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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2004-7-1
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pubmed:abstractText |
Leptin is an adipocyte-derived hormone that plays a key role in energy homeostasis, yet resistance to leptin is a feature of most cases of obesity in humans and rodents. In vitro analysis suggested that the suppressor of cytokine signaling-3 (Socs3) is a negative-feedback regulator of leptin signaling involved in leptin resistance. To determine the functional significance of Socs3 in vivo, we generated neural cell-specific SOCS3 conditional knockout mice using the Cre-loxP system. Compared to their wild-type littermates, Socs3-deficient mice showed enhanced leptin-induced hypothalamic Stat3 tyrosine phosphorylation as well as pro-opiomelanocortin (POMC) induction, and this resulted in a greater body weight loss and suppression of food intake. Moreover, the Socs3-deficient mice were resistant to high fat diet-induced weight gain and hyperleptinemia, and insulin-sensitivity was retained. These data indicate that Socs3 is a key regulator of diet-induced leptin as well as insulin resistance. Our study demonstrates the negative regulatory role of Socs3 in leptin signaling in vivo, and thus suppression of Socs3 in the brain is a potential therapy for leptin-resistance in obesity.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Dietary Fats,
http://linkedlifedata.com/resource/pubmed/chemical/Leptin,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Socs3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Stat3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Suppressor of Cytokine Signaling...,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1078-8956
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
739-43
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15208705-Animals,
pubmed-meshheading:15208705-Brain Chemistry,
pubmed-meshheading:15208705-DNA-Binding Proteins,
pubmed-meshheading:15208705-Dietary Fats,
pubmed-meshheading:15208705-Eating,
pubmed-meshheading:15208705-Female,
pubmed-meshheading:15208705-Insulin Resistance,
pubmed-meshheading:15208705-Leptin,
pubmed-meshheading:15208705-Male,
pubmed-meshheading:15208705-Mice,
pubmed-meshheading:15208705-Obesity,
pubmed-meshheading:15208705-Phosphorylation,
pubmed-meshheading:15208705-Repressor Proteins,
pubmed-meshheading:15208705-STAT3 Transcription Factor,
pubmed-meshheading:15208705-Suppressor of Cytokine Signaling Proteins,
pubmed-meshheading:15208705-Trans-Activators,
pubmed-meshheading:15208705-Transcription Factors,
pubmed-meshheading:15208705-Weight Loss
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pubmed:year |
2004
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pubmed:articleTitle |
Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity.
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pubmed:affiliation |
Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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