Liu Xiao-Yan, Shi Jian-Hua, DU Wen-Hua, Fan Yan-Ping, Hu Xiao-Lei, Zhang Chen-Chen, Xu Huan-Bai, Miao Yan-Jun, Zhou Hai-Yan, Xiang Ping, Chen Feng-Ling
Department of Endocrinology, No. 3 People's Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai 201900;
Exp Ther Med. 2011 Sep;2(5):977-984. doi: 10.3892/etm.2011.292. Epub 2011 Jun 21.
The aim of the present study was to investigate the effects of glucocorticoids (GCs) on appetite and gene expression of the hypothalamic appetite regulatory peptides, neuropeptide Y (NPY), agouti-related protein (AGRP) and cocaine and amphetamine-regulated transcript (CART), in non-obese and obese rats. Both non-obese and obese rats were randomly assigned to three groups: normal saline, low- and high-dose GC groups (NSG, LDG and HDG, respectively), which received an intraperitoneal injection with normal saline (0.2 ml/100 g) or hydrocortisone sodium succinate at 5 and 15 mg/kg, respectively, for 20 days. The expression levels of NPY, AGRP and CART mRNA in the hypothalamus were measured by real-time quantitative PCR. Non-obese and obese rats were found to undergo weight loss after GC injection, and a higher degree of weight loss was observed in the HDG rats. The average and cumulative food intakes in the obese and non-obese rats injected with high-dose GC were lower compared to that in the NSG (p<0.05). mRNA expression levels of the orexigenic neuropeptides, NPY and AGRP, and the anorexigenic neuropeptide, CART, were significantly lower in the HDG than levels in the NSG for both the obese and non-obese rats (p<0.05). GC treatment decreased appetite and body weight, induced apparent glucolipid metabolic disturbances and hyperinsulinemia, while down-regulated mRNA expression levels of the orexigenic neuropeptides, NPY and AGRP, and anorexigenic neuropeptide, CART, in the hypothalamus in the rats. The mechanism which induces this neuropeptide expression requires further study.
本研究旨在探讨糖皮质激素（GCs）对非肥胖和肥胖大鼠食欲及下丘脑食欲调节肽、神经肽Y（NPY）、刺鼠相关蛋白（AGRP）和可卡因及苯丙胺调节转录物（CART）基因表达的影响。非肥胖和肥胖大鼠均随机分为三组：生理盐水组、低剂量GC组和高剂量GC组（分别为NSG、LDG和HDG），分别腹腔注射生理盐水（0.2 ml/100 g）或琥珀酸钠氢化可的松，剂量分别为5和15 mg/kg，持续20天。通过实时定量PCR检测下丘脑NPY、AGRP和CART mRNA的表达水平。发现非肥胖和肥胖大鼠注射GC后体重减轻，且HDG大鼠体重减轻程度更高。与NSG组相比，注射高剂量GC的肥胖和非肥胖大鼠的平均和累积食物摄入量较低（p<0.05）。对于肥胖和非肥胖大鼠，HDG组中促食欲神经肽NPY和AGRP以及抑食欲神经肽CART的mRNA表达水平均显著低于NSG组（p<0.05）。GC治疗降低了食欲和体重，导致明显的糖脂代谢紊乱和高胰岛素血症，同时下调了大鼠下丘脑中促食欲神经肽NPY和AGRP以及抑食欲神经肽CART的mRNA表达水平。诱导这种神经肽表达的机制需要进一步研究。
