Abstract

The antilipolytic activity of the alpha-adrenergic agent clonidine was studied using fat cells from the epididymal fat bodies of golden hamsters. Lipolysis activated in a relatively dilute suspension of adipocytes (<30,000 cells/ml) with either 3-isobutyl-1-methylxanthine or isoproterenol was inhibited by clonidine. At cell densities >300,000 cells/ml, only 3-isobutyl-1-methylxanthine-accelerated lipolysis was inhibited by clonidine; isoproterenol-activated lipolysis was not. The antilipolytic activity of clonidine toward isoproterenol-activated lipolysis was also lost when adipocytes (<30,000 cells/ml) were incubated in media previously used for cell incubation. These findings suggested the appearance of a substance in the incubation medium which inhibited the antilipolytic activity of clonidine. The antilipolytic activity of clonidine was dramatically enhanced by addition of adenosine deaminase or theophylline to incubation media, suggesting that the substance is adenosine. Clonidine inhibited cyclic AMP accumulation to a greater extent in the presence of either adenosine deaminase or theophylline. The antilipolytic activity of prostaglandin E₁ and nicotinic acid, but not insulin, was also enhanced by the presence of adenosine deaminase. The release of adenosine from adipocytes in which the nucleotide pool was labeled by incubation with either [¹⁴C]- or [³H]adenine was readily detected after 5 min of incubation and was maximal after 30 min. From these data we conclude that the sensitivity of fat cells to the antilipolytic effects of clonidine, prostaglandin E₁, and nicotinic acid is strongly influenced by the presence of adenosine produced by the incubated cells and that optimal antilipolytic activity of these agents is seen only in the absence of adenosine.