Cyclic AMP metabolism and lipolysis in cultured human adipocyte precursors

Abstract

Triacylglycerol breakdown (lipolysis) results from a series of reactions culminated by activation of hormone-stimulated triacylglycerol lipase, an enzyme unique to adipose tissue. Components of the lipolytic process were studied in human omental adipocyte precursors differentiating in culture. The levels of cyclic[c]AMP, the 2nd messenger of lipolytic hormones, were about 6 times higher in fat cell precursors than those in abdominal skin fibroblasts. L-Isoproterenol resulted in significant elevation of cAMP levels in both cell types. Preincubation of intact adipocyte precursors with insulin resulted in significant enhancement of low Km cAMP phosphodiesterase activity; this hormone had no effect on fibroblast phosphodiesterase activity, a distinctive biochemical difference despite the morphological similarities between the 2 cell types during the early stages of adipocyte precursor maturation. Incubation of adipocyte precursors with isoproterenol resulted in the release of fatty acids into the medium, findings indicative of hormone-stimulated lipase activity and the operation of the entire lipolytic cascade; isoproterenol-stimulated lipolysis was inhibited by insulin. Release of fatty acids from fibroblasts was not observed. Hormone-stimulated lipolysis and insulin stimulation of cAMP phosphodiesterase activity are expressed during early stages of human adipocyte precursor differentiation.