Open AccessmiR‐212 downregulation contributes to the protective effect of exercise against non‐alcoholic fatty liver via targeting FGF ‐21
Author(s) -
Xiao Junjie,
Bei Yihua,
Liu Jingqi,
DimitrovaShumkovska Jasmina,
Kuang Dapeng,
Zhou Qiulian,
Li Jin,
Yang Yanning,
Xiang Yang,
Wang Fei,
Yang Changqing,
Yang Wenzhuo
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12733
Subject(s) - lipogenesis , fgf21 , fatty liver , downregulation and upregulation , endocrinology , medicine , steatosis , beta oxidation , lipid metabolism , chemistry , fibroblast growth factor , metabolism , biochemistry , disease , gene , receptor
Non‐alcoholic fatty liver disease ( NAFLD ) is associated with obesity and lifestyle, while exercise is beneficial for NAFLD . Dysregulated micro RNA s (miRs) control the pathogenesis of NAFLD . However, whether exercise could prevent NAFLD via targeting micro RNA is unknown. In this study, normal or high‐fat diet ( HF ) mice were either subjected to a 16‐week running program or kept sedentary. Exercise attenuated liver steatosis in HF mice. Micro RNA array and qRT ‐ PCR demonstrated that miR‐212 was overexpressed in HF liver, while reduced by exercise. Next, we investigated the role of miR‐212 in lipogenesis using HepG2 cells with/without long‐chain fatty acid treatment (± FFA ). FFA increased miR‐212 in HepG2 cells. Moreover, miR‐212 promoted lipogenesis in HepG2 cells (± FFA ). Fibroblast growth factor ( FGF )‐21, a key regulator for lipid metabolism, was negatively regulated by miR‐212 at protein level in HepG2 cells. Meanwhile, FFA downregulated FGF ‐21 both at mRNA and protein levels in HepG2 cells. Also, FGF ‐21 protein level was reduced in HF liver, while reversed by exercise in vivo . Furthermore, si RNA ‐ FGF ‐21 abolished the lipogenesis‐reducing effect of miR‐212 inhibitor in HepG2 cells (± FFA ), validating FGF ‐21 as a target gene of miR‐212. These data link the benefit of exercise and miR‐212 downregulation in preventing NAFLD via targeting FGF ‐21.