Abstract
Obesity and its associated chronic inflammation in adipose tissue initiate insulin resistance, which is related to several pathologies including hypertension and atherosclerosis. Previous reports demonstrated that circulating hepatocyte growth factor (HGF) level was associated with obesity and type 2 diabetes. However, its precise role in obesity and related-pathology is unclear. In this experiment, cardiac-specific over-expression of human HGF in mice (HGF-Tg mice) which showed 4–5 times higher serum HGF levels than wild-type mice were used. While body weight in wild-type mice fed with high fat diet (HFD) for 14 weeks was significantly increased accompanied with insulin resistance, HGF-Tg mice prevented body weight gain and insulin resistance. The accumulation of macrophages and elevated levels of inflammatory mediators in adipose tissue were significantly inhibited in HGF-Tg mice as compared to wild-type mice. The HFD-induced obesity in wild-type mice treated with HGF-neutralizing antibody showed an exacerbated response to the glucose tolerance test. These gain-of-function and loss-of-function studies demonstrated that the elevated HGF level induced by HFD have protective role against obesity and insulin resistance.
Highlights
Obesity and its associated chronic inflammation in adipose tissue initiate insulin resistance, which is related to several pathologies including hypertension and atherosclerosis
Body weight was measured for 14 weeks in wild-type mice (WT) and hepatocyte growth factor (HGF)-Tg mice fed with normal chow diet (ND) or high fat diet (HFD)
To further clarify the role of endogenous HGF we examined the effects of HGF neutralizing antibody (HGF-Ab) on WT mice fed with HFD, since HGF is a well-known pleiotropic cytokine originally identified as a potent mitogen for hepatocytes[17]
Summary
Obesity and its associated chronic inflammation in adipose tissue initiate insulin resistance, which is related to several pathologies including hypertension and atherosclerosis. Previous reports demonstrated that circulating hepatocyte growth factor (HGF) level was associated with obesity and type 2 diabetes. Its precise role in obesity and related-pathology is unclear In this experiment, cardiac-specific over-expression of human HGF in mice (HGF-Tg mice) which showed 4–5 times higher serum HGF levels than wild-type mice were used. The HFD-induced obesity in wild-type mice treated with HGFneutralizing antibody showed an exacerbated response to the glucose tolerance test. These gain-offunction and loss-of-function studies demonstrated that the elevated HGF level induced by HFD have protective role against obesity and insulin resistance. In the present study, using HGF-Tg mice and anti-HGF neutralizing antibody (HGF-Ab), we explored the role of HGF in obese and insulin resistance induced by HFD
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