Molecular Characterization of Short-chain Fatty Acid receptor GPR41 and GPR43 in cat
Project/Area Number |
19K06409
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 42020:Veterinary medical science-related
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Research Institution | Nippon Veterinary and Life Science University |
Principal Investigator |
Yamamoto Ichiro 日本獣医生命科学大学, 獣医学部, 准教授 (00424763)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Keywords | ネコ / GPR41 / GPR43 / 短鎖脂肪酸 / FFAR2 / FFAR3 / GPR41/FFAR3 / GPR43/FFAR2 |
Outline of Research at the Start |
本研究課題はネコのGPR41とGPR43の受容体としての機能を細胞内シグナル伝達解析、NanoBiT法による2量体形成解析、発現部位を免疫染色またはIn situ hybridization解析、GPR41とGPR43遺伝子中の一塩基多型(SNP)探索をサーベイヤー解析によって行う。SNP探索により将来肥満するネコを出生時に予測するゲノム診断技術の開発に寄与するものである。
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Outline of Final Research Achievements |
G protein-coupled receptors (GPRs) 41 and 43 were identified and characterized as free fatty acid receptors (FFARs) 3 and 2, respectively. FFAR2 and FFAR3 mediate short-chain fatty acids (SCFAs) as signaling molecules. The present study aimed to molecularly characterize FFAR2 and FFAR3 to study lipid metabolism in the domestic cat. cDNA cloning of cat FFAR2/3 revealed high homology with that in other mammals. Tissue distribution of cat FFAR2 and FFAR3 mRNA was analyzed by qPCR. Inhibition of intracellular cAMP concentrations was observed in cells transfected with cat FFAR2 or FFAR3 and treated with propionate and acetate. Split luciferase assay (NanoBiT) revealed homo/heterodimerization in HEK293 cells transfected with cat FFAR2 and/or FFAR3. These results indicate that the functional receptor proteins, FFAR2 and FFAR3, are expressed in cat tissues and show differential distribution patterns.
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Academic Significance and Societal Importance of the Research Achievements |
ヒト同様、ネコも2型糖尿病が多い動物であり、過度の脂肪が蓄積され肥満した結果、糖尿病を発病する。脂肪を構成する脂肪酸は必須栄養素のみならず、生理機能をもつシグナル伝達物質としても作用する。2003年以降、数々の脂肪酸に対するヒトGタンパク質共役型受容体GPR40、GPR41、 GPR43、 GPR120が発見され、異なる生理作用を介することが明らかとなった。ネコは幼猫期に多量の脂肪酸DHAを必要とする等、他の動物とは異なる脂肪酸の代謝経路を持つことから、本研究では特に短鎖脂肪酸の受容体GPR41とGPR43の機能を分子生物学的な解析を行なった。
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Report
(4 results)
Research Products
(4 results)