2017 Fiscal Year Final Research Report
The role of endoplasmic reticulum stress response in the development of atherosclerosis resulted from obesity and diabetes.
| Project/Area Number |
15K09416
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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 |
Metabolomics
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| Research Institution | Iwate Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
佐々木 章 岩手医科大学, 医学部, 教授 (40275540)
川崎 靖 岩手医科大学, 薬学部, 助教 (60385549)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | 肥満 / インスリン抵抗性 / 小胞体ストレス応答 |
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| Outline of Final Research Achievements |
We examined the gene expressions of visceral adipose tissue related to inflammation and endoplasmic reticulum (ER) stress response in Japanese subjects with morbid obesity. The expressions of TNF-a increased 4.0fold(p=0.0082), CHOP 1.7 fold (p=0.0034), compared to non-obese subjects. These results showed thatinflammation and ER stress response were aggravated in adipose tissue with obesity as reported in animal experiment.
Obesity represents chronic inflammatory states promoted by pro-inflammatory M1-macrophage infiltration into adipose tissue, thereby inducing insulin resistance. Obesity enhances ER stress with CHOP upregulation in adipocytes. CHOP deficiency prevents obesity induced insulin resistancewith M2 macrophage predomination and Th2 cytokine upregulation in WAT. Whereas ER stress suppresses Th2 cytokine expression in cultured adipocytes, CHOP knockdown inhibits this downregulation.This molecular mechanism may link adipose ER stress with systemic insulin resistance.
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| Free Research Field |
代謝学
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