Role of bone morphogenetic protein-9 in the regulation of glucose and lipid metabolism
Role of bone morphogenetic protein-9 in the regulation of glucose and lipid metabolism
复制标题
骨形态发生蛋白9在糖脂代谢调节中的作用
DOI：
10.1096/fj.201802544rr
复制
发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Li Ling
中科院分区：
文献类型：
--
作者：
Yang Min;Liang Zerong;Yang Mengliu;Jia Yanjun;Yang Gangyi;He Yirui;Li Xinrun;Gu Harvest F;Zheng Hongting;Zhu Zhiming;Li Ling
据报道，骨形态发生蛋白 (BMP)-9 可调节体内能量平衡。然而，BMP9 介导的能量平衡调节机制仍不完全清楚。在这里，我们研究了 BMP9 在能量代谢中的作用。在当前的研究中，我们发现胰岛素抵抗（IR）小鼠和糖尿病患者的肝脏BMP9表达下调。在喂食高脂肪饮食 (HFD) 的小鼠中，肝脏 BMP9 的过度表达改善了葡萄糖耐量和 IR。在腺病毒-BMP9处理的小鼠肝脏和葡萄糖胺处理的肝细胞中，糖异生基因的表达下调，而胰岛素信号分子磷酸化水平增加。此外，BMP9 过表达改善了甘油三酯的积累，并抑制了用脂肪酸混合物处理的人肝细胞癌 HepG2 细胞以及 HFD 喂养的小鼠肝脏中脂肪生成基因的表达。在从甾醇调节元件结合蛋白 (SREBP)-1c 敲除小鼠中分离的肝细胞中，BMP9 的作用被消除。从机制上讲，BMP9通过抑制SREBP-1c启动子中的肝脏X受体反应元件1活性来抑制SREBP-1c表达。综上所述，我们的结果表明，BMP9 是肝脏糖脂代谢的重要调节因子。—Yang, M.、Liang, Z.、Yang, M.、Jia, Y.、Yang, G.、He, Y.、Li, X.、Gu, H. F.、Zheng, H.、Zhu, Z.、Li, L. 骨形态发生蛋白-9 在糖脂代谢调节中的作用。 FASEB J. 33, 10077–10088 (2019)。 www.fasebj.org
Bone morphogenetic protein (BMP)‐9 has been reported to regulate energy balancein vivo. However, the mechanisms underlyingBMP9‐mediated regulation of energy balance remain incompletely understood. Here, we investigated the role ofBMP9in energy metabolism. In the current study, we found that hepaticBMP9expression was down‐regulated in insulin resistance (IR) mice and in patients who are diabetic. In mice fed a high‐fat diet (HFD), the overexpression of hepaticBMP9improved glucose tolerance and IR. The expression of gluconeogenic genes was down‐regulated, whereas the level of insulin signaling molecule phosphorylation was increased in the livers of Adenovirus‐BMP9‐treated mice and glucosamine‐treated hepatocytes. Furthermore,BMP9overexpression ameliorated triglyceride accumulation and inhibited the expression of lipogenic genes in both human hepatocellular carcinoma HepG2 cells treated with a fatty acid mixture as well as the livers of HFD‐fed mice. In hepatocytes isolated from sterol regulatory element‐binding protein (SREBP)‐1c knockout mice, the effects ofBMP9were ablated. Mechanistically,BMP9inhibitedSREBP‐1cexpression through the inhibition of liver X receptor response element 1 activity in theSREBP‐1cpromoter. Taken together, our results show thatBMP9is an important regulator of hepatic glucose and lipid metabolism.—Yang, M., Liang, Z., Yang, M., Jia, Y., Yang, G., He, Y., Li, X., Gu, H. F., Zheng, H., Zhu, Z., Li, L. Role of bone morphogenetic protein‐9 in the regulation of glucose and lipid metabolism. FASEB J. 33, 10077–10088 (2019). www.fasebj.org