Possible involvement of uncoupling protein 1 in appetite control by leptin
Possible involvement of uncoupling protein 1 in appetite control by leptin
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DOI：
10.1258/ebm.2011.011143
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发表时间：
2011-11-01
影响因子：
3.2
通讯作者：
Saito, Masayuki
中科院分区：
文献类型：
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作者：
Okamatsu-Ogura, Yuko;Nio-Kobayashi, Junko;Saito, Masayuki
瘦素通过减少食物摄入和增加能量消耗来减少体内脂肪。据报道，解偶联蛋白 (UCP) 1 是棕色脂肪组织 (BAT) 产热的关键分子，有助于瘦素对能量消耗的刺激作用。为了阐明 UCP1 是否也参与瘦素的厌食作用，在本研究中，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。与 UCP1-KO 小鼠相比，重复注射瘦素在 WT 小鼠中更显着地减少食物摄入量，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 和白色脂肪组织 (WAT) 中的 UCP1 表达，因此我们通过重复注射 CL316,243 (CL)（一种高度特异性的 β 3-肾上腺素受体激动剂）来模拟 UCP1 诱导，并测量单次注射瘦素后的食物摄入量。两周的 CL 治疗增强了 WT 小鼠中瘦素的食欲抑制作用，但对 UCP1-KO 小鼠没有作用。对WT小鼠进行三天的CL治疗也增强了瘦素的食欲减退作用，并且增强了瘦素诱导的下丘脑弓状核中信号转导子和转录激活子3（STAT3）的磷酸化，而肥胖没有任何显着变化。这些结果表明，UCP1 增强下丘脑水平的瘦素作用，表明 UCP1 不仅通过调节能量消耗，而且还通过调节瘦素作用来控制食欲，从而有助于控制能量平衡。
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 beta 3-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.