Attenuated adenosine R-site effect in adipocytes in obesity

Adenosine is a local hormone or a retaliatory metabolite that executes its effect via a plasma membrane receptor, the R-site. In human adipocytes it inhibits cyclic AMP accumulation and lipolysis. N6-(phenylisopropyl)adenosine is a nonmetabolizable derivative that is an R-site agonist not sharing other effects of the parent nucleoside. In subcutaneous abdominal fat cells from obese subjects (130% to 207% of ideal body weight, N = 8), the antilipolytic effect of N6-(phenylisopropyl) adenosine was markedly attenuated as compared to that in fat cells from normal weight subjects (83% to 121% of ideal body weight, N = 8). There was a negative correlation between the effectiveness of the nucleoside analog and the relative body weight of the donor. The effect of N6-(phenylisopropyl)adenosine on cyclic AMP accumulation was similarly attenuated. These findings may explain some of the metabolic alterations observed in obesity.