Obesity causes increased classical and decreased alternative macrophage activation, which in turn cause insulin resistance in target organs. Because A2B adenosine receptors (AR)s are important regulators of macrophage activation, we examined the role of A2BARs in adipose tissue inflammation and insulin resistance. A2BAR deletion impaired glucose and lipid metabolism in mice fed chow but not a high fat diet, which was paralleled by dysregulation of the adipokine system and increased classical macrophage activation and inhibited alternative macrophage activation. The expression of alternative macrophage activation-specific transcriptions factors, including CCAAT/enhancer binding protein β, interferon regulatory factor 4, and peroxisome proliferator-activated receptor γ was decreased in A2BAR deficient mice. Furthermore, in in vitro studies, we found that stimulation of A2BARs suppressed free fatty acid-induced deleterious inflammatory and metabolic activation of macrophages. Moreover, AR activation upregulated the interleukin-4-induced expression of CCAAT/enhancer binding protein β, interferon regulatory factor 4, and peroxisome proliferator-activated receptor γ in macrophages. Altogether, our results indicate that therapeutic strategies targeting A2BARs hold promise for preventing adipose tissue inflammation and insulin resistance.
- Received April 10, 2013.
- Accepted October 31, 2013.
- © 2013 by the American Diabetes Association.
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