2015 Fiscal Year Final Research Report
The regulation of bone metabolism by arcuate nucleus in hypothalamus
| Project/Area Number |
24592277
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2016-03-31
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| Keywords | 骨代謝 / 弓状核 / AgRP ニューロン / ＰＤＫ１ / ＦｏｘＯ１ / ＩＧＦ－１ / 摂食調節 / 成長ホルモン |
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| Outline of Final Research Achievements |
Bone metabolism s regulated substantially by the central nervous system. The agouti-related protein (AgRP) neurons in hypothalamic arcuate nucleus play an essential role in energy metabolism. Previously, we reported that the PDK1-FoxO1 pathway in AgRP neurons regulates the feeding. However, its relationship to bone metabolism remains unknown. This study aimed to explore the role of AgRP neuron’s PDK1 and FoxO1 in bone metabolism by analyzing AGRP neuron-specific PDK1 knockout mice and those with additional expression of dominant negative (DN) FoxO1. In KO mice, as compared with Agrp Cre mice, the stature and femur length were shorter. The bone formation was delayed via the hyposecretion of GH and IGF-1. Moreover, these disorders of bone metabolism in KO mice were rescued by expression of DN FoxO1. These results indicate that FoxO1 regulates PDK1 in AgRP neurons and that this neuronal signaling is linked to regulation of bone metabolism.
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| Free Research Field |
生理学
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