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Retinoic acid ameliorates high-fat diet-induced liver steatosis through sirt1

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Abstract

In this study, treatment of C57BL/6J (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 1c (Srebp-1c) 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 hepatosteatosis by decreasing Srebp-1c expression and improving antioxidant capacity through a Sirt1-mediated mechanism.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (31371191).

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Authors and Affiliations

  1. State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine Peking Union Medical College, Beijing, 100005, China

    Chao Geng, Yinliang Zhang, Yong Gao, Xiaoyan Liu, Mingyue Gao, Xiaojuan Wang, Xiaojun Liu, Fude Fang & Yongsheng Chang

  2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Interventional Therapy, Peking University Cancer Hospital & Institute, Beijing, 100142, China

    Haifeng Xu

  3. State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China

    Meixia Li

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  1. Chao Geng
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Correspondence to Xiaojun Liu, Fude Fang or Yongsheng Chang.

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Geng, C., Xu, H., Zhang, Y. et al. Retinoic acid ameliorates high-fat diet-induced liver steatosis through sirt1. Sci. China Life Sci. 60, 1234–1241 (2017). https://doi.org/10.1007/s11427-016-9027-6

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  • DOI: https://doi.org/10.1007/s11427-016-9027-6

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