title: Hepatocyte Growth Factor Prevented High-Fat Diet-Induced Obesity and Improved Insulin Resistance in Mice.
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.
authors.affiliation: Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.|Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Muratsu
authors.affiliation: Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Iwabayashi
authors.affiliation: Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
authors.forename: Fumihiro
authors.identifier: 0000-0002-3728-5607
authors.initials: F
authors.lastname: Sanada
authors.affiliation: Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan. taniyama@cgt.med.osaka-u.ac.jp.|Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan. taniyama@cgt.med.osaka-u.ac.jp.
authors.forename: Yoshiaki
authors.identifier: 0000-0002-6057-7982
authors.initials: Y
authors.lastname: Taniyama
authors.affiliation: Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
authors.forename: Rei
authors.initials: R
authors.lastname: Otsu
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
authors.forename: Hiromi
authors.identifier: 0000-0001-6508-4338
authors.initials: H
authors.lastname: Rakugi
authors.affiliation: Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan. morishit@cgt.med.osaka-u.ac.jp.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Morishita
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose; D001835:Body Weight; D059305:Diet, High-Fat; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; C066855:HGF protein, human; D018836:Inflammation Mediators; D007328:Insulin; D017228:Hepatocyte Growth Factor