期刊
PHARMACOLOGY RESEARCH & PERSPECTIVES
卷 9, 期 2, 页码 -出版社
JOHN WILEY & SONS LTD
DOI: 10.1002/prp2.732
关键词
adipocyte; everolimus; glucose intolerance; insulin sensitivity; obesity
资金
- Ministry of Education, Executive Yuan [109D1-100A-A-A2]
- Show Chwan Memorial Hospital [SRD108025]
- Chang Gung Memorial Hospital [CMRPG5J0191]
- National Chung-Hsing University [TCVGH-NCHU-1097612]
- National Chiayi University [108A3-129, 108A3-147, 108A3-161]
- Taichung Veterans General Hospital
The study found that continual everolimus treatment reduced body weight gain, adipocyte size, fat pad weight, triglyceride levels, fatty liver scores, and glucose tolerance test values in mice with obesity, despite increased food consumption. However, the mice also exhibited decreased insulin sensitivity index, muscle Akt phosphorylation, GLUT4 expression, and impaired glucose tolerance, indicating potential risk of diabetes with glucose intolerance and insulin resistance.
Everolimus, which inhibits mTOR kinase activity and is clinically used in graft rejection treatment, may have a two-sided influence on metabolic syndrome; its role in obesity and hyperglycemic in animals and humans, however, has been explored insufficiently. This study further determined how continual everolimus treatment affects glucose homeostasis and body weight control in C57BL6/J mice with obesity. An obesity mouse model was developed by administering a high-fat diet (HFD) to C57BL6/J mice over 12 weeks. The experimental group, while continuing their HFD consumption, were administered everolimus daily for 8 weeks. Metabolic parameters, glucose tolerance, fatty liver score, endocrine profile, insulin sensitivity index (ISI), insulin resistance (IR) index, and Akt phosphorylation, GLUT4, TNF-alpha, and IL-1 levels were measured in vivo. Compared with the control group, the everolimus group gained less body weight and had smaller adipocytes and lower fat pad weight; triglyceride (serum and hepatic), patatin-like phospholipase domain-containing 3, and fatty acid synthase levels; fatty liver scores; and glucose tolerance test values-all despite consuming more food. However, the everolimus group exhibited decreased ISI and muscle Akt phosphorylation and GLUT4 expression as well as impaired glucose tolerance and serum TNF-alpha and IL-1 beta levels-even when insulin levels were high. In conclusion, continual everolimus treatment may lead to diabetes with glucose intolerance and IR.
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