POTENTIATION OF BETA-ADRENOCEPTOR AGONIST MEDIATED-LIPOLYSIS BY CHOLESTEROL-DERIVED OXYSTEROLS

Cholesterol-derived oxysterols such as cholestanol, cholestanone and c oprostanone were able to potentiate epinephrine-induced lipolysis in i ntact rat adipocytes but not cholesterol. The relative potency of the oxysterols followed the sequence: cholestanone greater than or equal t o coprostanone > cholestanol. Cholestanone was selected to study its m ode of action on epinephrine-induced lipolysis. A sustained increase i n the level of cAMP was observed in adipocytes incubated with both cho lestanone and epinephrine compared to a transient peaking of cAMP in a dipocytes incubated with epinephrine alone. Binding assays using [I-12 5]cyanopindolol (beta-adrenergic receptor antagonist) showed that chol estanone could increase the binding affinity of [I-125]-cyanopindolol to beta-adrenergic receptors on rat adipocyte ghost membranes without affecting the total number of binding sites. The results suggest that cholestanone exerts its potentiation effect by facilitating the bindin g of beta-adrenergic agonist to its receptor.