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

in Journal of Endocrinology
Authors:
Ya Pei Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, USA

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Honggui Li Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, USA

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Yuli Cai Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, USA
Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China

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Jing Zhou Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, USA

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Xianjun Luo Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, USA

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Linqiang Ma Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, USA

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Kelly McDaniel Research, Central Texas Veterans Health Care System, Baylor Scott & White Digestive Disease Research Center, Baylor Scott & White Health, Department of Medical Physiology, Texas A&M University College of Medicine, Temple, Texas, USA

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Tianshu Zeng Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

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Yanming Chen Department of Endocrinology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

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Xiaoxian Qian Department of Cardiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

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Yuqing Huo Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA
Drug Discovery Center, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China

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Shannon Glaser Research, Central Texas Veterans Health Care System, Baylor Scott & White Digestive Disease Research Center, Baylor Scott & White Health, Department of Medical Physiology, Texas A&M University College of Medicine, Temple, Texas, USA

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Fanyin Meng Research, Central Texas Veterans Health Care System, Baylor Scott & White Digestive Disease Research Center, Baylor Scott & White Health, Department of Medical Physiology, Texas A&M University College of Medicine, Temple, Texas, USA

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Gianfranco Alpini Research, Central Texas Veterans Health Care System, Baylor Scott & White Digestive Disease Research Center, Baylor Scott & White Health, Department of Medical Physiology, Texas A&M University College of Medicine, Temple, Texas, USA

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Lulu Chen Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

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Chaodong Wu Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, USA

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Correspondence should be addressed to L Chen or C Wu: cheria_chen@126.com or cdwu@tamu.edu

*(Y Pei, H Li and Y Cai contributed equally to this work)

DOI:
https://doi.org/10.1530/JOE-18-0169
Volume/Issue:
Volume 239: Issue 3
Article Type:
Research Article
Page Range:
365–376
Online Publication Date:
Dec 2018
Copyright:
© 2018 Society for Endocrinology 2018
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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.

Supplementary Materials

    • Table 1 Primer sequences
    • Figure S1. Related to Figure 1. HFD feeding induces adipose tissue inflammation. Male C57BL/6J mice, at 5 - 6 weeks of age, were fed a high-fat diet (HFD) or low-fat diet (LFD) for 12 weeks. Additional age-matched male mice were maintained on a standard chow diet (CD). After the feeding period, mice were fasted for 4 hr before harvest. (A) Lysates of adipose tissue (epididymal fat) were examined for proinflammatory signaling using Western blot analysis. (B) Quantification of blots. Data are means ± SEM. n = 6 - 8. *, P < 0.05 and **, P < 0.01 HFD vs. LFD for the same protein; ††,
    • Figure S2. Related to Figure 3. Disruption of A2AR has limited effects on whole body energy expenditure. Male A2AR–/– mice and wild-type littermate A2AR+/+ mice, at 5 - 6 weeks of age, were fed a high-fat diet (HFD) for 12 weeks. After the feeding period, mice were subjected to the PromethionTM system to analyze energy metabolism. Energy expenditure was calculated based on respiratory quotient (RQ) and VO2. Dark bars, night time periods. Data are means + SEM. n = 4 - 6. *, P < 0.05 HFD-A2AR–/– vs. HFD-A2AR+/+.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© 2018 Society for Endocrinology 2018
Page(s):
12
Article Type:
Research Article
Received Date:
23 Aug 2018
Accepted Date:
17 Sep 2018
Print Publication Date:
01 Dec 2018
Online Publication Date:
Dec 2018
Keywords:
adenosine 2A receptor; obesity; adipose tissue inflammation; macrophage