Elucidation of the mechanism of adaptive thermogenesis disorder by selenoprotein P
| Project/Area Number |
18K16224
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | セレノプロテインP / 適応熱産生 / 還元ストレス / 褐色脂肪細胞 / ノルアドレナリン / 活性酸素 / 褐色脂肪組織 / 活性酸素種 |
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| Outline of Final Research Achievements |
We investigated the effect of selenoprotein P on adaptive thermogenesis in brown adipose tissue and clarified the following.
(1) Selenoprotein P deficient mice exhibited higher body temperature and accumulation of sulfenylated UCP1, which is an active form, during cold exposure. (2) Noradrenaline-responsive heat generation was enhanced in selenoprotein P-deficient brown adipocytes, whereas selenoprotein P administration to brown adipocytes impaired it. (3) Administration of noradrenaline to brown adipocytes induced physiological reactive oxygen species production that stimulates heat production. Selenoprotein P has eliminated this useful reactive oxygen species.
This study revealed that selenoprotein P induces reductive stress and impairs heat production due to its excessive antioxidant capacity.
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| Academic Significance and Societal Importance of the Research Achievements |
エネルギー代謝の亢進を介した肥満症治療を目的として、多くの研究者によって褐色脂肪組織の分化・活性制御機構の解明が試みられている。一方で2型糖尿病患者や高齢者においてはその熱産生活性が低下していることが知られており、またそのメカニズムは未だ明らかではない。本研究では、抗酸化タンパクとして知られていたセレノプロテインPが熱産生を刺激する生理的な活性酸素を消去することで熱産生障害を障害することを明らかにした。2型糖尿病や加齢に伴って産生が亢進するセレノプロテインPは、これらの病態と褐色脂肪活性抑制を結びつける分子となる可能性があり、持続的で効果的な慢性代謝疾患改善薬の治療標的となり得る。
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Report
(4 results)
Research Products
(7 results)
