is mediated, at least in part, by the increase in CPT1a protein expression and activity, via a decrease in miRNA-107-3p expression.
本研究的目的是确定先前在我们实验室中观察到的,喂食致肥胖饮食的大鼠队列中肝脏脂肪的减少是否由微小RNA(miRNA)-103-3p、miRNA-107-3p和miRNA-122-5p的表达变化介导,这些miRNA占肝脏中总miRNA的70%,以及它们的靶基因的表达变化。在用白藜芦醇处理的大鼠中,所分析的三种miRNA的表达降低。在白藜芦醇处理的大鼠中观察到固醇调节元件结合蛋白1(SREBP1)减少,肉碱棕榈酰转移酶1a(CPT1a)增加。未发现脂肪酸合酶(FAS)有变化。在培养的肝细胞中,转染每种miRNA后SREBP1蛋白增加。转染miRNA-122-5p后FAS蛋白表达降低,miRNA-107-3p过表达使CPT1a蛋白下调。本研究提供了新的证据,表明srebf1是miRNA-103-3p和miRNA-107-3p的靶基因,fasn是miRNA-122-5p的靶基因,cpt1a是miRNA-107-3p的靶基因。此外,白藜芦醇诱导喂食致肥胖饮食的大鼠肝脏脂肪变性的减少至少部分是通过miRNA-107-3p表达的降低,导致CPT1a蛋白表达和活性增加介导的。