Journal Article

Retinoic acid ameliorates high-fat diet-induced liver steatosis through Sirt1

Chao Geng Haifeng Xu Yinliang Zhang Yong Gao Meixia Li Xiaoyan Liu Mingyue Gao Xiaojuan Wang Xiaojun Liu Fude Fang Yongsheng Chang

2017

Overview

In this study, treatment of C57 BL/6 J(wild type, WT) mice fed a high-fat diet(HFD) with retinoic acid(RA) decreased body weight and subcutaneous and visceral fat content, reversed the apparent hepatosteatosis, and reduced hepatic intracellular triglyceride and serum alanine transaminase(ALT) and aspartate aminotransferase(AST) concentrations. Moreover, RA treatment improved glucose tolerance and insulin sensitivity in WT mice fed a HFD. However, these RA-induced effects in WT mice fed a HFD were alleviated in liver specific Sirtuin 1(Sirt1) deficient(LKO) mice fed a HFD. Furthermore,RA also could not improve glucose tolerance and insulin sensitivity in LKO mice fed a HFD. The mechanism studies indicated that RA indeed increased the expression of hepatic Sirt1 and superoxide dismutase 2(Sod2), and inhibited the expression of sterol regulatory element binding protein 1 c(Srebp-1 c) in WT mice in vivo and in vitro. RA decreased mitochondrial reactive oxygen species(ROS) production in WT primary hepatocytes and increased mitochondrial DNA(mtDNA) copy number in WT mice liver. However, these RA-mediated molecular effects were also abolished in the liver and primary hepatocytes from LKO mice. In summary, RA protected against HFD-induced hepato steatosis by decreasing Srebp-1 c expression and improving antioxidant capacity through a Sirtl-mediated mechanism.

• Publisher: Science China Press,Springer Nature B.V
• Subject: Alanine / Alanine transaminase / Antioxidants / Aspartate aminotransferase / Biomedical and Life Sciences / Body weight / Copy number / Fatty liver / Glucose tolerance / Hepatocytes / High fat diet / Insulin / Life Sciences / Liver / Mitochondrial DNA / Oxidative stress / Reactive oxygen species / Research Paper / Retinoic acid / Rodents / SIRT1 protein / Steatosis / Sterol regulatory element-binding protein / Superoxide dismutase / Transaminase