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 |
Section | 一般 |
Research Field |
Metabolomics
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Research Institution | Iwate Medical University |
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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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | 肥満 / インスリン抵抗性 / 小胞体ストレス応答 / 小胞体ストレス / 酸化ストレス / 動脈硬化 / 脂肪細胞 |
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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Report
(4 results)
Research Products
(25 results)
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[Journal Article] Serum cystatin C level is associated with carotid arterial wall elasticity in subjects with type 2 diabetes mellitus: A potential marker of early-stage atherosclerosis.2018
Author(s)
Kaneko R, Sawada S, Tokita A, Honkura R, Tamura N, Kodama S, Izumi T, Takahashi K, Uno K, Imai J, Yamada T, Miyachi Y, Hasegawa H, Kanai H, Ishigaki Y, Katagiri H
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Journal Title
Diabetes Research and Clinical Practice
Volume: 139
Pages: 43-51
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Association of epicardial adipose tissue with serum level of cystatin C in type 2 diabetes.2017
Author(s)
Murai T, Takebe N, Nagasawa K, Todate Y, Nakagawa R, Nakano R, Hangai M, Hasegawa Y, Takahashi Y, Yoshioka K, Ishigaki Y.
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Journal Title
PLoS One
Volume: 12
Issue: 9
Pages: e0184723-e0184723
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Neuronal signals regulate obesity induced beta-cell proliferation by FoxM1 dependent mechanism.2017
Author(s)
Yamamoto J, Imai J, Izumi T, Takahashi H, Kawana Y, Takahashi K, Kodama S, Kaneko K, Gao J, Uno K, Sawada S, Asano T, Kalinichenko VV, Susaki EA, Kanzaki M, Ueda HR, Ishigaki Y, Yamada T, Katagiri H
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Journal Title
Nature Communications
Volume: 8
Issue: 1
Pages: 1930-1930
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] ES Stress Protein CHOP Mediates Insulin Resistanse by Modulating Adipose Tissue Macrophage Polarity.2017
Author(s)
Suzuki T, Gao J, Ishigaki Y, Kondo K, Sawada S, Izumi T, Uno K, Kaneko K, Tsukita S, Takahashi K, Asao A, Ishii N, Imai J, Yamada T, Oyadomarai S, Katagiri H
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Journal Title
Cell Rep
Volume: 18
Issue: 8
Pages: 2045-2057
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Lipoprotein Lipase Deficiency (R243H) in a Type 2 Diabetes Patient with Multiple Arterial Aneurysms2016
Author(s)
Suzuki T, Sawada S, Ishigaki Y, Tsukita S, Kodama S, Sugisawa T, Imai J, Yamada T, Yamaguchi T, Murano T, Katagiri H.
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Journal Title
Internal Medicine
Volume: 55
Issue: 9
Pages: 1131-1136
DOI
NAID
ISSN
0918-2918, 1349-7235
Related Report
Peer Reviewed
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[Journal Article] Association of Advanced Glycation End Products with coronary Artery Calcification in Japanese Subjects with Type 2 Diabetes as Assessed by Skin Autofluorescence.2016
Author(s)
52.Hangai M, Takebe N, Honma H, Sasaki A, Chida A, Nakano R, Togashi H, Nakagawa R, Oda T, Matsui M, Yashiro S, Nagasawa K, Kajiwara T, Takahashi K, Takahashi Y, Satoh J, Ishigaki Y.
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Journal Title
J Atheroscler Thromb
Volume: Mar,19
NAID
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] A hepatic amino acid/mTOR/S6K-dependent signalling pathway modulates systemic lipid metabolism via neuronal signals2015
Author(s)
Uno K, Yamada T, Ishigaki Y, Imai J, Hasegawa Y, Sawada S, Kaneko K, Ono H, Asano T, Oka Y, Katagiri H
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Journal Title
Nat Commun
Volume: 6
Issue: 1
Pages: 7940-7940
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Impacts of the Great East Japan Earthquake on diabetic patients.2015
Author(s)
anaka M, Imai J, Satoh M, Hashimoto T, Izumi T, Sawada S, Uno K, Hasegawa Y, Kaneko K, Yamada T, Ishigaki Y, Imai Y and Katagiri H.
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Journal Title
J Diabetes Invest.
Volume: 印刷中
Issue: 5
Pages: 1-10
DOI
Related Report
Peer Reviewed / Open Access
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