ER Stress Protein CHOP Mediates Insulin Resistance by Modulating Adipose Tissue Macrophage Polarity

Autor: Shojiro Sawada, Kei Takahashi, Atsuko Asao, Keiichi Kondo, Seiichi Oyadomari, Naoto Ishii, Keizo Kaneko, Toru Suzuki, Sohei Tsukita, Tomohito Izumi, Tetsuya Yamada, Yasushi Ishigaki, Kenji Uno, Hideki Katagiri, Junhong Gao, Junta Imai
Rok vydání: 2017
Předmět:
0301 basic medicine
medicine.medical_specialty
Adipose Tissue
White
macrophage polarization
Macrophage polarization
Down-Regulation
Adipose tissue
White adipose tissue
CHOP
Biology
Diet
High-Fat
Endoplasmic Reticulum
General Biochemistry
Genetics and Molecular Biology
M2 macrophage
Mice
03 medical and health sciences
Th2 Cells
0302 clinical medicine
Insulin resistance
Downregulation and upregulation
Internal medicine
insulin resistance
hemic and lymphatic diseases
Glucose Intolerance
Adipocytes
medicine
Animals
Obesity
adipose tissue macrophage
lcsh:QH301-705.5
Inflammation
Macrophages
Macrophage Activation
Th1 Cells
Endoplasmic Reticulum Stress
M2 Macrophage
medicine.disease
Up-Regulation
Mice
Inbred C57BL
030104 developmental biology
Endocrinology
lcsh:Biology (General)
030220 oncology & carcinogenesis
Unfolded protein response
Cytokines
ER stress
Transcription Factor CHOP
Zdroj: Cell Reports, Vol 18, Iss 8, Pp 2045-2057 (2017)
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2017.01.076
Popis: 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.
Databáze: OpenAIRE
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