title: miR-212 downregulation contributes to the protective effect of exercise against non-alcoholic fatty liver via targeting FGF-21.
abstract: Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and lifestyle, while exercise is beneficial for NAFLD. Dysregulated microRNAs (miRs) control the pathogenesis of NAFLD. However, whether exercise could prevent NAFLD via targeting microRNA 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. MicroRNA 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, siRNA-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.
authors.affiliation: Regeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai, China.|Shanghai Key Laboratory of Bio-Energy Crops, School of Life Sciences, Shanghai University, Shanghai, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Regeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai, China.|Shanghai Key Laboratory of Bio-Energy Crops, School of Life Sciences, Shanghai University, Shanghai, China.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Bei
authors.affiliation: Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Jingqi
authors.initials: J
authors.lastname: Liu
authors.affiliation: Regeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai, China.|Department of Experimental Biochemistry and Physiology, Faculty of Natural Sciences and Mathematics, University Ss Cyril and Methodius, Skopje, Republic of Macedonia.
authors.forename: Jasmina
authors.initials: J
authors.lastname: Dimitrova-Shumkovska
authors.affiliation: Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Dapeng
authors.initials: D
authors.lastname: Kuang
authors.affiliation: Regeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai, China.|Shanghai Key Laboratory of Bio-Energy Crops, School of Life Sciences, Shanghai University, Shanghai, China.
authors.forename: Qiulian
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Regeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai, China.|Shanghai Key Laboratory of Bio-Energy Crops, School of Life Sciences, Shanghai University, Shanghai, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Yanning
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and Department of Biochemistry, Nanjing University, Nanjing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Yang
authors.affiliation: Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Wenzhuo
authors.initials: W
authors.lastname: Yang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D059305:Diet, High-Fat / Q000009:adverse effects; D015536:Down-Regulation / Q000235:genetics*; D005227:Fatty Acids / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D005227:Fatty Acids; D035683:MicroRNAs; D012333:RNA, Messenger; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors
keywords: FGF-21; NAFLD; exercise; miR-212; steatosis