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Macrophage ubiquitin-specific protease 2 modifies insulin sensitivity in obese mice.
Saito, Natsuko; Kimura, Shunsuke; Miyamoto, Tomomi; Fukushima, Sanae; Amagasa, Misato; Shimamoto, Yoshinori; Nishioka, Chieko; Okamoto, Shiki; Toda, Chitoku; Washio, Kohei; Asano, Atsushi; Miyoshi, Ichiro; Takahashi, Eiki; Kitamura, Hiroshi.
Affiliation
  • Saito N; Laboratory of Veterinary Physiology, Department of Veterinary Medicine, and Laboratory of Animal Therapeutics, Japan.
  • Kimura S; Laboratory of Histology and Cytology, Department of Functional Morphology, Graduate School of Medical Sciences, Hokkaido University, Kita15, Nishi7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan.
  • Miyamoto T; Department of Comparative and Experimental Medicine, Graduate School of Medicine, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan.
  • Fukushima S; Research Resources Center, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
  • Amagasa M; Laboratory of Veterinary Physiology, Department of Veterinary Medicine, and Laboratory of Animal Therapeutics, Japan.
  • Shimamoto Y; Department of Veterinary Science, Rakuno Gakuen University, 582 Midorimachi, Bunkyodai, Ebetsu, Hokkaido 069-8501, Japan.
  • Nishioka C; Research Resources Center, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
  • Okamoto S; Division of Endocrinology and Metabolism, National Institute for Physiological Sciences, 38 Nishigonaka Myodaiji, Okazaki, Aichi 444-8585, Japan.
  • Toda C; Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520-8063, USA.
  • Washio K; Laboratory of Veterinary Physiology, Department of Veterinary Medicine, and Laboratory of Animal Therapeutics, Japan.
  • Asano A; Laboratory of Laboratory Animal, Department of Basic Veterinary Science, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan.
  • Miyoshi I; Department of Comparative and Experimental Medicine, Graduate School of Medicine, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan.
  • Takahashi E; Research Resources Center, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
  • Kitamura H; Laboratory of Veterinary Physiology, Department of Veterinary Medicine, and Laboratory of Animal Therapeutics, Japan.
Biochem Biophys Rep ; 9: 322-329, 2017 Mar.
Article in En | MEDLINE | ID: mdl-28956020
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.
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Diagnostic_studies Language: En Journal: Biochem Biophys Rep Year: 2017 Document type: Article Affiliation country: Japan Country of publication: Netherlands

Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Diagnostic_studies Language: En Journal: Biochem Biophys Rep Year: 2017 Document type: Article Affiliation country: Japan Country of publication: Netherlands