Leucine Deprivation Stimulates Fat Loss via Increasing CRH Expression in the Hypothalamus and Activating The Sympathetic Nervous System
Leucine Deprivation Stimulates Fat Loss via Increasing CRH Expression in the Hypothalamus and Activating The Sympathetic Nervous System
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DOI：
10.1210/me.2011-0028
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发表时间：
2011-09-01
影响因子：
--
通讯作者：
Guo, Feifan
中科院分区：
文献类型：
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作者：
Cheng, Ying;Zhang, Qian;Guo, Feifan
我们之前的研究表明，亮氨酸剥夺主要通过增加能量消耗来减少腹部脂肪量，正如白色脂肪组织（WAT）的脂肪分解增加和棕色脂肪组织（BAT）的解偶联蛋白1 （UCP1）表达增加所证明的那样。本研究的目的是探讨中枢神经系统（CNS）在这种调节中的可能参与，并阐明潜在的分子机制。为此，我们分析了野生型小鼠在脑室内给予亮氨酸或促肾上腺皮质激素释放激素抗体后，或缺失三种β -肾上腺素能受体的小鼠在维持缺乏亮氨酸的饮食7天后，WAT中与脂解相关的基因和蛋白质水平以及BAT中UCP1的表达。我们发现，在缺乏亮氨酸的小鼠中，脑室内给予亮氨酸可显著减轻腹部脂肪损失，并阻断WAT中激素敏感脂肪酶的激活和BAT中UCP1的诱导。此外，我们提供的证据表明，亮氨酸剥夺通过激活刺激性G蛋白/cAMP/蛋白激酶A/cAMP反应元件结合蛋白通路，增加下丘脑促肾上腺皮质激素释放激素的表达，从而刺激脂肪减少。最后，我们表明亮氨酸剥夺对脂肪减少的影响是通过激活交感神经系统介导的。这些结果表明，中枢神经系统在亮氨酸剥夺下的脂肪损失调节中发挥重要作用，从而为中枢神经系统亮氨酸在能量稳态调节中的重要性提供了新的重要见解。（分子内分泌学25:1624-1635,2011）
We previously showed that leucine deprivation decreases abdominal fat mass largely by increasing energy expenditure, as demonstrated by increased lipolysis in white adipose tissue (WAT) and uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT). The goal of the present study was to investigate the possible involvement of central nervous system (CNS) in this regulation and elucidate underlying molecular mechanisms. For this purpose, levels of genes and proteins related to lipolysis in WAT and UCP1 expression in BAT were analyzed in wild-type mice after intracerebroventricular administration of leucine or corticotrophin-releasing hormone antibodies, or in mice deleted for three beta-adrenergic receptors, after being maintained on a leucine-deficient diet for 7 d. Here, we show that intracerebroventricular administration of leucine significantly attenuates abdominal fat loss and blocks activation of hormone sensitive lipase in WAT and induction of UCP1 in BAT in leucine-deprived mice. Furthermore, we provide evidence that leucine deprivation stimulates fat loss by increasing expression of corticotrophin-releasing hormone in the hypothalamus via activation of stimulatory G protein/cAMP/protein kinase A/cAMP response element-binding protein pathway. Finally, we show that the effect of leucine deprivation on fat loss is mediated by activation of the sympathetic nervous system. These results suggest that CNS plays an important role in regulating fat loss under leucine deprivation and thereby provide novel and important insights concerning the importance of CNS leucine in the regulation of energy homeostasis. (Molecular Endocrinology 25: 1624-1635, 2011)