Effects of clofibrate on the human fat cell adenylate cyclase system.

The effects of chlofibrate on the adenylate cyclase system of human adipocytes were studied. Clofibrate reduced basal as well as hormone-NaF)stimulated adenylate cyclase activities to about the same extent (45% inhibition at 1 mg/ml clofibrate). The relative extent of hormonal stimulation was not altered by this compound. The inhibitory action of clofibrate was non-competitive with respect to the substrate ATP and cofactors (Mg2+-ions). Inhibition of enzyme activity was detectable after 2.5 min. Our results suggest that the antilipolytic activity of clofibrate is mediated via inhibition of the catalytic subunit of the fat cell adenylate cyclase.