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Article Dans Une Revue Nature Neuroscience Année : 2011

High-fat Feeding Promotes Obesity via Insulin Receptor/PI3k-Dependent Inhibition of SF-1 VMH Neurons

Résumé

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-1∆IR-mice). While body weight and glucose homeostasis remain unaltered in SF-1∆IR-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-1∆IR-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.
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hal-00648047 , version 1 (05-12-2011)

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Tim Klöckener, Simon Hess, Bengt F. Belgardt, Lars Paeger, Linda A. Verhagen, et al.. High-fat Feeding Promotes Obesity via Insulin Receptor/PI3k-Dependent Inhibition of SF-1 VMH Neurons. Nature Neuroscience, 2011, ⟨10.1038/nn.2847⟩. ⟨hal-00648047⟩

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