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Role of bone morphogenetic protein‐9 in the regulation of glucose and lipid metabolism
Author(s) -
Yang Min,
Liang Zerong,
Yang Mengliu,
Jia Yanjun,
Yang Gangyi,
He Yirui,
Li Xinrun,
Gu Harvest F.,
Zheng Hongting,
Zhu Zhiming,
Li And Ling
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201802544rr
Subject(s) - sterol regulatory element binding protein , lipid metabolism , endocrinology , medicine , carbohydrate metabolism , bone morphogenetic protein , chemistry , insulin resistance , biology , insulin , biochemistry , sterol , gene , cholesterol
Bone morphogenetic protein ( BMP )‐9 has been reported to regulate energy balance in vivo . However, the mechanisms underlying BMP9 ‐mediated regulation of energy balance remain incompletely understood. Here, we investigated the role of BMP9 in energy metabolism. In the current study, we found that hepatic BMP9 expression 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 hepatic BMP9 improved 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, BMP9 overexpression 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 of BMP9 were ablated. Mechanistically, BMP9 inhibited SREBP‐1c expression through the inhibition of liver X receptor response element 1 activity in the SREBP‐1c promoter. Taken together, our results show that BMP9 is 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