A2B Adenosine receptors prevent insulin resistance by inhibiting adipose tissue inflammation via maintaining alternative macrophage activation

Balázs Csóka, Balázs Koscsó, Gábor Töro, Endre Kókai, L. Virag, Zoltán H. Németh, Pál Pacher, P. Bai, G. Haskó

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Obesity causes increased classical and decreased alternative macrophage activation, which in turn cause insulin resistance in target organs. Because A2B adenosine receptors (ARs) are important regulators of macrophage activation, we examined the role of A2B ARs in adipose tissue inflammation and insulin resistance. A2B AR 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 adipose tissue of A2B AR-deficient mice. Furthermore, in in vitro studies, we found that stimulation of A2B ARs 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 A2B ARs hold promise for preventing adipose tissue inflammation and insulin resistance.

Original languageEnglish
Pages (from-to)850-866
Number of pages17
JournalDiabetes
Volume63
Issue number3
DOIs
Publication statusPublished - Mar 2014

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Adenosine A2B Receptors
Macrophage Activation
Insulin Resistance
Adipose Tissue
Inflammation
CCAAT-Enhancer-Binding Proteins
Peroxisome Proliferator-Activated Receptors
Macrophages
Purinergic P1 Receptors
Adipokines
High Fat Diet
Lipid Metabolism
Nonesterified Fatty Acids
Interleukin-4
Transcription Factors
Obesity
Glucose

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

A2B Adenosine receptors prevent insulin resistance by inhibiting adipose tissue inflammation via maintaining alternative macrophage activation. / Csóka, Balázs; Koscsó, Balázs; Töro, Gábor; Kókai, Endre; Virag, L.; Németh, Zoltán H.; Pacher, Pál; Bai, P.; Haskó, G.

In: Diabetes, Vol. 63, No. 3, 03.2014, p. 850-866.

Research output: Contribution to journalArticle

Csóka, Balázs ; Koscsó, Balázs ; Töro, Gábor ; Kókai, Endre ; Virag, L. ; Németh, Zoltán H. ; Pacher, Pál ; Bai, P. ; Haskó, G. / A2B Adenosine receptors prevent insulin resistance by inhibiting adipose tissue inflammation via maintaining alternative macrophage activation. In: Diabetes. 2014 ; Vol. 63, No. 3. pp. 850-866.
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