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

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

作者地址："[An, Liqin; Shi, Qiong; Zhu, Ying; Wang, Hao; Peng, Qi; Wu, Jinghong; Zhang, Wei; Yi, Yanyu; Bao, Zihao; Zhang, Hui; Fan, Jiaming] Chongqing Med Univ, Sch Lab Med, Dept Clin Biochem, Minist Educ,Key Lab Diagnost Med, 1 Med Sch Rd, Chongqing 400016, Peoples R China; [Cheng, Yu] Chongqing Med Univ, Dept Clin Lab, Affiliated Hosp 2, Chongqing 400010, Peoples R China; [Luo, Yetao] Chongqing Med Univ, Dept Pediat Res Inst, Clin Epidemiol & Biostat Dept, Childrens Hosp, Chongqing 400014, Peoples R China"

通信作者："Fan, JM (corresponding author), Chongqing Med Univ, Sch Lab Med, Dept Clin Biochem, Minist Educ,Key Lab Diagnost Med, 1 Med Sch Rd, Chongqing 400016, Peoples R China."

来源：GENES & DISEASES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000661449300013

JCR分区：Q1

影响因子：6.8

年份：2021

卷号：8

期号：4

开始页：531

结束页：544

文献类型：Review

关键词：BMP4; Glucose metabolism; Glycogen accumulation; mTORC2 signaling; Non-alcoholic fatty liver disease (NAFLD)

摘要："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. Copyright (C) 2020, Chongqing Medical University. Production and hosting by Elsevier B.V."

基金机构："2017 Chongqing Postdoctoral Innovation Talent Support Program (Chongqing Human Resources and Social Security Bureau) [356]; 64th China Postdoctoral Science Fund [2018M643426]; 2019 Chongqing Support Program for Entrepreneurship and Innovation (Chongqing Human Resources and Social Security Bureau) [288]; 2019 Science and Technology Research Plan Project of Chongqing Education Commission [KJQN201900410]; 2019 Youth Innovative Talent Training Program of Chongqing Education Commission [CY200409]; 2019 Funding for Postdoctoral Research (Chongqing Human Resources and Social Security Bureau) [298]; National Key Research and Development Program of China [2016YFC1000803, 2011CB707906]"

基金资助正文："The reported study was supported in part by research grants from the 2017 Chongqing Postdoctoral Innovation Talent Support Program (Chongqing Human Resources and Social Security Bureau No. 356) (JMF), the 64th China Postdoctoral Science Fund (No. 2018M643426) (JMF), the 2019 Chongqing Support Program for Entrepreneurship and Innovation (Chongqing Human Resources and Social Security Bureau No. 288) (JMF), the 2019 Science and Technology Research Plan Project of Chongqing Education Commission (KJQN201900410) (JMF), the 2019 Youth Innovative Talent Training Program of Chongqing Education Commission (CY200409) (JMF), the 2019 Funding for Postdoctoral Research (Chongqing Human Resources and Social Security Bureau No. 298) (JMF), and the National Key Research and Development Program of China (2016YFC1000803 and 2011CB707906). Funding sources were not involved in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication."