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 consistently. Adipose tissue also produces PGI₂, but this eicosanoid has not had a demonstrated effect on lipolysis under physiological conditions previously. We investigated both PGE₂ and PGI₂ production and their effects on lipolysis in rat adipose tissue. We found that 1) EPI-stimulated PGE₂ production (like PGI₂ production) requires the cooperation of adipocytes and endothellal cells, 2) adipose tissue produces PGE₂ and PGI₂ at comparable rates, 3) indomethacin inhibits EPI-induced PGE₂ and PGI₂ 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) PGI₂ 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 antllipolytic effect of PGE₂ and the lipolytic effect of PGI₂ in isolated adipocytes in the absence of endothelial cells are comparable, 6) PGI₂ antagonizes the antllipolytic effect of PGE₂ in isolated adipocytes in the absence of endothelial cells in a dosage-related manner, and 7) the antllipolytic 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 antllipolytic agent, and PGI₂, a potent lipolytic agent. The failure of PGH synthase inhibition to affect lipolysis can be explained by concurrent PGE₂ and PGI₂ 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.