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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2010-3-22
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pubmed:abstractText |
Both insulin and leptin signaling converge on phosphatidylinositol 3-OH kinase [PI(3)K]/3-phosphoinositide-dependent protein kinase-1 (PDK-1)/protein kinase B (PKB, also known as Akt) in proopiomelanocortin (POMC) neurons. Forkhead box-containing protein-O1 (FoxO1) is inactivated in a PI(3)K-dependent manner. However, the interrelationship between PI(3)K/PDK-1/Akt and FoxO1, and the chronic effects of the overexpression of FoxO1 in POMC neurons on energy homeostasis has not been elucidated. To determine the extent to which PDK-1 and FoxO1 signaling in POMC neurons was responsible for energy homeostasis, we generated POMC neuron-specific Pdk1 knockout mice (POMCPdk1(-/-)) and mice selectively expressing a constitutively nuclear (CN)FoxO1 or transactivation-defective (Delta256)FoxO1 in POMC neurons (CNFoxO1(POMC) or Delta256FoxO1(POMC)). POMCPdk1(-/-) mice showed increased food intake and body weight accompanied by decreased expression of Pomc gene. The CNFoxO1(POMC) mice exhibited mild obesity and hyperphagia compared with POMCPdk1(-/-) mice. Although expression of the CNFoxO1 made POMCPdk1(-/-) mice more obese due to excessive suppression of Pomc gene, overexpression of Delta256FoxO1 in POMC neurons had no effects on metabolic phenotypes and Pomc expression levels of POMCPdk1(-/-) mice. These data suggest a requirement for PDK-1 and FoxO1 in transcriptional regulation of Pomc and food intake.
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1522-1555
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pubmed:author |
pubmed-author:CaoYonghengY,
pubmed-author:ChuaStreamsonSJr,
pubmed-author:HayashiYoshitakeY,
pubmed-author:IskandarKristyK,
pubmed-author:ItohHiroshiH,
pubmed-author:KasugaMasatoM,
pubmed-author:NakataMasanoriM,
pubmed-author:NambiK SKS,
pubmed-author:NodaTetsuoT,
pubmed-author:OgawaWataruW,
pubmed-author:OkiMiyoM,
pubmed-author:TakanoEisukeE,
pubmed-author:YadaToshihikoT,
pubmed-author:ZhangChangliangC
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pubmed:issnType |
Electronic
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pubmed:volume |
298
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
E787-98
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pubmed:meshHeading |
pubmed-meshheading:20103739-Adrenocorticotropic Hormone,
pubmed-meshheading:20103739-Animals,
pubmed-meshheading:20103739-Chromatin,
pubmed-meshheading:20103739-Eating,
pubmed-meshheading:20103739-Fluorescent Antibody Technique,
pubmed-meshheading:20103739-Forkhead Transcription Factors,
pubmed-meshheading:20103739-Gene Expression Regulation,
pubmed-meshheading:20103739-Glucose Tolerance Test,
pubmed-meshheading:20103739-Immunoprecipitation,
pubmed-meshheading:20103739-Mice,
pubmed-meshheading:20103739-Mice, Knockout,
pubmed-meshheading:20103739-Mice, Transgenic,
pubmed-meshheading:20103739-Motor Activity,
pubmed-meshheading:20103739-Neurons,
pubmed-meshheading:20103739-Obesity,
pubmed-meshheading:20103739-Oxygen Consumption,
pubmed-meshheading:20103739-Plasmids,
pubmed-meshheading:20103739-Pro-Opiomelanocortin,
pubmed-meshheading:20103739-RNA,
pubmed-meshheading:20103739-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:20103739-TRPP Cation Channels
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pubmed:year |
2010
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pubmed:articleTitle |
PDK-1/FoxO1 pathway in POMC neurons regulates Pomc expression and food intake.
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pubmed:affiliation |
International Center for Medical Research and Treatment, Kobe University Graduate school of Medicine, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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