αMSH prevents ROS-induced apoptosis by inhibiting Foxo1/mTORC2 in mice adipose tissue.

Weina Cao,Fei Feng,Chao Sun,Yang Xu,Tianjiao Wu,Tongying Feng,Meihang Li

doi:10.18632/oncotarget.16606

Weina Cao, Fei Feng + Show 5 more

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https://doi.org/10.18632/oncotarget.16606

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Journal: Oncotarget	Publication Date: Mar 27, 2017
Citations: 19	License type: cc-by

Affiliation: North West Agriculture and Forestry University

Abstract

Alpha-melanocyte stimulating hormone (αMSH) is an important adenohypophysis polypeptide hormone that regulates body metabolic status. To date, it is well known that the disorder of hypothalamic αMSH 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 αMSH in this process and the signal pathway which αMSH acts through. Kunming white mice were used and induced to oxidative stress status by hydrogen peroxide (H2O2) injection and a significant reduction of αMSH 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 αMSH 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 αMSH receptor melanocortin 5 receptor (MC5R) depended, while an opposite trend was found between αMSH and Foxo1, which is a known positive regulator of adipocyte apoptosis. Further, we found that the repress effect of αMSH in adipocytes apoptosis is acting through Foxo1/mTORC2 pathway. These findings indicate that, αMSH 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 αMSH in adipocyte apoptosis and brings a new therapeutic mean to the treatment of obesity and diabetes.

Highlights

Alpha-melanocyte stimulating hormone is an endocrine hormone secreted by adenohypophysis
We investigated the role of Forkhead box class O 1 (Foxo1) and mTORC2 signal in the process of αMSH inhibiting adipocytes apoptosis
When melanocortin 5 receptor (MC5R) was knocked down, the inhibitory function of αMSH in oxidative stress was correspondently blocked. These results demonstrated that the suppressive function of αMSH in oxidative stress and apoptosis is through targeting MC5R in mice adipocytes

Summary

Introduction

Alpha-melanocyte stimulating hormone (αMSH) is an endocrine hormone secreted by adenohypophysis. By binding to its receptors (MCRs), αMSH mediates multiple physiological functions, including metabolic regulation [1], neuroprotection [2], anti-inflammation [3] etc. In the function of metabolic regulation, αMSH can reduce food intake and increase energy consumption in peripheral tissues and organs via its receptors in the target tissues [4,5]. When αMSH-MC5R pathway is inhibited in vivo, mice show a great increase of lipid deposition and prone to develop obesity [6]. In mice adipocytes, adding of exogenous αMSH is found to promotes preadipocyte proliferation and enhance fatty acid oxidation [5, 7]. Few literatures were found in the study of αMSH in adipocyte apoptosis and the regulatory mechanism in the process

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