P-selectin glycoprotein ligand-1 deficiency is protective against obesity-related insulin resistance

Chikage Sato, Kenichi Shikata, Daisho Hirota, Motofumi Sasaki, Shingo Nishishita, Satoshi Miyamoto, Ryo Kodera, Daisuke Ogawa, Atsuhito Tone, Hitomi Usui Kataoka, Jun Wada, Nobuo Kajitani, Hirofumi Makino

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

OBJECTIVE: An inflammatory process is involved in the mechanism of obesity-related insulin resistance. Recent studies indicate that monocyte chemoattractant protein-1 (MCP-1) is a major chemokine that promotes monocyte infiltration into adipose tissues; however, the adhesion pathway in adipose tissues remains unclear. We aimed to clarify the adhesion molecules that mediate monocyte infiltration into adipose tissue. RESEARCH DESIGN AND METHODS: We used a DNA microarray to compare the gene expression profiles in epididymal white adipose tissues (eWAT) between db/db mice and C57/BL6 mice each fed a high-fat diet (HFD) or a low-fat diet (LFD). We investigated the change of insulin resistance and inflammation in eWAT in P-selectin glycoprotein ligand-1 (PSGL-1) homozygous knockout (PSGL-1-/-) mice compared with wild-type (WT) mice fed HFD. RESULTS: DNA microarray analysis revealed that PSGL-1, a major ligand for selectins, is upregulated in eWAT from both db/db mice and WT mice fed HFD. Quantitative real-time RT-PCR and immunohistochemistry showed that PSGL-1 is expressed on both endothelial cells and macrophages in eWAT of obese mice. PSGL-1-/- mice fed HFD showed a remarkable reduction of macrophage accumulation and expression of proinflammatory genes, including MCP-1 in eWAT. Moreover, adipocyte hypertrophy, insulin resistance, lipid metabolism, and hepatic fatty change were improved in PSGL-1-/- mice compared with WT mice fed HFD. CONCLUSIONS: These results indicate that PSGL-1 is a crucial adhesion molecule for the recruitment of monocytes into adipose tissues in obese mice, making it a candidate for a novel therapeutic target for the prevention of obesity-related insulin resistance.

Original languageEnglish
Pages (from-to)189-199
Number of pages11
JournalDiabetes
Volume60
Issue number1
DOIs
Publication statusPublished - Jan 1 2011

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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