PI3K signaling in the ventromedial hypothalamic nucleus is required for normal energy homeostasis

Yong Xu, Jennifer W. Hill, Makoto Fukuda, Laurent Gautron, Jong Woo Sohn, Ki Woo Kim, Charlotte E. Lee, Michelle J. Choi, Danielle A. Lauzon, Harveen Dhillon, Bradford B. Lowell, Jeffrey M. Zigman, Jean J. Zhao, Joel K. Elmquist

Research output: Contribution to journalArticle

76 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)88-95
Number of pages8
JournalCell Metabolism
Volume12
Issue number1
DOIs
StatePublished - Jul 7 2010

Keywords

  • HUMDISEASE
  • MOLNEURO

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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    Xu, Y., Hill, J. W., Fukuda, M., Gautron, L., Sohn, J. W., Kim, K. W., Lee, C. E., Choi, M. J., Lauzon, D. A., Dhillon, H., Lowell, B. B., Zigman, J. M., Zhao, J. J., & Elmquist, J. K. (2010). PI3K signaling in the ventromedial hypothalamic nucleus is required for normal energy homeostasis. Cell Metabolism, 12(1), 88-95. https://doi.org/10.1016/j.cmet.2010.05.002