Prostaglandin E2 (PGE2) is synthesized in adipose tissue and acts locally to inhibit lipolysis. This study examined PGE2 synthesis by presumptive and mature adipocytes isolated from lean and obese Zucker rats. Isoproterenol-stimulated lipolysis was greater in short-term incubations of mature adipocytes isolated from lean rats than in those from obese rats in terms of both sensitivity (lean 10(-7) M vs. obese 10(-6) M) and magnitude of response (five-fold greater in lean at 10(-6) M). Prostaglandin E2 synthesis was dose-dependent in isoproterenol-stimulated adipocytes from lean rats, while PGE2 synthesis in adipocytes from obese rats was not altered, regardless of treatment. Primary cell cultures of presumptive adipocytes from both phenotypes released PGE2 in response to lipolytic compounds, however, cultures from obese rats had lower PGE2 release rates than cultures from lean rats. In addition, compared to cultures derived from lean rats, a greater degree of adipocyte differentiation in cultures from obese rats was associated with lower basal PGE2 synthesis. These results suggest that an impairment in the ability of adipocytes isolated from obese Zucker rats to enzymatically synthesize PGE2 accompanies maturation.