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

Abstract

Adenosine 2A receptor (A 2A R) exerts anti-inflammatory effects. However, the role of A 2A R in obesity-associated adipose tissue inflammation remains to be elucidated. The present study examined the expression of A 2A R in adipose tissue of mice with diet-induced obesity and determined the effect of A 2A R disruption on the status of obesity-associated adipose tissue inflammation. WT C57BL/6J mice and A 2A R-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 A 2A R-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, A 2A R 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 A 2A R 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 A 2A R-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, A 2A R disruption enhanced palmitate-induced macrophage proinflammatory activation. Taken together, these results suggest that A 2A R plays a protective role in obesity-associated adipose tissue inflammation, which is attributable to, in large part, A 2A R 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

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Obese Mice
Purinergic P1 Receptors
Adipose Tissue
Inflammation
High Fat Diet
Obesity
Macrophage Activation
Palmitates
Macrophages
Mitogen-Activated Protein Kinase 8
Phosphorylation
Adenosine A2A Receptors
Fat-Restricted Diet
NF-kappa B
Interleukin-1beta
Inbred C57BL Mouse
Insulin Resistance
Anti-Inflammatory Agents
Tumor Necrosis Factor-alpha
Insulin

Keywords

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

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Pei, Y., Li, H., Cai, Y., Zhou, J., Luo, X., Ma, 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

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

In: Journal of Endocrinology, Vol. 239, No. 3, 01.12.2018, p. 365-376.

Research output: Contribution to journalArticle

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, vol. 239, no. 3, pp. 365-376. https://doi.org/10.1530/JOE-18-0169
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. / Regulation of adipose tissue inflammation by adenosine 2A receptor in obese mice. In: Journal of Endocrinology. 2018 ; Vol. 239, No. 3. pp. 365-376.
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AU - Zhou, Jing

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AU - Ma, Linqiang

AU - McDaniel, Kelly

AU - Zeng, Tianshu

AU - Chen, Yanming

AU - Qian, Xiaoxian

AU - Huo, Yuqing

AU - Glaser, Shannon

AU - Meng, Fanyin

AU - Alpini, Gianfranco

AU - Chen, Lulu

AU - Wu, Chaodong

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N2 - Adenosine 2A receptor (A 2A R) exerts anti-inflammatory effects. However, the role of A 2A R in obesity-associated adipose tissue inflammation remains to be elucidated. The present study examined the expression of A 2A R in adipose tissue of mice with diet-induced obesity and determined the effect of A 2A R disruption on the status of obesity-associated adipose tissue inflammation. WT C57BL/6J mice and A 2A R-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 A 2A R-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, A 2A R 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 A 2A R 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 A 2A R-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, A 2A R disruption enhanced palmitate-induced macrophage proinflammatory activation. Taken together, these results suggest that A 2A R plays a protective role in obesity-associated adipose tissue inflammation, which is attributable to, in large part, A 2A R suppression of macrophage proinflammatory activation.

AB - Adenosine 2A receptor (A 2A R) exerts anti-inflammatory effects. However, the role of A 2A R in obesity-associated adipose tissue inflammation remains to be elucidated. The present study examined the expression of A 2A R in adipose tissue of mice with diet-induced obesity and determined the effect of A 2A R disruption on the status of obesity-associated adipose tissue inflammation. WT C57BL/6J mice and A 2A R-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 A 2A R-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, A 2A R 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 A 2A R 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 A 2A R-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, A 2A R disruption enhanced palmitate-induced macrophage proinflammatory activation. Taken together, these results suggest that A 2A R plays a protective role in obesity-associated adipose tissue inflammation, which is attributable to, in large part, A 2A R suppression of macrophage proinflammatory activation.

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