請用此 Handle URI 來引用此文件: http://hdl.handle.net/11455/71572
標題: Long-term Administration of Rapamycin Reduces Adiposity, but Impairs Glucose Tolerance in High-Fat Diet-fed KK/HlJ Mice
作者: Chang, G.R.
毛嘉洪
Wu, Y.Y.
Chiu, Y.S.
Chen, W.Y.
Liao, J.W.
Hsu, H.M.
Chao, T.H.
Hung, S.W.
Mao, F.C.
廖俊旺
關鍵字: differentiation-related protein
insulin-receptor substrate-1
dependent
diabetes-mellitus
mammalian target
oxidative stress
induced obesity
skeletal-muscle
food-intake
lipid-accumulation
c57bl/6j mice
期刊/報告no:: Basic & Clinical Pharmacology & Toxicology, Volume 105, Issue 3, Page(s) 188-198.
摘要: Rapamycin is an immunosuppressant drug used to prevent organ rejection in transplant patients. In this study, we investigated the metabolic effects of rapamycin in an obese animal model, KK/HlJ mice. Mice were treated with a daily intraperitoneal injection of rapamycin at 2 mg/kg or vehicle for 42 days on a high-fat diet. Treated mice lost body weight and adiposity, reduced weight gain and retroperitoneal and epididymal fat pads/body weight, decreased serum leptin and plasma triglyceride levels and had lower liver fat concentration. However, treated mice had higher serum insulin levels and food intake. Dissection of rapamycin-treated mice revealed a marked reduction in fatty liver scores and fat cell size in retroperitoneal and epididymal adipocytes. Moreover, Western blot analysis revealed that rapamycin treatment resulted in decreasing adipophilin expression, as a marker of lipid accumulation, and reducing phosphorylation of mTOR downstream targets S6K1 compared to control group. Unfortunately, rapamycin-treated animals showed a marked decline in glucose tolerance as judged by the 180-min. area under the curve for plasma glucose levels, paralleled by increased generation of plasma reactive oxygen species. These results suggest that continual rapamycin administration may help to prevent diet-induced obesity, while prolonged use of rapamycin may exacerbate glucose intolerance.
URI: http://hdl.handle.net/11455/71572
ISSN: 1742-7835
文章連結: http://dx.doi.org/10.1111/j.1742-7843.2009.00427.x
顯示於類別:獸醫學院

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