Regulation of adipose tissue inflammation by adenosine 2A receptor in obese mice. Academic Article uri icon

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.

published proceedings

  • J Endocrinol

altmetric score

  • 2.5

author list (cited authors)

  • Pei, Y. a., Li, H., Cai, Y., Zhou, J., Luo, X., Ma, L., ... Wu, C

citation count

  • 13

complete list of authors

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

publication date

  • December 2018