Dietary effects on A2AR expression in liver and adipose tissues: A role for A2AR in protecting against inflammation and insulin resistance in obesity
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Obesity causes a wide variety of metabolic diseases including fatty liver disease and diabetes. Mechanistically, obesityassociated 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 Gprotein coupled receptor families, adenosine 2A receptor (A2AR) is antinflammatory. However, little is known about nutritional regulation of A2AR as it relates to insulin resistance. In the present study, the expression of A2AR in liver and adipose tissue was examined in wild type (WT) C57BL/6J mice upon feeding a highfat diet (HFD) or a control lowfat diet (LFD). Also, both A2AR deficient mice and WT C57BL/6J mice were fed an HFD or LFD for 12 weeks to examine the involvement of A2AR in dietinduced 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 A2ARdeficient macrophages. Compared with LFDfed WT mice, HFDfed WT mice displayed obesity and obesityrelated inflammation in liver and adipose tissue and systemic insulin resistance. Interestingly, the levels of A2AR in both the liver and adipose tissue of HFDfed WT mice were increased significantly compared with LFDfed mice. When comparing with HFDfed WT mice, HFDfed A2ARdeficient mice displayed an significant increase in the severity of inflammation and insulin resistance. In cultured cells, the proinflammatory responses were much enhanced in A2ARdeficient macrophage in relative to WT cells regardless of palmitate treatment. Taken together, these results suggest that HFD feeding induces the expression of A2AR, which in turn exerts a defensive role in protecting against inflammation and insulin resistance.Support or Funding InformationThis study was support in part by NIH grants. Also, Dr. Wu is supported by an NIFA program.
