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Research Article | Open Access

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

Liqin Ana,1, Qiong Shia,1, Ying Zhua, Hao Wanga, Qi Penga, Jinghong Wua, Yu Chengb, Wei Zhanga, Yanyu Yia, Zihao Baoa, Hui Zhanga, Yetao Luoc, Jiaming Fana( )
Ministry of Education Key Laboratory of Diagnostic Medicine, Department of Clinical Biochemistry, School of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, PR China
Department of Clinical Laboratory, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, PR China
Clinical Epidemiology and Biostatistics Department, Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, 400014, PR China

1 Contributed equally.]]>

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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.

Keywords

Glucose metabolismNon-alcoholic fatty liver disease (NAFLD)BMP4Glycogen accumulationmTORC2 signaling

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Genes & Diseases
Volume 8 Issue 4,
July 2021
Pages 531-544
DOI: 10.1016/j.gendis.2020.11.004
Cite this article:
An L, Shi Q, Zhu Y, et al. Bone morphogenetic protein 4 (BMP4) promotes hepatic glycogen accumulation and reduces glucose level in hepatocytes through mTORC2 signaling pathway. Genes & Diseases, 2021, 8(4): 531-544. https://doi.org/10.1016/j.gendis.2020.11.004

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Received: 24 August 2020
Revised: 14 October 2020
Accepted: 05 November 2020
Published: 13 November 2020
© 2020, Chongqing Medical University.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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