| Project/Area Number |
17590930
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Osaka University |
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Principal Investigator |
NAKAMURA Tadashi Osaka University, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (90252668)
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| Co-Investigator(Kenkyū-buntansha) |
FUNAHASHI Tohru Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (60243234)
KIHARA Shinji Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (20332736)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | aquaporin / glycerol / adipocyte / life-style related disease / glycerol kinase / Foxo 1 / IRE-1 / knockout mouse / 肥満 / IRE1 / インスリン抵抗性 |
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| Research Abstract |
In the present study, we investigated the relationship between AQPap and obesity in mice lacking AQPap. There is no difference in body weight of WT and KO mice, but KO mice become obese after 12 weeks of age. Adipose tissue weights of AQPap KO mice are significantly heavier than WT mice at 20 weeks of age. Histlogical analysis shows an increase in hypertrophic adipocytes in WAT of KO mice. KO mice exhibit whole body insulin resistance associated with obesity. We also demonstrated that knock down of AQPap in 3T3-L1 adipocytes increases intracellular glycerol contents, elevates glycerol kinase activities, enhances oleic acid uptake, and finally results in TG accumulation (PNAS 2005).
Furthermore, we investigated the effect of AQP ap on the differentiation of adipocytes. The stromal vascular cells (SVCs) which are isolated from WAT of WT or AQPap KO mice are differentiated to adipocytes and the adipocytes after 2,4 and 6 days from induction are examined the staining by oil red O and the genetic expression of PPAR. There are no differences between SVC adipocytes derived from WT and KO mice. The medium concentration of glycerol is significantly lower in SVC adipocytes from KO mice than in those from WT mice during the lipolytic state induced by epinephrine. These findings suggest that AQPap is a glycerol channel without the effects on the differentiation of adipocytes. We could also identify a fork-head type transcriptional factor, Foxol, as one of the promoters for AQPap using 3T3-L1 adipocytes or 293 cells and confirm the Foxo 1 binds insulin response element (IRE) 1 site by gel shift assay.
Our series of these results were presented in News ＆ Views of Nature 2005 and moreover, we published the review for AQPap and glycerol metabolism in BBA 2006.
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