Amelioration of adipose inflammation and insulin resistance in aged and diet-induced obese mice by targeting programmed death-1+ adipose T cells

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461116
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Hyogo Medical University (2014-2015); Keio University (2013)
• Principal Investigator: Shinmura Ken 兵庫医科大学, 医学部, 教授 (70206332)
• 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)
• Project Period (FY): 2013-04-01 – 2016-03-31
• 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

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.

Free Research Field

医歯薬学