Leptin directly activates SF1 neurons in the VMH, and this action by leptin is required for normal body-weight homeostasis
Leptin directly activates SF1 neurons in the VMH, and this action by leptin is required for normal body-weight homeostasis
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DOI：
10.1016/j.neuron.2005.12.021
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发表时间：
2006-01-19
期刊：
影响因子：
16.2
通讯作者：
Lowelll, BB
中科院分区：
文献类型：
--
作者：
Dhillon, H;Zigman, JM;Lowelll, BB
瘦素是一种脂肪细胞衍生的激素，直接作用于大脑，以控制食物摄入和能量消耗。一个重要的问题是启动瘦素的抗肥胖作用的一阶神经元的身份。一个广泛的观点是，大多数（如果不是全部）瘦素的作用是由位于下丘脑弓形核中的神经元介导的。但是，瘦素受体（LEPR）也在其他部位表达，包括腹侧下丘脑（VMH）。瘦素作用在“非晋升”位点的可能作用在很大程度上被忽略了。在本研究中，我们表明瘦素会去极化并增加VMH中类固醇生成因子1（SF1）阳性神经元的发射速率。我们还通过产生缺乏SF1阳性神经元的LEPR的小鼠来表明，在该站点上的瘦素作用在减轻体重和抗饮食诱导的肥胖症方面起着重要作用。这些结果揭示了瘦素对VMH神经元作用的关键作用。
Leptin, an adipocyte-derived hormone, acts directly on the brain to control food intake and energy expenditure. An important question is the identity of first-order neurons initiating leptin's anti-obesity effects. A widely held view is that most, if not all, of leptin's effects are mediated by neurons located in the arcuate nucleus of the hypothalamus. However, leptin receptors (LEPRs) are expressed in other sites as well, including the ventromedial hypothalamus (VMH). The possible role of leptin acting in "nonarcuate" sites has largely been ignored. In the present study, we show that leptin depolarizes and increases the firing rate of steroidogenic factor-1 (SF1)-positive neurons in the VMH. We also show, by generating mice that lack LEPRs on SF1-positive neurons, that leptin action at this site plays an important role in reducing body weight and, of note, in resisting diet-induced obesity. These results reveal a critical role for leptin action on VMH neurons.