Molecular Pharmacology, Vol 7, 455-464, Copyright © 1971 by the American Society for Pharmacology and Experimental Therapeutics

Valinomycin as an Antilipolytic Agent

Effects on Cyclic 3',5'-Adenylic Acid, Adenyl Cyclase, Respiration, and Glucose Metabolism in Brown and White Fat Cells

¹ Division of Biological and Medical Sciences, Brown University, Providence, Rhode Island 02912

Valinomycin blocked the stimulation by catecholamines of lipolysis and the accumulation of both total and labeled cyclic AMP in brown and white fat cells. Under conditions when valinomycin blocked lipolysis produced by epinephrine, the ATP content of brown fat cells was not reduced. The lipolytic action of dibutyryl cyclic AMP was also blocked by valinomycin. The degradation of tritiated adenine to labeled water was stimulated by valinomycin. In white fat cell ghosts, catecholamine-stimulated adenyl cyclase activity was reduced 20% by valinomycin, and basal activity was enhanced. In white fat valinomycin inhibited both basal and insulin-stimulated conversion of glucose to carbon dioxide, lactate, and total lipids. In brown fat, however, basal glucose conversion to carbon dioxide was stimulated by valinomycin. Basal respiration in brown fat cells was doubled by valinomycin in both the presence and absence of either pyruvate or oxalacetate. The stimulation of respiration by octanoate was reduced 50% by valinomycin. These observations suggest that the antilipolytic action of valinomycin is the result of other factors in addition to the inhibition of adenyl cyclase.

Note:
ACKNOWLEDGMENTS The authors are indebted to Dudith W. Rosenthal for the ATP determinations.