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Insulin‐like growth factor binding protein 7 accelerates hepatic steatosis and insulin resistance in non‐alcoholic fatty liver disease
Author(s) -
Yan Hua,
Li Ting,
Wang Yatao,
Li Hong,
Xu Jingyuan,
Lu Xiaolan
Publication year - 2019
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.13159
Subject(s) - insulin resistance , medicine , endocrinology , steatosis , fatty liver , lipogenesis , downregulation and upregulation , insulin , protein kinase b , carbohydrate responsive element binding protein , hepatocyte , biology , lipid metabolism , apoptosis , disease , in vitro , biochemistry , transcription factor , gene
An association between increased insulin‐like growth factor binding protein‐7 ( IGFBP 7) expression and insulin resistance in metabolic diseases has been reported. However, the role and molecular mechanism of IGFBP ‐7 in non‐alcoholic fatty liver disease ( NAFLD ) remains largely unknown. Therefore, the potential function of IGFBP 7 in the pathological progression of NAFLD was explored in this investigation. For in vivo experiments, an animal model of NAFLD was established in C57 BL /6 mice by feeding a high‐fat diet ( HFD ), and IGFBP 7 was knocked down by injecting adeno‐associated adenovirus ( AAV )‐mediated short‐hairpin (sh)‐ IGFBP 7 into the liver. We found that AAV ‐sh‐ IGFBP 7 treatment significantly alleviated hepatocyte injury and inhibited hepatic lipid accumulation by reducing lipogenesis‐associated gene expression. Furthermore, downregulation of IGFBP 7 markedly ameliorated IR and restored impaired insulin signalling by elevating the phosphorylation levels of IRS ‐1, Akt and GSK 3β in HFD ‐treated mice. Similar results were also confirmed by an in vitro study in a palmitic acid ( PA )‐stimulated HepG2 cell model. In conclusion, our study demonstrates that IGFBP 7 contributes to hepatic steatosis and insulin resistance in NAFLD development, which might serve as a novel therapeutic agent for the treatment of NAFLD .