Macrophage ubiquitin-specific protease 2 modifies insulin sensitivity in obese mice
We previously reported that ubiquitin-specific protease (USP) 2 in macrophages down-regulates genes associated with metabolic diseases, suggesting a putative anti-diabetic role for USP2 in macrophages. In this study, we evaluate this role at both cellular and individual levels. Isolated macrophages...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-03-01
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| Series: | Biochemistry and Biophysics Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580817300328 |
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| author | Natsuko Saito Shunsuke Kimura Tomomi Miyamoto Sanae Fukushima Misato Amagasa Yoshinori Shimamoto Chieko Nishioka Shiki Okamoto Chitoku Toda Kohei Washio Atsushi Asano Ichiro Miyoshi Eiki Takahashi Hiroshi Kitamura |
| author_facet | Natsuko Saito Shunsuke Kimura Tomomi Miyamoto Sanae Fukushima Misato Amagasa Yoshinori Shimamoto Chieko Nishioka Shiki Okamoto Chitoku Toda Kohei Washio Atsushi Asano Ichiro Miyoshi Eiki Takahashi Hiroshi Kitamura |
| author_sort | Natsuko Saito |
| collection | DOAJ |
| description | We previously reported that ubiquitin-specific protease (USP) 2 in macrophages down-regulates genes associated with metabolic diseases, suggesting a putative anti-diabetic role for USP2 in macrophages. In this study, we evaluate this role at both cellular and individual levels. Isolated macrophages forcibly expressing Usp2a, a longer splicing variant of USP2, failed to modulate the insulin sensitivity of 3T3-L1 adipocytes. Similarly, macrophage-selective overexpression of Usp2a in mice (Usp2a transgenic mice) had a negligible effect on insulin sensitivity relative to wild type littermates following a three-month high-fat diet. However, Usp2a transgenic mice exhibited fewer M1 macrophages in their mesenteric adipose tissue. Following a six-month high-fat diet, Usp2a transgenic mice exhibited a retarded progression of insulin resistance in their skeletal muscle and liver, and an improvement in insulin sensitivity at an individual level. Although conditioned media from Usp2a-overexpressing macrophages did not directly affect the insulin sensitivity of C2C12 myotubes compared to media from control macrophages, they did increase the insulin sensitivity of C2C12 cells after subsequent conditioning with 3T3-L1 cells. These results indicate that macrophage USP2A hampers obesity-elicited insulin resistance via an adipocyte-dependent mechanism. |
| first_indexed | 2024-12-11T00:20:16Z |
| format | Article |
| id | doaj.art-f2bf2c95144646929de023d6521dbddb |
| institution | Directory Open Access Journal |
| issn | 2405-5808 |
| language | English |
| last_indexed | 2024-12-11T00:20:16Z |
| publishDate | 2017-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj.art-f2bf2c95144646929de023d6521dbddb2022-12-22T01:27:47ZengElsevierBiochemistry and Biophysics Reports2405-58082017-03-019C32232910.1016/j.bbrep.2017.01.009Macrophage ubiquitin-specific protease 2 modifies insulin sensitivity in obese miceNatsuko Saito0Shunsuke Kimura1Tomomi Miyamoto2Sanae Fukushima3Misato Amagasa4Yoshinori Shimamoto5Chieko Nishioka6Shiki Okamoto7Chitoku Toda8Kohei Washio9Atsushi Asano10Ichiro Miyoshi11Eiki Takahashi12Hiroshi Kitamura13Laboratory of Veterinary Physiology, Department of Veterinary Medicine, and Laboratory of Animal Therapeutics, JapanLaboratory of Histology and Cytology, Department of Functional Morphology, Graduate School of Medical Sciences, Hokkaido University, Kita15, Nishi7, Kita-ku, Sapporo, Hokkaido 060-8638, JapanDepartment of Comparative and Experimental Medicine, Graduate School of Medicine, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, JapanResearch Resources Center, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, JapanLaboratory of Veterinary Physiology, Department of Veterinary Medicine, and Laboratory of Animal Therapeutics, JapanDepartment of Veterinary Science, Rakuno Gakuen University, 582 Midorimachi, Bunkyodai, Ebetsu, Hokkaido 069-8501, JapanResearch Resources Center, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, JapanDivision of Endocrinology and Metabolism, National Institute for Physiological Sciences, 38 Nishigonaka Myodaiji, Okazaki, Aichi 444-8585, JapanDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520-8063, USALaboratory of Veterinary Physiology, Department of Veterinary Medicine, and Laboratory of Animal Therapeutics, JapanLaboratory of Laboratory Animal, Department of Basic Veterinary Science, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, JapanDepartment of Comparative and Experimental Medicine, Graduate School of Medicine, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, JapanResearch Resources Center, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, JapanLaboratory of Veterinary Physiology, Department of Veterinary Medicine, and Laboratory of Animal Therapeutics, JapanWe previously reported that ubiquitin-specific protease (USP) 2 in macrophages down-regulates genes associated with metabolic diseases, suggesting a putative anti-diabetic role for USP2 in macrophages. In this study, we evaluate this role at both cellular and individual levels. Isolated macrophages forcibly expressing Usp2a, a longer splicing variant of USP2, failed to modulate the insulin sensitivity of 3T3-L1 adipocytes. Similarly, macrophage-selective overexpression of Usp2a in mice (Usp2a transgenic mice) had a negligible effect on insulin sensitivity relative to wild type littermates following a three-month high-fat diet. However, Usp2a transgenic mice exhibited fewer M1 macrophages in their mesenteric adipose tissue. Following a six-month high-fat diet, Usp2a transgenic mice exhibited a retarded progression of insulin resistance in their skeletal muscle and liver, and an improvement in insulin sensitivity at an individual level. Although conditioned media from Usp2a-overexpressing macrophages did not directly affect the insulin sensitivity of C2C12 myotubes compared to media from control macrophages, they did increase the insulin sensitivity of C2C12 cells after subsequent conditioning with 3T3-L1 cells. These results indicate that macrophage USP2A hampers obesity-elicited insulin resistance via an adipocyte-dependent mechanism.http://www.sciencedirect.com/science/article/pii/S2405580817300328DiabetesObesityMacrophageInsulinUSP |
| spellingShingle | Natsuko Saito Shunsuke Kimura Tomomi Miyamoto Sanae Fukushima Misato Amagasa Yoshinori Shimamoto Chieko Nishioka Shiki Okamoto Chitoku Toda Kohei Washio Atsushi Asano Ichiro Miyoshi Eiki Takahashi Hiroshi Kitamura Macrophage ubiquitin-specific protease 2 modifies insulin sensitivity in obese mice Biochemistry and Biophysics Reports Diabetes Obesity Macrophage Insulin USP |
| title | Macrophage ubiquitin-specific protease 2 modifies insulin sensitivity in obese mice |
| title_full | Macrophage ubiquitin-specific protease 2 modifies insulin sensitivity in obese mice |
| title_fullStr | Macrophage ubiquitin-specific protease 2 modifies insulin sensitivity in obese mice |
| title_full_unstemmed | Macrophage ubiquitin-specific protease 2 modifies insulin sensitivity in obese mice |
| title_short | Macrophage ubiquitin-specific protease 2 modifies insulin sensitivity in obese mice |
| title_sort | macrophage ubiquitin specific protease 2 modifies insulin sensitivity in obese mice |
| topic | Diabetes Obesity Macrophage Insulin USP |
| url | http://www.sciencedirect.com/science/article/pii/S2405580817300328 |
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