title: Role of A1and A2Aadenosine receptor agonists in adipose tissue inflammation induced by obesity in mice.
abstract: Adenosine receptors are expressed in adipose tissue and control physiological and pathological events such as lipolysis and inflammation. The aim of this study was to evaluate the activity of N6-cyclopentyladenosine (CPA), a potent and selective A1adenosine receptor agonist; 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxyamidoadenosine hydrochloride (CGS-21680), an A2Aadenosine receptor agonist; and 5'-N-ethylcarboxamidoadenosine (NECA), a potent non-selective adenosine receptor agonist on adipose tissue inflammatory alterations induced by obesity in mice. Swiss mice were fed with a high-fat diet for 12 weeks and agonists were administered in the last two weeks. Body weight, adiposity and glucose homeostasis were evaluated. Inflammation in adipose tissue was assessed by evaluation of adipokine production and macrophage infiltration. Adenosine receptor signaling in adipose tissue was also evaluated. Mice that received CGS21680 presented an improvement in glucose homeostasis in association with systemically reduced inflammatory markers (TNF-α, PAI-1) and in the visceral adipose tissue (TNF-α, MCP-1, macrophage infiltration). Activation of p38 signaling was found in adipose tissue of this group of mice. NECA-treated mice presented some improvements in glucose homeostasis associated with an observed weight loss. Mice that received CPA presented only a reduction in the ex vivo basal lipolysis rate measured within visceral adipose tissue. In conclusion, administration of the A2Areceptor agonist to obese mice resulted in improvements in glucose homeostasis and adipose tissue inflammation, corroborating the idea that new therapeutics to treat obesity could emerge from these compounds.
authors.affiliation: Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, Av. São Francisco de Assis 218, 12916-900 Bragança Paulista, SP, Brazil.
authors.forename: Caroline Candida
authors.initials: CC
authors.lastname: DeOliveira
authors.affiliation: Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, Av. São Francisco de Assis 218, 12916-900 Bragança Paulista, SP, Brazil.
authors.forename: Cintia Rabelo E
authors.initials: CR
authors.lastname: Paiva Caria
authors.affiliation: Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, Av. São Francisco de Assis 218, 12916-900 Bragança Paulista, SP, Brazil.
authors.forename: Erica Martins
authors.initials: EM
authors.lastname: Ferreira Gotardo
authors.affiliation: Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, Av. São Francisco de Assis 218, 12916-900 Bragança Paulista, SP, Brazil.
authors.forename: Marcelo Lima
authors.initials: ML
authors.lastname: Ribeiro
authors.affiliation: Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, Av. São Francisco de Assis 218, 12916-900 Bragança Paulista, SP, Brazil. Electronic address: alessandra.gambero@usf.edu.br.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gambero
mesh_terms: D058907:Adenosine A1 Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D007249:Inflammation / Q000150:complications; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D051379:Mice; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D043705:Receptor, Adenosine A2A / Q000378:metabolism*
chemical_list: D058907:Adenosine A1 Receptor Agonists; D058908:Adenosine A2 Receptor Agonists; D015415:Biomarkers; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D005947:Glucose
keywords: A(2A) adenosine receptor; Adipokine; CGS 21680; Macrophage; Obesity