ER Stress Protein CHOP Mediates Insulin Resistance by Modulating Adipose Tissue Macrophage Polarity
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 an...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-02-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717301468 |
| _version_ | 1818139938847195136 |
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| author | Toru Suzuki Junhong Gao Yasushi Ishigaki Keiichi Kondo Shojiro Sawada Tomohito Izumi Kenji Uno Keizo Kaneko Sohei Tsukita Kei Takahashi Atsuko Asao Naoto Ishii Junta Imai Tetsuya Yamada Seiichi Oyadomari Hideki Katagiri |
| author_facet | Toru Suzuki Junhong Gao Yasushi Ishigaki Keiichi Kondo Shojiro Sawada Tomohito Izumi Kenji Uno Keizo Kaneko Sohei Tsukita Kei Takahashi Atsuko Asao Naoto Ishii Junta Imai Tetsuya Yamada Seiichi Oyadomari Hideki Katagiri |
| author_sort | Toru Suzuki |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-11T10:36:03Z |
| format | Article |
| id | doaj.art-bba53f47e339435f905712858ccfc4b1 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T10:36:03Z |
| publishDate | 2017-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-bba53f47e339435f905712858ccfc4b12022-12-22T01:10:42ZengElsevierCell Reports2211-12472017-02-011882045205710.1016/j.celrep.2017.01.076ER Stress Protein CHOP Mediates Insulin Resistance by Modulating Adipose Tissue Macrophage PolarityToru Suzuki0Junhong Gao1Yasushi Ishigaki2Keiichi Kondo3Shojiro Sawada4Tomohito Izumi5Kenji Uno6Keizo Kaneko7Sohei Tsukita8Kei Takahashi9Atsuko Asao10Naoto Ishii11Junta Imai12Tetsuya Yamada13Seiichi Oyadomari14Hideki Katagiri15Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, JapanDepartment of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, JapanDivision of Diabetes and Metabolism, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate 020-8505, JapanDepartment of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, JapanDepartment of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, JapanDepartment of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, JapanDepartment of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, JapanDepartment of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, JapanDepartment of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, JapanDepartment of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, JapanDepartment of Microbiology and Immunology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, JapanDepartment of Microbiology and Immunology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, JapanDepartment of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, JapanDepartment of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, JapanDivision of Molecular Biology, Institute for Genome Research, University of Tokushima, 3-18-15 Kuramoto, Tokushima 770-8503, JapanDepartment of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, JapanObesity 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.http://www.sciencedirect.com/science/article/pii/S2211124717301468ER stressadipose tissue macrophagemacrophage polarizationinsulin resistanceM2 macrophage |
| spellingShingle | Toru Suzuki Junhong Gao Yasushi Ishigaki Keiichi Kondo Shojiro Sawada Tomohito Izumi Kenji Uno Keizo Kaneko Sohei Tsukita Kei Takahashi Atsuko Asao Naoto Ishii Junta Imai Tetsuya Yamada Seiichi Oyadomari Hideki Katagiri ER Stress Protein CHOP Mediates Insulin Resistance by Modulating Adipose Tissue Macrophage Polarity Cell Reports ER stress adipose tissue macrophage macrophage polarization insulin resistance M2 macrophage |
| title | ER Stress Protein CHOP Mediates Insulin Resistance by Modulating Adipose Tissue Macrophage Polarity |
| title_full | ER Stress Protein CHOP Mediates Insulin Resistance by Modulating Adipose Tissue Macrophage Polarity |
| title_fullStr | ER Stress Protein CHOP Mediates Insulin Resistance by Modulating Adipose Tissue Macrophage Polarity |
| title_full_unstemmed | ER Stress Protein CHOP Mediates Insulin Resistance by Modulating Adipose Tissue Macrophage Polarity |
| title_short | ER Stress Protein CHOP Mediates Insulin Resistance by Modulating Adipose Tissue Macrophage Polarity |
| title_sort | er stress protein chop mediates insulin resistance by modulating adipose tissue macrophage polarity |
| topic | ER stress adipose tissue macrophage macrophage polarization insulin resistance M2 macrophage |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717301468 |
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