Small C J, Kim M S, Stanley S A, Mitchell J R, Murphy K, Morgan D G, Ghatei M A, Bloom S R
Department of Metabolic Medicine, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
Diabetes. 2001 Feb;50(2):248-54. doi: 10.2337/diabetes.50.2.248.
The melanocortin receptor (MC3-R and MC4-R) antagonist, agouti-related protein (AGRP), is a potent stimulant of food intake. We examined the effect of chronic intracerebroventricular (ICV) AGRP treatment on energy metabolism and pituitary function in ad libitum fed rats and rats administered AGRP and then pair-fed to a saline control group. Chronic ICV AGRP (83-132) administration (1 nmol/day for 7 days) significantly increased food intake and body weight in ad libitum fed animals compared with saline-treated controls (body weight on day 7: 272 +/- 6 [saline] vs. 319 +/- 8 g [AGRP ad libitum fed]; P < 0.001). A significant increase in the epididymal fat pad weight, interscapular brown adipose tissue (BAT) weight, and plasma leptin was also observed in the ad libitum fed group. In the AGRP pair-fed group, a significant increase in the epididymal fat pad weight, BAT weight, and plasma leptin was again observed, suggesting that AGRP caused metabolic changes independent of increased food intake. BAT uncoupling protein 1 (UCP-1) content was significantly decreased compared with saline controls in both the AGRP ad libitum fed (21 +/- 8% of saline control; P < 0.01) and AGRP pair-fed groups (24 +/- 7% of saline control; P < 0.01). Plasma thyroid-stimulating hormone (TSH) was significantly suppressed compared with saline controls in both the AGRP ad libitum fed and AGRP pair-fed groups (3.5 +/- 0.3 [saline] vs. 2.7 +/- 0.4 [AGRP ad libitum fed] vs. 2.1 +/- 0.2 ng/ml [AGRP pair-fed]; P < 0.01). This study demonstrates that independent of its orexigenic effects, chronic AGRP treatment decreased BAT UCP-1, suppressed plasma TSH, and increased fat mass and plasma leptin, suggesting that it may play a role in energy expenditure.
黑皮质素受体（MC3-R和MC4-R）拮抗剂刺鼠相关蛋白（AGRP）是一种强效的食物摄入刺激物。我们研究了慢性脑室内（ICV）注射AGRP对自由进食大鼠以及注射AGRP后与生理盐水对照组配对喂养的大鼠能量代谢和垂体功能的影响。与生理盐水处理的对照组相比，慢性ICV注射AGRP（83-132）（1 nmol/天，共7天）显著增加了自由进食动物的食物摄入量和体重（第7天体重：生理盐水组为272±6克，自由进食AGRP组为319±8克；P<0.001）。在自由进食组中，还观察到附睾脂肪垫重量、肩胛间棕色脂肪组织（BAT）重量和血浆瘦素显著增加。在AGRP配对喂养组中，再次观察到附睾脂肪垫重量、BAT重量和血浆瘦素显著增加，这表明AGRP引起的代谢变化与食物摄入量增加无关。与生理盐水对照组相比，AGRP自由进食组（为生理盐水对照组的21±8%；P<0.01）和AGRP配对喂养组（为生理盐水对照组的24±7%；P<0.01）的BAT解偶联蛋白1（UCP-1）含量均显著降低。与生理盐水对照组相比，AGRP自由进食组和AGRP配对喂养组的血浆促甲状腺激素（TSH）均显著受到抑制（生理盐水组为3.5±0.3，自由进食AGRP组为2.7±0.4，配对喂养AGRP组为2.1±0.
