Bone morphogenetic protein 4 (BMP4) promotes hepatic glycogen accumulation and reduces glucose level in hepatocytes through mTORC2 signaling pathway

Liqin An; Qiong Shi; Ying Zhu; Hao Wang; Qi Peng; Jinghong Wu; Yu Cheng; Wei Zhang; Yanyu Yi; Zihao Bao; Hui Zhang; Yetao Luo; Jiaming Fan

doi:10.1016/j.gendis.2020.11.004

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Bone morphogenetic protein 4 (BMP4) promotes hepatic glycogen accumulation and reduces glucose level in hepatocytes through mTORC2 signaling pathway

更新时间：2022-06-24

- Bone morphogenetic protein 4 (BMP4) promotes hepatic glycogen accumulation and reduces glucose level in hepatocytes through mTORC2 signaling pathway
- Genes & Diseases Vol. 8, Issue 4, (2021)
- 作者机构：
  
  1. Ministry of Education Key Laboratory of Diagnostic Medicine, Department of Clinical Biochemistry, School of Laboratory Medicine, Chongqing Medical University,Chongqing,PR China,400016
  2. Department of Clinical Laboratory, The Second Affiliated Hospital of Chongqing Medical University,Chongqing,PR China,400010
  3. Clinical Epidemiology and Biostatistics Department, Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University,Chongqing,PR China,400014
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2020.11.004
  CLC：
- Published：2021，
  
  Published Online：1 July 2021，
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Liqin An, Qiong Shi, Ying Zhu, et al. Bone morphogenetic protein 4 (BMP4) promotes hepatic glycogen accumulation and reduces glucose level in hepatocytes through mTORC2 signaling pathway. [J]. Genes & Diseases 8(4).(2021)
DOI：

Liqin An, Qiong Shi, Ying Zhu, et al. Bone morphogenetic protein 4 (BMP4) promotes hepatic glycogen accumulation and reduces glucose level in hepatocytes through mTORC2 signaling pathway. [J]. Genes & Diseases 8(4).(2021) DOI： 10.1016/j.gendis.2020.11.004.

摘要

Abstract

Liver is an important organ for regulating glucose and lipid metabolism. Recent studies have shown that bone morphogenetic proteins (BMPs) may play important roles in regulating glucose and lipid metabolism. In our previous studies

we demonstrated that BMP4 significantly inhibits hepatic steatosis and lowers serum triglycerides

playing a protective role against the progression of non-alcoholic fatty liver disease (NAFLD). However

the direct impact of BMP4 on hepatic glucose metabolism is poorly understood. Here

we investigated the regulatory roles of BMP4 in hepatic glucose metabolism. Through a comprehensive analysis of the 14 types of BMPs

we found that BMP4 was one of the most potent BMPs in promoting hepatic glycogen accumulation

reducing the level of glucose in hepatocytes and effecting the expression of genes related to glucose metabolism. Mechanistically

we demonstrated that BMP4 reduced the hepatic glucose levels through the activation of mTORC2 signaling pathway

in vitro

and

in vivo.

Collectively

our findings strongly suggest that BMP4 may play an essential role in regulating hepatic glucose metabolism. This knowledge should aid us to understand the molecular pathogenesis of NAFLD

and may lead to the development of novel therapeutics by exploiting the inhibitory effects of BMPs on hepatic glucose and lipid metabolism.

关键词

Keywords

BMP4Glucose metabolismGlycogen accumulationmTORC2 signalingNon-alcoholic fatty liver disease (NAFLD)

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