| Project/Area Number |
18590988
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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 | Kinki University (2007)
Kobe University (2006) |
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Principal Investigator |
SAKAUE Hiroshi Kinki University, School of Medicine Division of Pharmacology, Lecturer (60372645)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,790,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Adiopocyte / Obesity / Metabolic syndrome / Transcription factor / KLF15 / 肥満 / エネルギー代謝 / ノックアウトマウス / 転写調節 / Skp2 / 細胞周期 |
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| Research Abstract |
1. KLF15 expression during the development of obesity
We have shown that the expression of the KLF15 gene is markedly down-regulated during the development of obesity in ob/ob mice and high fat-diet mice.
2. Construction of adipocyte-specific KLF15 transgenic mice
We have made the 'adipocyte-specific KLF15 transgenic mice under the aP2-promoter. The amounts of KLF15 were increased by an 〜1-fold or 〜3-fold increase in white adipose tissue in line 1 or line 3 transgenic mice, respectively
3. Metabolic analysis in adipocyte-specific KLF15 transgenic mice fed a normal chaw diet. The mass of white adipose tissue did not differ significantly between wild-type mice and KLF15 transgenic mice fed a normal chaw diet. However, the plasma concentration of adiponectin decreased in KLF15 transgenic mice.
4. Metabolic analysis in adipocyte-specific KLF15 transgenic mice fed a high fat diet
The high fat diet increased the adipocyte mass in wild-type mice. In contrast, maintain of adipocyte-specific KLF15 transgenic mice on the high fat diet did not increase body weight and adipocyte mass. Moreover, an oral glucose tolerance test revealed marked glucose tolerance in adipocyte-specific KLF15 transgenic mice.
5. Metabolic analysis in adipocyte-specific KIF15 transgenic ob/ob mice
We generated ob/ob mice with adipocyte-specific overexpression of KLF15. ob/ob mice with adipocyte-specific overexpression of KLF15 were found to smaller the their ob/ob litermates. This difference in body weight was attributable at least in part to smaller white adipose tissue in the former animals.
6. Role of KLF15 on SCD1 expression
Feeding with the high fat diet resulted in a marked up-regulation of the amount of SCD1 in white adipose tissue. This up-regulation of SCD1 during the development of obesity was not observed in adipocyte-specific KLF15 transgenic mice. In conclusion, KLF15 regulates adipocyte hypertrophy via the expression of SCD1/
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