Macrophage ubiquitin-specific protease 2 modifies insulin sensitivity in obese mice

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

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)322-329
Number of pages8
JournalBiochemistry and Biophysics Reports
Publication statusPublished - Mar 1 2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry


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