Cao Weina, Li Meihang, Wu Tianjiao, Feng Fei, Feng Tongying, Xu Yang, Sun Chao
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
Oncotarget. 2017 Jun 20;8(25):40872-40884. doi: 10.18632/oncotarget.16606.
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.
α-黑素细胞刺激素（αMSH）是一种重要的腺垂体多肽激素，可调节机体代谢状态。迄今为止，众所周知，下丘脑αMSH分泌紊乱与许多代谢性疾病有关，如肥胖症和II型糖尿病。然而，其潜在机制尚不清楚。在我们的研究中，我们聚焦于活性氧（ROS）诱导的脂肪细胞凋亡，并试图揭示αMSH在此过程中的作用以及αMSH作用的信号通路。我们使用昆明小白鼠，通过注射过氧化氢（H2O2）诱导其进入氧化应激状态，发现小鼠血清中αMSH显著降低，而在小鼠脂肪组织中观察到ROS水平升高和促凋亡基因的mRNA水平升高。此外，当检测αMSH在ROS诱导的凋亡中的功能时，发现其在ROS诱导的脂肪细胞凋亡中与氧化应激抑制剂N-乙酰-L-半胱氨酸（NAC）具有相似的抑制趋势，且这种趋势依赖于αMSH受体黑皮质素5受体（MC5R），而在αMSH与Foxo1之间发现了相反的趋势，Foxo1是已知的脂肪细胞凋亡的正调控因子。进一步地，我们发现αMSH对脂肪细胞凋亡的抑制作用是通过Foxo1/mTORC2信号通路发挥的。这些发现表明，αMSH对ROS诱导的脂肪细胞凋亡具有强烈的抑制作用，其潜在机制是与mTOR信号通路中的关键因子相互作用。我们的研究证明了αMSH在脂肪细胞凋亡中的重要作用，并为肥胖症和糖尿病的治疗带来了一种新的治疗手段。
