Huang Qingling, Timofeeva Elena, Richard Denis
Laval Hospital Research Center and Merck-Frosst/IRSC Obesity Research Chair, 2725 chemin Sainte-Foy, Québec, Canada.
J Endocrinol. 2006 Oct;191(1):179-88. doi: 10.1677/joe.1.06906.
The present study was conducted to investigate the long-term effects of subchronic elevation of central leptin levels on the expression of corticotropin-releasing factor (CRF) and its types 1 and 2 receptors in the brain of rats subjected to treadmill running-induced stress. PBS or recombinant murine leptin was infused continuously for a period of 5 days into the third ventricle of rats with the aid of osmotic minipumps at a delivery rate of 2 mug/day. On the fifth day of infusion, rats were killed under resting conditions or after a session of treadmill running, which is known to induce a stress response in rats. Leptin treatment significantly decreased food intake, body weight, white adipose tissue weight, glucose and insulin plasma contents, and blunted the treadmill running-induced elevation in plasma levels of corticosterone. Leptin infusion prevented stress-induced de novo synthesis of CRF in the paraventricular hypothalamic nucleus (PVN), which was measured using the intronic probe for CRF heteronuclear RNA. The induction of the type 1 CRF receptor (CRF(1)R) in the PVN and supraoptic nucleus in running rats was also significantly blunted by leptin. In contrast, leptin treatment strongly increased the expression of type 2 CRF receptor (CRF(2)R) in the ventromedial hypothalamic nucleus (VMH). The present results suggest that subchronic elevation of central levels of leptin blunts treadmill running-induced activation of the hypothalamic-pituitary-adrenal axis through the inhibition of activation of the CRFergic PVN neurons, and potentially enhances the anorectic CRF effects via the stimulation of expression of CRF(2)R in the VMH.
本研究旨在探讨中枢瘦素水平亚慢性升高对跑步机跑步诱导应激大鼠脑内促肾上腺皮质激素释放因子（CRF）及其1型和2型受体表达的长期影响。借助渗透微型泵以2微克/天的给药速率，将PBS或重组鼠瘦素连续5天注入大鼠第三脑室。在输注的第5天，大鼠在静息条件下或在一次跑步机跑步（已知可诱导大鼠应激反应）后处死。瘦素治疗显著降低了食物摄入量、体重、白色脂肪组织重量、血糖和胰岛素血浆含量，并减弱了跑步机跑步诱导的血浆皮质酮水平升高。瘦素输注可防止应激诱导的下丘脑室旁核（PVN）中CRF的从头合成，这是使用CRF异核RNA的内含子探针测量的。瘦素也显著减弱了跑步大鼠PVN和视上核中1型CRF受体（CRF(1)R）的诱导。相反，瘦素治疗强烈增加了腹内侧下丘脑核（VMH）中2型CRF受体（CRF(2)R）的表达。目前的结果表明，中枢瘦素水平的亚慢性升高通过抑制CRF能PVN神经元的激活，减弱了跑步机跑步诱导的下丘脑-垂体-肾上腺轴的激活，并可能通过刺激VMH中CRF(2)R的表达增强了CRF的厌食作用。
