PI3K Signaling in the Ventromedial Hypothalamic Nucleus Is Required for Normal Energy Homeostasis

Phosphatidyl inositol 3-kinase (PI3K) signaling in the hypothalamus has been implicated in the regulation of energy homeostasis, but the critical brain sites where this intracellular signal integrates various metabolic cues to regulate food intake and energy expenditure are unknown. Here, we show th...

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Bibliographic Details
Published in:Cell metabolism 2010-07, Vol.12 (1), p.88-95
Main Authors: Xu, Yong, Hill, Jennifer W., Fukuda, Makoto, Gautron, Laurent, Sohn, Jong-Woo, Kim, Ki-Woo, Lee, Charlotte E., Choi, Michelle J., Lauzon, Danielle A., Dhillon, Harveen, Lowell, Bradford B., Zigman, Jeffrey M., Zhao, Jean J., Elmquist, Joel K.
Format: Article
Language:English
Subjects:
Animals
Appetite Depressants - pharmacology
Dietary Fats - pharmacology
Energy Metabolism
Homeostasis
HUMDISEASE
Leptin - pharmacology
Male
Mice
Mice, Knockout
MOLNEURO
Neurons - metabolism
Obesity - etiology
Obesity - metabolism
Phosphatidylinositol 3-Kinases - antagonists & inhibitors
Phosphatidylinositol 3-Kinases - genetics
Phosphatidylinositol 3-Kinases - metabolism
Signal Transduction
Ventromedial Hypothalamic Nucleus - enzymology
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Summary:Phosphatidyl inositol 3-kinase (PI3K) signaling in the hypothalamus has been implicated in the regulation of energy homeostasis, but the critical brain sites where this intracellular signal integrates various metabolic cues to regulate food intake and energy expenditure are unknown. Here, we show that mice with reduced PI3K activity in the ventromedial hypothalamic nucleus (VMH) are more sensitive to high-fat diet-induced obesity due to reduced energy expenditure. In addition, inhibition of PI3K in the VMH impaired the ability to alter energy expenditure in response to acute high-fat diet feeding and food deprivation. Furthermore, the acute anorexigenic effects induced by exogenous leptin were blunted in the mutant mice. Collectively, our results indicate that PI3K activity in VMH neurons plays a physiologically relevant role in the regulation of energy expenditure. ► Mice lacking PI3K in VMH SF1 neurons are more susceptible to diet-induced obesity ► PI3K in VMH SF1 neurons is required for regulating thermogenic responses to diet ► PI3K in VMH SF1 neurons mediates the acute effects of leptin
ISSN:1550-4131
1932-7420
DOI:10.1016/j.cmet.2010.05.002