| Project/Area Number |
26860687
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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 |
Metabolomics
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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) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 転写因子KLF5 / 摂食調節 / AgRP / FoxO1 / メタボリックシンドローム / KLF5 |
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| Outline of Final Research Achievements |
Increasing prevalence of obesity is an urgent public health challenge. The arcuate nucleus in the hypothalamus integrates control appetite. It contains neurons expressing Agouti-related peptide (AgRP) that promote food intake.
In immunohistochemistry of hypothalamus, Kruppel-like factor 5 (KLF5) was expressed in AgRP neuron. KLF5 inhibited FoxO1 function which activates Agrp promoter.
Agrp neuron-specific Klf5 deletion mice increased food intake and body weight gain. On the other hand, pair-feeding did not induce the significant difference of body weight between wild type mice and Agrp neuron-specific Klf5 deletion mice. These phenotypes indicate that Agrp neuron-specific Klf5 deletion mice had more body weight gain, because of more food intake. 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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