title: MAPK1/3 regulate hepatic lipid metabolism via ATG7-dependent autophagy.
abstract: Although many biological functions of MAPK1/ERK2-MAPK3/ERK1 (mitogen-activated protein kinase 1/3) have been reported, a direct effect of MAPK1/3 on hepatic lipid metabolism remains largely unknown. We recently showed that activation of MAPK1/3 ameliorates liver steatosis in LEPR (leptin receptor)-deficient (db/db) mice, a classic animal model for liver steatosis. Consistent with these results, knockdown of MAPK1/3 promotes liver steatosis in C57/B6J wild-type (WT) mice. Autophagic flux and ATG7 (autophagy related 7) levels are increased by MAPK1/3 activation or decreased by MAPK1/3 knockdown in livers and primary hepatocytes. Blockade of autophagic flux by chloroquine (CQ) or ATG7 knockdown reverses the ameliorated liver steatosis in MAPK1/3-activated db/db mice. Together, these findings identify a beneficial role for MAPK1/3 in liver steatosis that is mediated by ATG7-dependent autophagy, which provides novel insights into the mechanisms underlying liver steatosis and create a rationale for targeting MAPK1/3 in the treatment of liver steatosis.
authors.affiliation: a Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, the Graduate School of the Chinese Academy of Sciences , Shanghai , China.
authors.forename: Yuzhong
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: a Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, the Graduate School of the Chinese Academy of Sciences , Shanghai , China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: a Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, the Graduate School of the Chinese Academy of Sciences , Shanghai , China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Yu
authors.affiliation: a Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, the Graduate School of the Chinese Academy of Sciences , Shanghai , China.
authors.forename: Zilong
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: a Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, the Graduate School of the Chinese Academy of Sciences , Shanghai , China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xiao
authors.affiliation: a Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, the Graduate School of the Chinese Academy of Sciences , Shanghai , China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Xia
authors.affiliation: a Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, the Graduate School of the Chinese Academy of Sciences , Shanghai , China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Wang
authors.affiliation: a Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, the Graduate School of the Chinese Academy of Sciences , Shanghai , China.
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.affiliation: a Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, the Graduate School of the Chinese Academy of Sciences , Shanghai , China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Deng
authors.affiliation: a Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, the Graduate School of the Chinese Academy of Sciences , Shanghai , China.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Guo
authors.affiliation: a Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, the Graduate School of the Chinese Academy of Sciences , Shanghai , China.
authors.forename: Shanghai
authors.initials: S
authors.lastname: Chen
authors.affiliation: a Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, the Graduate School of the Chinese Academy of Sciences , Shanghai , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: a Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, the Graduate School of the Chinese Academy of Sciences , Shanghai , China.
authors.forename: Feifan
authors.initials: F
authors.lastname: Guo
mesh_terms: D000818:Animals; D001343:Autophagy; D000071193:Autophagy-Related Protein 7 / Q000378:metabolism*; D050356:Lipid Metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*
chemical_list: C502661:Atg7 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000071193:Autophagy-Related Protein 7
keywords: ATG7; ERK1/2; autophagy; lipid metabolism; β-oxidation