| Project/Area Number |
16K20174
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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 |
Obstetrics and gynecology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Ueda Kazutaka 東京大学, 医学部附属病院, 特任助教 (60375798)
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| Co-Investigator(Renkei-kenkyūsha) |
TAKIMOTO Eiki 東京大学, 医学部附属病院, 講師 (20709513)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | エストロゲン / 中枢神経系 / 肥満 / 女性ホルモン / 褐色脂肪 / 糖尿病 / 中枢神経 / シグナル伝達 / 性ステロイドホルモン |
|---|
| Outline of Final Research Achievements |
A novel knock-in mouse line with the selective blockade of the membrane-initiated estrogen receptor (ER) pathway was employed, and we found that the lack of this pathway precipitated excessive weight gain and glucose intolerance independent of food intake, and that this was accompanied by impaired adaptive thermogenesis and reduced physical activity. Notably, the central activation of protein phosphatase (PP) 2A improved metabolic disorders induced by the lack of membrane-initiated ER signaling. Furthermore, the anti-obesity effect of estrogen replacement in a murine menopause model was abolished by central PP2A inactivation. These findings define a critical role for membrane-initiated ER signaling in metabolic homeostasis via the central action of PP2A.
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