High-fat feeding promotes obesity via insulin receptor/PI3K-dependent inhibition of SF-1 VMH neurons.
High-fat feeding promotes obesity via insulin receptor/PI3K-dependent inhibition of SF-1 VMH neurons.
复制标题
DOI：
10.1038/nn.2847
复制
发表时间：
2011-06-05
影响因子：
25
通讯作者：
Bruening, Jens C.
中科院分区：
文献类型：
--
作者：
Kloeckener, Tim;Hess, Simon;Belgardt, Bengt F.;Paeger, Lars;Verhagen, Linda A. W.;Husch, Andreas;Sohn, Jong-Woo;Hampel, Brigitte;Dhillon, Harveen;Zigman, Jeffrey M.;Lowell, Bradford B.;Williams, Kevin W.;Elmquist, Joel K.;Horvath, Tamas L.;Kloppenburg, Peter;Bruening, Jens C.
腹侧下丘脑（VMH）的SF-1表达神经元控制能量稳态，但是胰岛素作用在这些细胞中的作用仍然不确定。在这些细胞中，通过胰岛素受体（IR）缺乏，将这些作用消除了这些效果，限于SF-1神经元在正常的食物饮食下，体重和葡萄糖稳态在SF-1Δir-c中保持不变，它们免受饮食诱导的瘦素耐药性，体重增加，肥胖和葡萄糖耐受性受损的保护。小鼠，这种反应在SF-1ΔIR-鼠标的VMH中减弱。 PTEN导致体重增加，在正常的Chow饮食下，我们的实验在VMH神经元中揭示了HFD诱导的胰岛素依赖性PI3K激活的关键作用，以控制能量稳态。
SF-1-expressing neurons of the ventromedial hypothalamus (VMH) control energy homeostasis, but the role of insulin action in these cells remains undefined. We show that insulin activates PI3-kinase (PI3k) signaling in SF-1 neurons and reduces firing frequency in these cells via activation of KATP-channels. These effects are abrogated in mice with insulin receptor (IR) deficiency restricted to SF-1 neurons (SF-1ΔIR-mice). While body weight and glucose homeostasis remain unaltered in SF-1ΔIR-mice under normal chow diet, they exhibit protection from diet-induced leptin resistance, weight gain, adiposity and impaired glucose tolerance. High-fat feeding activates PI3k signaling in SF-1 neurons of control mice, and this response is attenuated in the VMH of SF-1ΔIR-mice. Mimicking diet-induced overactivation of PI3k signaling by disruption of the PIP3-phosphatase PTEN leads to increased body weight and hyperphagia under normal chow diet. Collectively, our experiments reveal a critical role for HFD-induced, insulin-dependent PI3k activation in VMH neurons to control energy homeostasis.
登录
查看更多内容
影响因子：
16.2
作者：
Dhillon, H;Zigman, JM;Lowelll, BB
通讯作者：
Lowelll, BB
影响因子：
3.8
作者：
Horn, R;Marty, A
通讯作者：
Marty, A
影响因子：
4.8
作者：
Majdic, G;Young, M;Parker, KL
通讯作者：
Parker, KL
影响因子：
29
作者：
Gelling, RW;Morton, GJ;Schwartz, MW
通讯作者：
Schwartz, MW
影响因子：
29
作者：
Koenner, A. Christine;Janoschek, Ruth;Bruening, Jens C.
通讯作者：
Bruening, Jens C.