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

in Journal of Endocrinology
Authors:
Hong Ma Department of Endocrinology and Metabolism, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
Medical College, Nantong University, Nantong, Jiangsu Province, China

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Jin Yuan Department of Endocrinology and Metabolism, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China

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Jinyu Ma Key Laboratory for Neuroregeneration of Jiangsu Province and Ministry of Education, Nantong University, Nantong, Jiangsu Province, China

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Jie Ding Key Laboratory for Neuroregeneration of Jiangsu Province and Ministry of Education, Nantong University, Nantong, Jiangsu Province, China

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Weiwei Lin Department of Histology and Embryology, Medical College, Nantong University, Nantong, Jiangsu Province, China

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Xinlei Wang Department of Endocrinology and Metabolism, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China

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Mingliang Zhang 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

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Yi Sun Department of Endocrinology and Metabolism, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
Medical College, Nantong University, Nantong, Jiangsu Province, China

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Runze Wu Department of Endocrinology and Metabolism, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
Medical College, Nantong University, Nantong, Jiangsu Province, China

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Chun Liu Laboratory Animal Center of Nantong University, Nantong, Jiangsu Province, China

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Cheng Sun Key Laboratory for Neuroregeneration of Jiangsu Province and Ministry of Education, Nantong University, Nantong, Jiangsu Province, China

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Yunjuan Gu Department of Endocrinology and Metabolism, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China

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

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

DOI:
https://doi.org/10.1530/JOE-18-0693
Volume/Issue:
Volume 243: Issue 2
Article Type:
Research Article
Page Range:
97–110
Online Publication Date:
Nov 2019
Copyright:
© 2019 Society for Endocrinology 2019
Restricted access
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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.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© 2019 Society for Endocrinology 2019
Page(s):
14
Article Type:
Research Article
Received Date:
25 Jul 2019
Accepted Date:
07 Aug 2019
Print Publication Date:
01 Nov 2019
Online Publication Date:
Nov 2019
Keywords:
bone morphogenetic protein 7; insulin signal transduction; obesity; insulin resistance; palmitate; MAPKs

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