Uehara Y, Shimizu H, Ohtani K, Sato N, Mori M
First Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
Diabetes. 1998 Jun;47(6):890-3. doi: 10.2337/diabetes.47.6.890.
Leptin, ob gene product, inhibits feeding behavior and stimulates energy expenditure in rodents. Corticotropin-releasing hormone (CRH) and neuropeptide Y (NPY), which act in the hypothalamus to influence energy homeostasis, may mediate the anorexic effect of leptin. The present studies were undertaken to examine the possible involvement of hypothalamic CRH in the anorexigenic action of leptin in male Wistar rats. Recombinant leptin (2 microg/rat), microinjected into the third ventricle, inhibited food intake at 2 h by 33.3% (P < 0.01) in rats that were deprived of food for 18 h. The intracerebroventricular injection of 2 microg leptin also increased hypothalamic CRH content (P < 0.05) at 2 h after its administration. Simultaneous intracerebroventricular administration of 5 microg/rat alpha-helical CRH 9-41 (alpha-hCRH), a CRH antagonist, with 2 microg/rat leptin attenuated the anorexic effect of leptin by 2 h. In contrast, single intracerebroventricular injection of alpha-hCRH did not affect food consumption in food-deprived rats. These results implicate hypothalamic CRH as an important mediator of the anorexic effect of leptin in food-deprived rats.
瘦素是肥胖基因的产物，可抑制啮齿动物的摄食行为并刺激能量消耗。促肾上腺皮质激素释放激素（CRH）和神经肽Y（NPY）在下丘脑中发挥作用以影响能量平衡，它们可能介导了瘦素的厌食作用。本研究旨在探讨下丘脑CRH在雄性Wistar大鼠中瘦素的厌食作用中可能发挥的作用。给禁食18小时的大鼠第三脑室内微量注射重组瘦素（2微克/只），2小时时食物摄入量减少33.3%（P<0.01）。脑室内注射2微克瘦素后2小时，下丘脑CRH含量也增加（P<0.05）。脑室内同时给予5微克/只的CRH拮抗剂α-螺旋CRH 9-41（α-hCRH）和2微克/只瘦素，2小时时瘦素的厌食作用减弱。相比之下，脑室内单次注射α-hCRH对禁食大鼠的食物消耗没有影响。这些结果表明，下丘脑CRH是瘦素在禁食大鼠中厌食作用的重要介导物。
