2022 Fiscal Year Final Research Report
Analysis of the mechanism of Th2 lymphocyte-mediated energy expenditure in adipocytes
Project/Area Number |
20K08214
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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 52050:Embryonic medicine and pediatrics-related
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Research Institution | International University of Health and Welfare |
Principal Investigator |
Nakae Jun 国際医療福祉大学, 医学部, 教授 (00344573)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | 肥満 / エネルギー消費 / 皮下脂肪組織 / ベージュ脂肪細胞 / Foxo / Th2リンパ球 / Ccl22 |
Outline of Final Research Achievements |
We generated thermogenic program-accelerating mice (T-QKO), in which Foxo1 is knockout and Foxo3 is hetero-knockout in CD4+ T cells. T-QKO exhibit lean phenotype under HFD due to increased energy expenditure. Cold exposure significantly increased expression of the thermogenic genes (Ppargc1a and Ucp1), Th2 cytokines (Il4 and Il13), and Th2 marker gene (Gata3) in subcutaneous adipose tissue (SC) of T-QKO. Furthermore, Ccr4 expression was significantly increased in Th2 cells of T-QKO, and cold exposure induced Ccl22 expression in SC, leading to increased accumulation of Th2 cell population in SC of T-QKO. These data reveal a mechanism by which cold exposure induces selective recruitment of Th2 cells into SC, leading to regulation of energy expenditure by generating beige adipocyte.
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Free Research Field |
肥満、2型糖尿病
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Academic Significance and Societal Importance of the Research Achievements |
肥満は、エネルギー摂取とエネルギー消費の過度の正のバランスにより発症し、現代における最大の栄養破綻病態である。現在、肥満予防・治療の方策に一つとして、エネルギー消費調節が脂肪細胞を中心に注目を集めている。本研究により、脂肪細胞のベージュ化過程にケモカインCcl22が関与する可能性が示唆された。今後は、Ccl22の生理的役割を明らかにするために、ノックアウトによるCcl22作用の抑制、および、Ccl22の過剰発現による抗肥満効果の有無を解析し、肥満の予防・治療戦略の新たな標的分子としての可能性を探る。
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