Arginase inhibition ameliorates adipose tissue inflammation in mice with diet-induced obesity

Huan Hu, Jiyoung Moon, Ji Hyung Chung, Oh Yoen Kim, Rina Yu, Min-Jeong Shin

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Abstract This study examined whether oral administration of an arginase inhibitor regulates adipose tissue macrophage infiltration and inflammation in mice with high fat diet (HFD)-induced obesity. Male C57BL/6 mice (n=30) were randomly assigned to control (CTL, n=10), HFD only (n=10), and HFD with arginase inhibitor N<sup>ω</sup>-hydroxy-nor-l-arginine (HFD with nor-NOHA, n=10) groups. Plasma and mRNA levels of cytokines in epididymal adipose tissues (EAT), macrophage infiltration into EAT, and macrophage phenotype polarization were measured in the animals after 12 weeks. Additionally, the effects of nor-NOHA on adipose tissue macrophage infiltration and mRNA expression of cytokines were measured in co-cultured 3T3-L1 adipocytes and RAW 264.7 macrophages. Macrophage infiltration into the adipocytes was significantly suppressed by nor-NOHA treatment in adipocyte/macrophage co-culture system and mice with HFD-induced obesity. Pro-inflammatory cytokines, including monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), were significantly downregulated, and the anti-inflammatory cytokine IL-10 was significantly upregulated in nor-NOHA-treated co-cultured cells. In the mice with HFD-induced obesity, plasma and mRNA levels of MCP-1 significantly reduced after supplementation with nor-NOHA. In addition, oral supplement of nor-NOHA modified M1/M2 phenotype ratio in the EAT. Oral supplementation of an arginase inhibitor, nor-NOHA, altered M1/M2 macrophage phenotype and macrophage infiltration into HFD-induced obese adipose tissue, thereby improved adipose tissue inflammatory response. These results may indicate that arginase inhibition ameliorates obesity-induced adipose tissue inflammation.

Original languageEnglish
Article number34258
Pages (from-to)840-847
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume464
Issue number3
DOIs
Publication statusPublished - 2015 Jul 7

Keywords

  • Adipocytes
  • Arginase
  • Inflammation
  • Macrophage infiltration
  • Nor-NOHA

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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