Elucidation of molecular basis common to cardiovascular disorders associated with aging and metabolic syndrome
Project/Area Number |
15H04825
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Cardiovascular medicine
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Research Institution | Keio University |
Principal Investigator |
SANO MOTOAKI 慶應義塾大学, 医学部(信濃町), 准教授 (30265798)
|
Research Collaborator |
SHIRAKAWA Kohsuke 慶應義塾大学, 医学部循環器内科研究室, 大学院生
YAMAMOTO Tsunehisa 慶應義塾大学, 医学部循環器内科研究室, 大学院生
|
Project Period (FY) |
2015-04-01 – 2018-03-31
|
Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2015: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
|
Keywords | 免疫老化 / 肥満 / T細胞 / マクロファージ / 高脂肪食 / 内臓脂肪 / B細胞 / 養子免疫細胞移入 / 糖尿病 / 慢性炎症 / 老化 / オステオポンチン / 加齢 / 細胞老化 / メタボリックシンドローム |
Outline of Final Research Achievements |
Chronic inflammation in visceral adipose tissue (VAT) precipitates the development of cardiometabolic disorders. Here, we have determined that a high-fat diet (HFD) caused a preferential increase and accumulation of CD44hiCD62LloCD4+ T cells that constitutively express PD-1 and CD153 in VAT. These cells possessed characteristics of cellular senescence and produced large amounts of osteopontin (OPN) in a PD-1-resistant manner. The features of these T cells were highly reminiscent of senescence-associated CD4+ T cells that normally increase with age. Adoptive transfer of CD153+PD-1+CD44hiCD4+ T cells from HFD-fed WT, but not Spp1-deficient, mice into the VAT of lean mice fed a normal diet recapitulated the essential features of VAT inflammation and insulin resistance. Our results demonstrate that a distinct CD153+PD-1+CD44hiCD4+ T cell population causes VAT inflammation by producing large amounts of OPN. This finding suggests a link between visceral adiposity and immune aging.
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] Negative legacy of obesity2017
Author(s)
Shirakawa K, Endo J, Katsumata Y, Yamamoto T, Kataoka M, Isobe S, Yoshida N, Fukuda K, Sano M
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Journal Title
PLoS One
Volume: 12(10)
Issue: 10
Pages: e0186303-e0186303
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Obesity accelerates T-cell senescence in visceral adipose tissue2016
Author(s)
Shirakawa K, Yan X, Shinmura K, Endo J, Kataoka M, Katsumata Y, Yamamoto T, Anzai A, Isobe S, Yoshida N, Itoh H, Manabe I, Sekai M, Hamazaki Y, Fukuda K, Minato N, and Sano M.
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Journal Title
J Clin Invest.
Volume: 126
Issue: 12
Pages: 4626-4639
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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