COORDINATE CONTROL OF LIPOLYSIS BY PROSTAGLANDIN-E2 AND PROSTACYCLIN IN RAT ADIPOSE-TISSUE

PGE2 is a potent antilipolytic agent produced by adipose tissue, but its role as a physiological regulator of triglyceride lipolysis is controversial because inhibitors of prostaglandin synthesis have not enhanced hormone-stimulated lipolysis in adipose tissue consists. Adipose tissue also produces PGl2, but this eicosanoid has not had a demonstrated effect on lipolysis under physiological conditions previously. We investigated both PGE2 and PGl2 production and their effects on lipolysis in rat adipose tissue. We found that 1) EPI-stimulated PGE2 production (like PGl2 production) requires the cooperation of adipocytes and endothelial cells, 2) adipose tissue produces PGE2 and PGl2 at comparable rates, 3) indomethacin inhibits EPI-induced PGE2 and PGl2 production and has no effect on EPI-stimulated lipolysis when added to a mixture of adipocytes and endothelial cells or to intact epididymal fat pads, 4) PGl2 is a potent lipolytic agent when added to isolated adipocytes in the absence of endothelial cells under physiological conditions, 5) the magnitudes and the ED50s of the antilipolytic effect of PGE2 and the lipolytic effect of PGl2 in isolated adipocytes in the absence of endothelial cells are comparable, 6) PGl2 antagonizes the antilipolytic effect of PGE2 in isolated adipocytes in the absence of endothelial cells in a dosage-related manner, and 7) the antilipolytic effect of added PGE2 in isolated adipocytes is greater in the absence of endothelial cells than in their presence, suggesting that endogenous eicosanoid production reduces the effectiveness of added PGE2. These studies demonstrate that catecholamine-induced lipolysis is under the coordinate control of PGE2, a potent antilipolytic agent, and PGl2, a potent lipolytic agent. The failure of PGH synthase inhibition to affect lipolysis can be explained by concurrent PGE2 and PGl2 inhibition. The existence of this mechanism for coordinate control of lipolysis may have broad implications for the function of adipose tissue in health and disease.