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Dietary effects on A 2A R expression in liver and adipose tissues: A role for A 2A R in protecting against inflammation and insulin resistance in obesity
Author(s) -
Pei Ya,
Cai Yuli,
Li Honggui,
Woo ShihLung,
Liu Mengyang,
Huo Yuqing,
Wu Chaodong
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.644.24
Subject(s) - insulin resistance , medicine , endocrinology , adipose tissue , inflammation , fatty liver , type 2 diabetes , obesity , insulin , biology , insulin receptor , diabetes mellitus , chemistry , disease
Obesity causes a wide variety of metabolic diseases including fatty liver disease and diabetes. Mechanistically, obesity‐associated inflammation has been implicated as a key factor in the development of fat deposition, insulin resistance, and metabolic dysregulation. However, the regulation of inflammation in obesity remains to be explored. As a member of the G‐protein coupled receptor families, adenosine 2A receptor (A 2A R) is ant‐inflammatory. However, little is known about nutritional regulation of A 2A R as it relates to insulin resistance. In the present study, the expression of A 2A R in liver and adipose tissue was examined in wild type (WT) C57BL/6J mice upon feeding a high‐fat diet (HFD) or a control low‐fat diet (LFD). Also, both A 2A R ‐deficient mice and WT C57BL/6J mice were fed an HFD or LFD for 12 weeks to examine the involvement of A 2A R in diet‐induced inflammation and insulin resistance. Lastly, the effects of major macronutrients, i.e., glucose and palmitate, on the inflammatory responses were examined in both WT and A 2A R‐deficient macrophages. Compared with LFD‐fed WT mice, HFD‐fed WT mice displayed obesity and obesity‐related inflammation in liver and adipose tissue and systemic insulin resistance. Interestingly, the levels of A 2A R in both the liver and adipose tissue of HFD‐fed WT mice were increased significantly compared with LFD‐fed mice. When comparing with HFD‐fed WT mice, HFD‐fed A2AR‐deficient mice displayed an significant increase in the severity of inflammation and insulin resistance. In cultured cells, the proinflammatory responses were much enhanced in A 2A R‐deficient macrophage in relative to WT cells regardless of palmitate treatment. Taken together, these results suggest that HFD feeding induces the expression of A 2A R, which in turn exerts a defensive role in protecting against inflammation and insulin resistance. Support or Funding Information This study was support in part by NIH grants. Also, Dr. Wu is supported by an NIFA program.