| Project/Area Number |
20790316
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Research Institute, International Medical Center of Japan |
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Principal Investigator |
DAI Chida Research Institute, International Medical Center of Japan, 研究所, 室長 (90312842)
|
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| Project Period (FY) |
2008 – 2010
|
| Project Status |
Completed (Fiscal Year 2010)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | HPA axis / メタボリックシンドローム / 肥満 / インスリン抵抗性 / 遺伝子改変マウス |
|---|
| Research Abstract |
Bone marrow mesenchymal stem cells (MSCs) are multipotent cells, which give rise to adipocytes and osteoblasts. Within the bone marrow, the differentiation of MSCs into adipocytes or osteoblasts is competitively balanced; mechanisms that promote one cell fate actively suppress mechanisms that induce the alternative lineage. Glucocorticoids (GCs) are used clinically in many situations to treat various immune-mediated diseases, but their long-term administration is associated with multiple metabolic side effects, including osteoporosis and obesity. However, the role of endogenous glucocorticoid, which is synthesized in the adrenal cortex under the exclusive regulation of ACTH, in metabolism and energy balance is not fully elucidated. To analyze the role of endogenous glucocorticoid in metabolism and energy balance, we analyzed MC2R^<-/-> and CRH^<-/-> mice as models of chronic adrenal insufficiency. MC2R^<-/-> mice had lean bodies in old age and reduced fat mass. Adipose tissue weight was decreased in MC2R^<-/-> mice, while adipocyte size in epididymal white adipose tissue were comparable between MC2R^<-/-> mice and MC2R^<+/-> controls, suggesting that white adipose cell number is decreased in MC2R^<-/-> mice compared to MC2R^<+/-> controls. Both MC2R^<-/-> and CRH^<-/-> mice were resistance to high-fat diet-induced obesity and insulin resistance, and they exhibited a high bone mass phenotype in old age. Our results are consistent with the proposed roles of glucocorticoid in the differentiation of MSCs into adipocytes or osteoblasts, i.e. blocks osteogenic differentiation and promotes adipogenic differentiation.
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