PI3K Signaling in the Ventromedial Hypothalamic Nucleus Is Required for Normal Energy Homeostasis
Autor: | Ki Woo Kim, Jeffrey M. Zigman, Jennifer W. Hill, Laurent Gautron, Danielle A. Lauzon, Joel K. Elmquist, Charlotte E. Lee, Michelle J. Choi, Jean J. Zhao, Bradford B. Lowell, Jong Woo Sohn, Makoto Fukuda, Yong Xu, Harveen Dhillon |
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Rok vydání: | 2010 |
Předmět: |
Leptin
Male medicine.medical_specialty Physiology Mutant HUMDISEASE Biology MOLNEURO Energy homeostasis Article 03 medical and health sciences Mice Phosphatidylinositol 3-Kinases 0302 clinical medicine Internal medicine Appetite Depressants medicine Animals Homeostasis Obesity Molecular Biology PI3K/AKT/mTOR pathway 030304 developmental biology Phosphoinositide-3 Kinase Inhibitors Mice Knockout Neurons 0303 health sciences Cell Biology Dietary Fats Endocrinology Hypothalamus Ventromedial Hypothalamic Nucleus Signal transduction Energy Metabolism 030217 neurology & neurosurgery Intracellular Signal Transduction |
Zdroj: | Cell Metabolism. 12(1):88-95 |
ISSN: | 1550-4131 |
DOI: | 10.1016/j.cmet.2010.05.002 |
Popis: | SummaryPhosphatidyl 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. |
Databáze: | OpenAIRE |
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