Regulation of adipose tissue inflammation by adenosine 2A receptor in obese mice

Ya Pei, Honggui Li, Yuli Cai, Jing Zhou, Xianjun Luo, Linqiang Ma, Kelly McDaniel, Tianshu Zeng, Yanming Chen, Xiaoxian Qian, Yuqing Huo, Shannon Glaser, Fanyin Meng, Gianfranco Alpini, Lulu Chen, Chaodong Wu

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Adenosine 2A receptor (A2AR) exerts anti-inflammatory effects. However, the role of A2AR in obesity-associated adipose tissue inflammation remains to be elucidated. The present study examined the expression of A2AR in adipose tissue of mice with diet-induced obesity and determined the effect of A2AR disruption on the status of obesity-associated adipose tissue inflammation. WT C57BL/6J mice and A2AR-disrupted mice were fed a high-fat diet (HFD) for 12 weeks to induce obesity and adipose tissue inflammation. In vitro, bone marrow-derived macrophages from A2AR-disrupted mice and WT control mice were treated with palmitate and examined for macrophage proinflammatory activation. Compared with that of low-fat diet (LFD)-fed WT mice, A2AR expression in adipose tissue of HFD-fed WT mice was increased significantly and was present predominantly in adipose tissue macrophages. The increase in adipose tissue A2AR expression in HFD-fed mice was accompanied with increased phosphorylation states of c-Jun N-terminal kinase 1 p46 and nuclear factor kappa B p65 and mRNA levels of interleukin (Il)-1beta, Il6 and tumor necrosis factor alpha. In A2AR-disrupted mice, HFD feeding induced significant increases in adipose tissue inflammation, indicated by enhanced proinflammatory signaling and increased proinflammatory cytokine expression, and adipose tissue insulin resistance, indicated by a decrease in insulin-stimulated Akt phosphorylation relative to those in WT mice. Lastly, A2AR disruption enhanced palmitate-induced macrophage proinflammatory activation. Taken together, these results suggest that A2AR plays a protective role in obesity-associated adipose tissue inflammation, which is attributable to, in large part, A2AR suppression of macrophage proinflammatory activation.

Original languageEnglish (US)
Pages (from-to)365-376
Number of pages12
JournalJournal of Endocrinology
Volume239
Issue number3
DOIs
StatePublished - Dec 1 2018

Keywords

  • Adenosine 2A receptor
  • Adipose tissue inflammation
  • Macrophage
  • Obesity

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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  • Cite this

    Pei, Y., Li, H., Cai, Y., Zhou, J., Luo, X., Ma, L., McDaniel, K., Zeng, T., Chen, Y., Qian, X., Huo, Y., Glaser, S., Meng, F., Alpini, G., Chen, L., & Wu, C. (2018). Regulation of adipose tissue inflammation by adenosine 2A receptor in obese mice. Journal of Endocrinology, 239(3), 365-376. https://doi.org/10.1530/JOE-18-0169