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ID 115055
Author
Suzuki, Toru Tohoku University
Gao, Junhong Tohoku University
Ishigaki, Yasushi Iwate Medical University
Kondo, Keiichi Tohoku University
Sawada, Shojiro Tohoku University
Izumi, Tomohito Tohoku University
Uno, Kenji Tohoku University
Kaneko, Keizo Tohoku University
Tsukita, Sohei Tohoku University
Takahashi, Kei Tohoku University
Asao, Atsuko Tohoku University
Ishii, Naoto Tohoku University
Imai, Junta Tohoku University
Yamada, Tetsuya Tohoku University
Katagiri, Hideki Tohoku University|Japan Agency for Medical Research and Development
Content Type
Journal Article
Description
Obesity represents chronic inflammatory states promoted by pro-inflammatory M1-macrophage infiltration into white adipose tissue (WAT), thereby inducing insulin resistance. Herein, we demonstrate the importance of an ER stress protein, CHOP, in determining adipose tissue macrophage (ATM) polarity and systemic insulin sensitivity. A high-fat diet (HFD) enhances ER stress with CHOP upregulation in adipocytes. CHOP deficiency prevents HFD-induced insulin resistance and glucose intolerance with ATM M2 predomination and Th2 cytokine upregulation in WAT. Whereas ER stress suppresses Th2 cytokine expression in cultured adipocytes, CHOP knockdown inhibits this downregulation. In contrast, macrophage responsiveness to Th1/Th2 cytokines is unchanged regardless of whether CHOP is expressed. Furthermore, bone marrow transplantation experiments showed recipient CHOP to be the major determinant of ATM polarity. Thus, CHOP in adipocytes plays important roles in ATM M1 polarization by altering WAT micro-environmental conditions, including Th2 cytokine downregulation. This molecular mechanism may link adipose ER stress with systemic insulin resistance.
Journal Title
Cell Reports
ISSN
22111247
Publisher
Elsevier
Volume
18
Issue
8
Start Page
2045
End Page
2057
Published Date
2017-02-21
Rights
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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DOI (Published Version)
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language
eng
TextVersion
Publisher
departments
Institute of Advanced Medical Sciences