Nicotinic acid: studies on the mechamism of its antilipolytic action.

Abstract

Nicotinic acid in vitro is known to depress basal lipolytic rates in adipose tissue and also to inhibit the action of a number of agents which stimulate adipose tissue lipolysis. Three possible mechanisms by which nicotinic acid could exert this antilipolytic effect have been examined. The rat epididymal fat pad was used as an adipose tissue source. In vitro nicotinic acid was found to have no effect on fat pad phosphodiesterase activity. Similarly, no direct effect of this drug on lipase activity could be demonstrated. Nicotinic acid in vitro was observed to inhibit, by about 50%, the increased lipolytic rates induced in isolated fat pad sections with theophylline. This inhibitory action, however, was antagonized by the further in vitro addition of the β-adrenergic blocking agent, nethalide, (pronethalol). Also, this antagonism appeared to be a direct one. It is suggested from these results that nicotinic acid does not exert its antilipolytic action by either increasing the degradation of cyclic 39,59-AMP or by inhibiting directly the activity of lipase. It would appear, however, that nicotinic acid acts at a site that is either identical with the receptor for nethalide or is closely associated to it. Thus, it seems possible that nicotinic acid may exert its antilipolytic action by depressing the production of cyclic 39,59-AMP.