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. 2016;12(3):592-3.
doi: 10.1080/15548627.2015.1135282. Epub 2016 Jan 13.

MAPK1/3 regulate hepatic lipid metabolism via ATG7-dependent autophagy

Yuzhong Xiao  1 , Hao Liu  1 , Junjie Yu  1 , Zilong Zhao  1 , Fei Xiao  1 , Tingting Xia  1 , Chunxia Wang  1 , Kai Li  1 , Jiali Deng  1 , Yajie Guo  1 , Shanghai Chen  1 , Yan Chen  1 , Feifan Guo  1
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MAPK1/3 regulate hepatic lipid metabolism via ATG7-dependent autophagy

Yuzhong Xiao et al. Autophagy. 2016.

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.

Keywords: ATG7; ERK1/2; autophagy; lipid metabolism; β-oxidation.

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  • doi: 10.2337/db15-1024

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