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

doi:10.1016/j.cmet.2010.05.002

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 journal › Article › peer-review

91 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 language	English (US)
Pages (from-to)	88-95
Number of pages	8
Journal	Cell Metabolism
Volume	12
Issue number	1
DOIs	https://doi.org/10.1016/j.cmet.2010.05.002
State	Published - Jul 7 2010

Keywords

HUMDISEASE
MOLNEURO

ASJC Scopus subject areas

Physiology
Molecular Biology
Cell Biology

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10.1016/j.cmet.2010.05.002

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@article{4686c7bdf2a542d581f74e4002242663,

title = "PI3K signaling in the ventromedial hypothalamic nucleus is required for normal energy homeostasis",

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.",

keywords = "HUMDISEASE, MOLNEURO",

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

note = "Funding Information: We would like to thank the Mouse Metabolic Phenotyping Core at UTSW Medical Center (supported by NIH PL1 DK081182 and UL1 RR024923). This work was supported by grants from Canadian Institute of Health Research (Y.X.) and the NIH (K99 DK085330 to Y.X.; 1F32DK066972 to J.W.H.; R01DK071051 to B.B.L.; RL1 DK081185, R37DK53301, and R01DK071320 to J.K.E.; and R01CA134502-01 to J.J.Z.); by UTSW Medical Center Disease-Oriented Clinical Scholars Program (J.M.Z.); by the V Foundation (J.J.Z.); by an ADA research grant (1-07-RA-41 to J.K.E. and L.G.); and by an ADA Smith Family Foundation Pinnacle Program Award to J.K.E. ",

year = "2010",

month = jul,

day = "7",

doi = "10.1016/j.cmet.2010.05.002",

language = "English (US)",

volume = "12",

pages = "88--95",

journal = "Cell Metabolism",

issn = "1550-4131",

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T1 - PI3K signaling in the ventromedial hypothalamic nucleus is required for normal energy homeostasis

AU - Xu, Yong

AU - Hill, Jennifer W.

AU - Fukuda, Makoto

AU - Gautron, Laurent

AU - Sohn, Jong Woo

AU - Kim, Ki Woo

AU - Lee, Charlotte E.

AU - Choi, Michelle J.

AU - Lauzon, Danielle A.

AU - Dhillon, Harveen

AU - Lowell, Bradford B.

AU - Zigman, Jeffrey M.

AU - Zhao, Jean J.

AU - Elmquist, Joel K.

N1 - Funding Information: We would like to thank the Mouse Metabolic Phenotyping Core at UTSW Medical Center (supported by NIH PL1 DK081182 and UL1 RR024923). This work was supported by grants from Canadian Institute of Health Research (Y.X.) and the NIH (K99 DK085330 to Y.X.; 1F32DK066972 to J.W.H.; R01DK071051 to B.B.L.; RL1 DK081185, R37DK53301, and R01DK071320 to J.K.E.; and R01CA134502-01 to J.J.Z.); by UTSW Medical Center Disease-Oriented Clinical Scholars Program (J.M.Z.); by the V Foundation (J.J.Z.); by an ADA research grant (1-07-RA-41 to J.K.E. and L.G.); and by an ADA Smith Family Foundation Pinnacle Program Award to J.K.E.

PY - 2010/7/7

Y1 - 2010/7/7

N2 - 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.

AB - 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.

KW - HUMDISEASE

KW - MOLNEURO

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DO - 10.1016/j.cmet.2010.05.002

M3 - Article

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AN - SCOPUS:77956627976

SN - 1550-4131

VL - 12

SP - 88

EP - 95

JO - Cell Metabolism

JF - Cell Metabolism

IS - 1

ER -

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

Abstract

Keywords

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