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National Chung Hsing University Institutional Repository - NCHUIR > 獸醫學院 > 獸醫學院 > 依資料類型分類 > 期刊論文 >  Long-term Administration of Rapamycin Reduces Adiposity, but Impairs Glucose Tolerance in High-Fat Diet-fed KK/HlJ Mice

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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.;Wu, Y.Y.;Chiu, Y.S.;Chen, W.Y.;Liao, J.W.;Hsu, H.M.;Chao, T.H.;Hung, S.W.;Mao, F.C.
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
日期: 2009
Issue Date: 2012-12-14 12:05:35 (UTC+8)
關連: 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.
Relation: Basic & Clinical Pharmacology & Toxicology
Appears in Collections:[依教師分類] 許恒銘
[依資料類型分類] 期刊論文
[依教師分類] 毛嘉洪
[依教師分類] 廖俊旺

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