| Project/Area Number |
16K09784
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Metabolomics
|
|---|
| Research Institution | Hiroshima University |
|---|
Principal Investigator |
Nakatsu Yusuke 広島大学, 医系科学研究科(医), 講師 (20452584)
|
|---|
| Project Period (FY) |
2016-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
|---|
| Keywords | Pin1 / 熱産生 / PRDM16 / UCP-1 / 肥満 |
|---|
| Outline of Final Research Achievements |
In this study, we reveal that Pin1 suppresses thermogenesis in scWAT and BAT. After cold stimulation, Pin1 KO mice showed the higher expression levels of thermogenic genes in scWAT and BAT than WT mice. Interestingly, we found that Pin1 associates with transcriptional co-factor PRDM16 which is essential for the induction of thermogenic genes. Pin1 overexpressions suppressed the expression of PRDM16 protein, while Pin1 knockdown increased. Proteasome ihibitor rescued the decrease of PRDM16 by Pin1 overexpressions, suggesting that Pin1 promotes the degradation of PRDM16 through ubiquitin-proteasome system. In primary adipocytes, Pin1 deficiency also upregualted the expression of UCP-1 by CL316243. In adddition, PRDM16 knockdown abrogated the increase of UCP-1 protein by Pin1 deficiency.
In summary, Pin1 suppresses the thermogeneis through regulating the stability og PRDM16 protein.
|
| Academic Significance and Societal Importance of the Research Achievements |
肥満になると脂肪組織での熱産生が抑制され、ますます太りやすくなると考えられている。しかしながら、肥満時に熱産生が抑制される機序については、ほとんど明らかにされていない。本研究では、肥満時に発現が増加したPin1がPRDM16の分解を促進し、熱産生を抑制することを明らかにした。従って、脂肪組織のPin1発現量を抑制することができれば、抗肥満作用につながると考えられる。
|
