DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kloeckener, Tim | ko |
dc.contributor.author | Hess, Simon | ko |
dc.contributor.author | Belgardt, Bengt F. | ko |
dc.contributor.author | Paeger, Lars | ko |
dc.contributor.author | Verhagen, Linda A. W. | ko |
dc.contributor.author | Husch, Andreas | ko |
dc.contributor.author | Sohn, Jong-Woo | ko |
dc.contributor.author | Hampel, Brigitte | ko |
dc.contributor.author | Dhillon, Harveen | ko |
dc.contributor.author | Zigman, Jeffrey M. | ko |
dc.contributor.author | Lowell, Bradford B. | ko |
dc.contributor.author | Williams, Kevin W. | ko |
dc.contributor.author | Elmquist, Joel K. | ko |
dc.contributor.author | Horvath, Tamas L. | ko |
dc.contributor.author | Kloppenburg, Peter | ko |
dc.contributor.author | Bruening, Jens C. | ko |
dc.date.accessioned | 2015-11-20T12:45:27Z | - |
dc.date.available | 2015-11-20T12:45:27Z | - |
dc.date.created | 2014-03-28 | - |
dc.date.created | 2014-03-28 | - |
dc.date.issued | 2011-07 | - |
dc.identifier.citation | NATURE NEUROSCIENCE, v.14, no.7, pp.911 - 918 | - |
dc.identifier.issn | 1097-6256 | - |
dc.identifier.uri | http://hdl.handle.net/10203/201680 | - |
dc.description.abstract | Steroidogenic factor 1 (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 phosphatidylinositol-3-OH kinase (PI3K) signaling in SF-1 neurons and reduces firing frequency in these cells through activation of K(ATP) channels. These effects were abrogated in mice with insulin receptor deficiency restricted to SF-1 neurons (SF-1(Delta IR) mice). Whereas body weight and glucose homeostasis remained the same in SF-1(Delta IR) mice as in controls under a normal chow diet, they were protected from diet-induced leptin resistance, weight gain, adiposity and impaired glucose tolerance. High-fat feeding activated PI3K signaling in SF-1 neurons of control mice, and this response was attenuated in the VMH of SF-1(Delta IR) mice. Mimicking diet-induced overactivation of PI3K signaling by disruption of the phosphatidylinositol-3,4,5-trisphosphate phosphatase PTEN led to increased body weight and hyperphagia under a normal chow diet. Collectively, our experiments reveal that high-fat diet-induced, insulin-dependent PI3K activation in VMH neurons contributes to obesity development. | - |
dc.language | English | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.subject | VENTROMEDIAL HYPOTHALAMIC NUCLEUS | - |
dc.subject | HEPATIC GLUCOSE-PRODUCTION | - |
dc.subject | PROOPIOMELANOCORTIN NEURONS | - |
dc.subject | ARCUATE NUCLEUS | - |
dc.subject | BODY-WEIGHT | - |
dc.subject | FOOD-INTAKE | - |
dc.subject | STEROIDOGENIC FACTOR-1 | - |
dc.subject | NEUROTROPHIC FACTOR | - |
dc.subject | ENERGY HOMEOSTASIS | - |
dc.subject | EXPRESSING NEURONS | - |
dc.title | High-fat feeding promotes obesity via insulin receptor/PI3K-dependent inhibition of SF-1 VMH neurons | - |
dc.type | Article | - |
dc.identifier.wosid | 000292081700020 | - |
dc.identifier.scopusid | 2-s2.0-79959652223 | - |
dc.type.rims | ART | - |
dc.citation.volume | 14 | - |
dc.citation.issue | 7 | - |
dc.citation.beginningpage | 911 | - |
dc.citation.endingpage | 918 | - |
dc.citation.publicationname | NATURE NEUROSCIENCE | - |
dc.identifier.doi | 10.1038/nn.2847 | - |
dc.contributor.localauthor | Sohn, Jong-Woo | - |
dc.contributor.nonIdAuthor | Kloeckener, Tim | - |
dc.contributor.nonIdAuthor | Hess, Simon | - |
dc.contributor.nonIdAuthor | Belgardt, Bengt F. | - |
dc.contributor.nonIdAuthor | Paeger, Lars | - |
dc.contributor.nonIdAuthor | Verhagen, Linda A. W. | - |
dc.contributor.nonIdAuthor | Husch, Andreas | - |
dc.contributor.nonIdAuthor | Hampel, Brigitte | - |
dc.contributor.nonIdAuthor | Dhillon, Harveen | - |
dc.contributor.nonIdAuthor | Zigman, Jeffrey M. | - |
dc.contributor.nonIdAuthor | Lowell, Bradford B. | - |
dc.contributor.nonIdAuthor | Williams, Kevin W. | - |
dc.contributor.nonIdAuthor | Elmquist, Joel K. | - |
dc.contributor.nonIdAuthor | Horvath, Tamas L. | - |
dc.contributor.nonIdAuthor | Kloppenburg, Peter | - |
dc.contributor.nonIdAuthor | Bruening, Jens C. | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | VENTROMEDIAL HYPOTHALAMIC NUCLEUS | - |
dc.subject.keywordPlus | HEPATIC GLUCOSE-PRODUCTION | - |
dc.subject.keywordPlus | PROOPIOMELANOCORTIN NEURONS | - |
dc.subject.keywordPlus | ARCUATE NUCLEUS | - |
dc.subject.keywordPlus | BODY-WEIGHT | - |
dc.subject.keywordPlus | FOOD-INTAKE | - |
dc.subject.keywordPlus | STEROIDOGENIC FACTOR-1 | - |
dc.subject.keywordPlus | NEUROTROPHIC FACTOR | - |
dc.subject.keywordPlus | ENERGY HOMEOSTASIS | - |
dc.subject.keywordPlus | EXPRESSING NEURONS | - |
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