Cyclosporin A attenuates weight gain and improves glucose tolerance in diet-induced obese mice

Abstract

Inflammation is a main factor responsible for obesity induced insulin resistance and type 2 diabetes. Since immunosuppressant activity is closely related with low level of inflammation, we predict that Cyclosporin A (CsA), an immunosuppressant drug, might have a protective role for combating inflammation-associated disorders such as obesity and type 2 diabetes. To address this issue, obese or lean mice were received CsA via gavage at the dose of 10mg/kg/day for 3weeks. Our results show that CsA treatment remarkably attenuates food intake and body weight gain in the obese mice. CsA treatment down-regulates expression of gluconeogenic gene including Pepck, G6Pase and Pgc1α, leading to a decrease in blood glucose level and an improvement of glucose tolerance in the obese animals. RT-PCR analysis of genes involved in adipocyte differentiation and lipid metabolism in white adipose tissue reveal that CsA application reduces expression of Pparγ, Fas and Scd 1. The productions of pro-inflammatory cytokines (IL-1β, IL-2, IL-12 and TNFα) and JNK activity were remarkably reduced in the CsA-treated obese animals. These results suggest that CsA treatment might play beneficial effects against obesity and obesity related hyperglycemia.