Yu C-H, Chu S-C, Chen P-N, Hsieh Y-S, Kuo D-Y
Department of Physiology, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung City, Taiwan.
Department of Food Science, Central Taiwan University of Science and Technology, Taichung City, Taiwan.
Genes Brain Behav. 2017 Apr;16(4):439-448. doi: 10.1111/gbb.12360. Epub 2016 Dec 14.
Phenylpropanolamine (PPA)-induced appetite control is associated with oxidative stress in the hypothalamus. This study explored whether hypothalamic antioxidants participated in hypothalamic ghrelin system-associated appetite control in PPA-treated rats. Rats were given PPA daily for 4 days, and changes in food intake and the expression of neuropeptide Y (NPY), the cocaine- and amphetamine-regulated transcript (CART), superoxide dismutase, catalase, ghrelin, acyl ghrelin (AG), ghrelin O-acyltransferase (GOAT) and the ghrelin receptor (GHSR1a) were examined and compared. Results showed that both food intake and the expression of NPY and ghrelin/AG/GOAT/GHSR1a decreased in response to PPA treatment with maximum decrease on Day 2 of the treatment. In contrast, the expression of antioxidants and CART increased, with the maximum increase on Day 2, with the expression opposite to that of NPY and ghrelin. A cerebral infusion of either a GHSR1a antagonist or reactive oxygen species scavenger modulated feeding behavior and NPY, CART, antioxidants and ghrelin system expression, showing the involvement of ghrelin signaling and oxidative stress in regulating PPA-mediated appetite control. We suggest that hypothalamic ghrelin signaling system, with the help of antioxidants, may participate in NPY/CART-mediated appetite control in PPA-treated rats.
苯丙醇胺（PPA）诱导的食欲控制与下丘脑的氧化应激有关。本研究探讨下丘脑抗氧化剂是否参与PPA处理大鼠下丘脑胃饥饿素系统相关的食欲控制。大鼠连续4天每日给予PPA，并检测和比较食物摄入量以及神经肽Y（NPY）、可卡因和苯丙胺调节转录物（CART）、超氧化物歧化酶、过氧化氢酶、胃饥饿素、酰基胃饥饿素（AG）、胃饥饿素O-酰基转移酶（GOAT）和胃饥饿素受体（GHSR1a）的表达变化。结果显示，PPA处理后食物摄入量以及NPY和胃饥饿素/AG/GOAT/GHSR1a的表达均下降，在处理第2天下降幅度最大。相反，抗氧化剂和CART的表达增加，在第2天增加幅度最大，其表达与NPY和胃饥饿素相反。向脑内注入GHSR1a拮抗剂或活性氧清除剂可调节摄食行为以及NPY、CART、抗氧化剂和胃饥饿素系统的表达，表明胃饥饿素信号传导和氧化应激参与调节PPA介导的食欲控制。我们认为，下丘脑胃饥饿素信号系统在抗氧化剂的帮助下，可能参与PPA处理大鼠中NPY/CART介导的食欲控制。
