Control of fat cell phosphohydrolase by lipolytic agents.

The Mg2+-dependent phosphatidate phosphohydrolase activity increased in the microsomal and decreased in the soluble fraction of isolated rat fat cells incubated for short periods with the lipolytic hormones or agents, epinephrine, cyclic AMP, theophylline, and dibutyryl cyclic AMP. Adrenocorticotropin, on the other hand, increased not only the microsomal but also the soluble activity. The increases in microsomal activity ranged from 30 to 134% with epinephrine to almost 200% with dibutyryl cyclic AMP. The decreases in soluble activity were more modest. The effect of epinephrine was inhibited by the beta-adrenergic antagonist propranolol while the alpha-antagonist phentolamine enhanced it. These results strongly suggest that the fat cell phosphatidate phosphohydrolase is controlled through the beta-adrenergic receptor and the activity of adenylate cyclase. Lipolysis, as measured by fatty acid release, was stimulated in a similar pattern as the microsomal activity suggesting parallel activation of the hormone sensitive lipase and phosphatidate phosphohydrolase. It is speculated that the activation of this lipogenic enzyme by lipolytic stimuli may represent a mechanism whereby fatty acid release from adipose tissue may be modulated and intracellular fatty acid accumulation may be counteracted during accelerated lipolysis in adipose tissue.