2013 Fiscal Year Final Research Report
Transcription factor KLF5 in the regulation of appetite control
| Project/Area Number |
24790738
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KOJIMA Toshiya 東京大学, 医学部附属病院, 助教 (30625588)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | 転写因子KLF5 / 摂食調節 / AgRP / メタボリックシンドローム |
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| Research Abstract |
It is vital to elucidate the molecular mechanisms underlying obesity. The arcuate nucleus in the hypothalamus integrates control appetite. It contains neurons expressing Agouti-related peptide (AgRP) that promote food intake. Kruppel-like factor 5 (KLF5) and Agouti-related peptide (AgRP) are co-existing in the arcuate nucleus of the hypothalamus. KLF5 inhibits FoxO1 function which activates Agrp promoter. Moreover, the SUMOylateion of KLF5 is essential for its inhibition of Agrp by suppressing FoxO1.
The phenotype of Agrp neuron-specific Klf5 deletion mice indicates that Agrp neuron-specific Klf5 deletion mice have more body weight gain, because of more food intake. Our results suggest a model, in which KLF5 suppress activation of AgRP neurons by counteracting with FoxO1 in the hypothalamus, thereby inhibiting food intake. KLF5 appears to be important for both central and peripheral control of energy metabolism.
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