Potentiation of beta-adrenoceptor agonist mediated-lipolysis by cholesterol-derived oxysterols.

Cholesterol-derived oxysterols such as cholestanol, cholestanone and coprostanone were able to potentiate epinephrine-induced lipolysis in intact rat adipocytes but not cholesterol. The relative potency of the oxysterols followed the sequence: cholestanone > or = coprostanone > cholestanol. Cholestanone was selected to study its mode of action on epinephrine-induced lipolysis. A sustained increase in the level of cAMP was observed in adipocytes incubated with both cholestanone and epinephrine compared to a transient peaking of cAMP in adipocytes incubated with epinephrine alone. Binding assays using [125I]cyanopindolol (beta-adrenergic receptor antagonist) showed that cholestanone could increase the binding affinity of [125I]-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 binding of beta-adrenergic agonist to its receptor.