Long-term Administration of Rapamycin Reduces Adiposity, but Impairs Glucose Tolerance in High-Fat Diet-fed KK/HlJ Mice. Basic & clinical pharmacology & toxicology [Basic Clin Pharmacol Toxicol] Journal article | | Title | Long-term Administration of Rapamycin Reduces Adiposity, but Impairs Glucose Tolerance in High-Fat Diet-fed KK/HlJ Mice. | | Author(s) | Chang GR, Wu YY, Chiu YS, Chen WY, Liao JW, Hsu HM, Chao TH, Hung SW, Mao FC | | Institution | Department of Veterinary Medicine, National Chung Hsing University, Taiwan. | | Source | Basic Clin Pharmacol Toxicol 2009 May 26. | | Abstract | 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19496779 |
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