Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
Exp Biol Med (Maywood). 2011 Nov;236(11):1274-81. doi: 10.1258/ebm.2011.011143. Epub 2011 Oct 10.
Leptin reduces body fat by decreasing food intake and increasing energy expenditure. Uncoupling protein (UCP) 1, a key molecule for brown adipose tissue (BAT) thermogenesis, was reported to contribute to the stimulatory effect of leptin on energy expenditure. To clarify whether UCP1 is also involved in the anorexigenic effect of leptin, in this study we examined the effect of leptin on food intake using wild-type (WT) and UCP1-deficient (UCP1-KO) mice. Repeated injection of leptin decreased food intake more markedly in WT mice than in UCP1-KO mice, while a single injection of leptin showed similar effects in the two groups of mice. As chronic leptin stimulation induces UCP1 expression in BAT and ectopically in white adipose tissue (WAT), we mimicked the UCP1 induction by repeated injection of CL316,243 (CL), a highly specific β3-adrenoceptor agonist, and measured food intake in response to a single injection of leptin. Two-week treatment with CL enhanced the anorexigenic effect of leptin in WT mice, but not in UCP1-KO mice. Three-day treatment with CL in WT mice also enhanced the anorexigenic effect of leptin and leptin-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3) in the arcuate nucleus of the hypothalamus, without any notable change in adiposity. These results indicate that UCP1 enhances leptin action at the hypothalamus level, suggesting UCP1 contributes to the control of energy balance not only through the regulation of energy expenditure but also through appetite control by modulating leptin action.
瘦素通过减少食物摄入和增加能量消耗来减少体脂肪。解偶联蛋白 1（UCP1）是棕色脂肪组织（BAT）产热的关键分子，据报道它有助于瘦素对能量消耗的刺激作用。为了阐明 UCP1 是否也参与了瘦素的厌食作用，在这项研究中，我们使用野生型（WT）和 UCP1 缺陷型（UCP1-KO）小鼠检查了瘦素对食物摄入的影响。瘦素的重复注射在 WT 小鼠中比在 UCP1-KO 小鼠中更显著地减少了食物摄入，而单次注射瘦素在两组小鼠中显示出相似的效果。由于慢性瘦素刺激会诱导 BAT 和异位白色脂肪组织（WAT）中 UCP1 的表达，我们模拟了重复注射 CL316,243（CL）的 UCP1 诱导作用，CL 是一种高度特异性的β3-肾上腺素能受体激动剂，并测量了对单次注射瘦素的食物摄入。用 CL 治疗两周增强了 WT 小鼠中瘦素的厌食作用，但对 UCP1-KO 小鼠没有作用。WT 小鼠用 CL 治疗三天也增强了瘦素的厌食作用，并增强了瘦素诱导的 STAT3 在弓状核中的磷酸化，而脂肪量没有明显变化。这些结果表明 UCP1 增强了下丘脑水平的瘦素作用，表明 UCP1 通过调节能量消耗和通过调节瘦素作用来控制食欲来参与能量平衡的控制。
