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 regu-lating glucose and lipid metabolism.Inour previo...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 regu-lating glucose and lipid metabolism.Inour previous studies,we demonstrated that BMP4 signif-icantly 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 lewels through the activation of mTORC2 signaling pathway in vitro and in wivo.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.展开更多
基金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)+4 种基金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)the National Key Research and Development Program of China(2016YFC1000803 and 2011CB707906).
文摘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 regu-lating glucose and lipid metabolism.Inour previous studies,we demonstrated that BMP4 signif-icantly 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 lewels through the activation of mTORC2 signaling pathway in vitro and in wivo.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.
