BMP7 improves insulin signal transduction in the liver via inhibition of mitogen-activated protein kinases

in Journal of Endocrinology
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  • 1 Department of Endocrinology and Metabolism, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
  • 2 Medical College, Nantong University, Nantong, Jiangsu Province, China
  • 3 Key Laboratory for Neuroregeneration of Jiangsu Province and Ministry of Education, Nantong University, Nantong, Jiangsu Province, China
  • 4 Department of Histology and Embryology, Medical College, Nantong University, Nantong, Jiangsu Province, China
  • 5 Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Diabetes Institute, Shanghai Clinical Center of Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, Shanghai, Jiangsu Province, China
  • 6 Laboratory Animal Center of Nantong University, Nantong, Jiangsu Province, China

Correspondence should be addressed to Y Gu: desette@ntu.edu.cn

*(H Ma and J Yuan contributed equally to this work)

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Bone morphogenetic protein 7 (BMP7), a member of the transforming growth factor-β (TGF-β) family, plays pivotal roles in energy expenditure. However, whether and how BMP7 regulates hepatic insulin sensitivity is still poorly understood. Here, we show that hepatic BMP7 expression is reduced in high-fat diet (HFD)-induced diabetic mice and palmitate (PA)-induced insulin-resistant HepG2 and AML12 cells. BMP7 improves insulin signaling pathway in insulin resistant hepatocytes. On the contrary, knockdown of BMP7 further impairs insulin signal transduction in PA-treated cells. Increased expression of BMP7 by adenovirus expressing BMP7 improves hyperglycemia, insulin sensitivity and insulin signal transduction. Furthermore, BMP7 inhibits mitogen-activated protein kinases (MAPKs) in both the liver of obese mice and PA-treated cells. In addition, inhibition of MAPKs recapitulates the effects of BMP7 on insulin signal transduction in cultured hepatocytes treated with PA. Activation of p38 MAPK abolishes the BMP7-mediated upregulation of insulin signal transduction both in vitro and in vivo. Together, our results show that hepatic BMP7 has a novel function in regulating insulin sensitivity through inhibition of MAPKs, thus providing new insights into treating insulin resistance-related disorders such as type 2 diabetes.

 

      Society for Endocrinology

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