| Project/Area Number |
25461116
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Cardiovascular medicine
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| Research Institution | Hyogo Medical University (2014-2015)
Keio University (2013) |
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Principal Investigator |
Shinmura Ken 兵庫医科大学, 医学部, 教授 (70206332)
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| Research Collaborator |
FUKUDA KEIICHI 慶應義塾大学, 医学部, 教授 (20199227)
SANO MOTOAKI 慶應義塾大学, 医学部, 准教授 (30265798)
ENDO JIN 慶應義塾大学, 医学部, 助教 (50398608)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 免疫老化 / 炎症 / T細胞 / インスリン抵抗性 / 肥満 / 脂肪細胞 / 抗体治療 / マクロファージ / 脂肪組織 |
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| Outline of Final Research Achievements |
Obesity is associated with accelerated biological aging and predisposes to the early onset of aging-related diseases. We investigate the mechanisms of how obesity accelerates aging. Diet-induced and age-related adiposity were associated with an accumulation of Programmed Death-1(PD-1)+ memory phenotype(MP) CD4+ T cells having features of senescence in visceral adipose tissue(VAT). The PD-1+ MP CD4+ T cells stimulated macrophage infiltration and promoted M1 macrophage polarization, while reducing regulatory T cells in VAT. Immunological depletion of PD-1+ T cells attenuated adipose inflammation and improved insulin resistance in diet-induced obese mice, while adoptive transfer of PD-1+ MP CD4+ T cells in VAT induced adipose inflammation and insulin resistance in non-obese mice. Adipose macrophages was involved in the development of PD-1+ MP CD4+ T cells. We proposed that T cell senescence originating in VAT contributes to the mechanism of how obesity causes aging.
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