Alpha Msh Prevents Ros-Induced Apoptosis By Inhibiting Foxo1/Mtorc2 In Mice Adipose Tissue

Alpha-melanocyte stimulating hormone (alpha MSH) is an important adenohypophysis polypeptide hormone that regulates body metabolic status. To date, it is well known that the disorder of hypothalamic alpha MSH secretion is related to many metabolic diseases, such as obesity and type II diabetes. However, the underlying mechanisms are poorly understood. In our study, we focused on the reactive oxygen species (ROS)-induced adipocyte apoptosis and tried to unveil the role of alpha MSH in this process and the signal pathway which alpha MSH acts through. Kunming white mice were used and induced to oxidative stress status by hydrogen peroxide (H2O2) injection and a significant reduction of alpha MSH were found in mice serum, while elevated ROS level and mRNA level of pro-apoptotic genes were observed in mice adipose tissue. What is more, when detect the function of alpha MSH in ROS-induced apoptosis, similar inhibitory trend was found with the oxidative stress inhibitor N-acetyl-L-cysteine (NAC) in ROS-induced adipocyte apoptosis and this trend is alpha MSH receptor melanocortin 5 receptor (MC5R) depended, while an opposite trend was found between alpha MSH and Foxo1, which is a known positive regulator of adipocyte apoptosis. Further, we found that the repress effect of alpha MSH in adipocytes apoptosis is acting through Foxo1/mTORC2 pathway. These findings indicate that, alpha MSH has a strong inhibitory effect on ROS-induced adipocyte apoptosis and underlying mechanism is interacting with key factors in mTOR signal pathway. Our study demonstrated a great role of alpha MSH in adipocyte apoptosis and brings a new therapeutic mean to the treatment of obesity and diabetes.