Oncotarget

Research Papers:

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

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

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Oncotarget. 2017; 8:40872-40884. https://doi.org/10.18632/oncotarget.16606

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Abstract

Weina Cao1,*, Meihang Li1,*, Tianjiao Wu1,*, Fei Feng1, Tongying Feng1, Yang Xu1 and Chao Sun1

1College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China

*These authors have contributed equally to this work

Correspondence to:

Chao Sun, email: sunchao2775@163.com

Keywords: αMSH, Foxo1, ROS, apoptosis, mTOR

Received: January 09, 2017     Accepted: March 02, 2017     Published: March 27, 2017

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.


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