title: Overexpression of human adiponectin in transgenic mice results in suppression of fat accumulation and prevention of premature death by high-calorie diet.
abstract: Adiponectin, a physiologically active polypeptide secreted by adipocytes, shows insulin-sensitizing, anti-inflammatory, and antiatherogenic properties in rodents and humans. To assess the effects of chronic hyperadiponectinemia on metabolic phenotypes, we established three lines of transgenic mice expressing human adiponectin in the liver. When maintained on a high-fat/high-sucrose diet, mice of two lines that had persistent hyperadiponectinemia exhibited significantly decreased weight gain associated with less fat accumulation and smaller adipocytes in both visceral and subcutaneous adipose tissues. Macrophage infiltration in adipose tissue was markedly suppressed in the transgenic mice. Expression levels of adiponectin receptors were not altered in skeletal muscle or liver. Circulating levels of endogenous adiponectin were elevated, whereas fasting glucose, insulin, and leptin levels were reduced compared with control mice. In the hyperadiponectinemic mice daily food intake was not altered, but oxygen consumption was significantly greater, suggesting increased energy expenditure. Moreover, high-calorie diet-induced premature death was almost completely prevented in the hyperadiponectinemic mice in association with attenuated oxidative DNA damage. The transgenic mice also showed longer life span on a conventional low-fat chow. In conclusion, transgenic expression of human adiponectin blocked the excessive fat accumulation and reduced the morbidity and mortality in mice fed a high-calorie diet. These observations may provide new insights into the prevention and therapy of metabolic syndrome in humans.
authors: Department of Medicine, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan.
authors: Shuichi
authors: S
authors: Otabe
authors: Xiaohong
authors: X
authors: Yuan
authors: Tomoka
authors: T
authors: Fukutani
authors: Nobuhiko
authors: N
authors: Wada
authors: Toshihiko
authors: T
authors: Hashinaga
authors: Hitomi
authors: H
authors: Nakayama
authors: Naotoshi
authors: N
authors: Hirota
authors: Masayasu
authors: M
authors: Kojima
authors: Kentaro
authors: K
authors: Yamada
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D052438:Adipocytes, White / Q000166:cytology; D052242:Adiponectin / Q000097:blood / Q000235:genetics; D000273:Adipose Tissue / Q000254:growth & development*; D000818:Animals; D050218:Body Fat Distribution; D001835:Body Weight; D002634:Chemotaxis, Leukocyte; D003643:Death; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D004036:Diet, Atherogenic; D004435:Eating / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008136:Longevity / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009929:Organ Size / Q000235:genetics; D010101:Oxygen Consumption / Q000235:genetics
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine