Figure 3.

Lipolysis and Lipid Signaling

Lipid intermediates involved in cellular signaling are generated by anabolic and catabolic reactions in distinct cellular compartments. 1,2-DGs, the ligands of conventional and novel PKCs, are formed at the plasma membrane by PLC-mediated degradation of PIP2. This reaction also generates IP3, a signaling molecule, which leads to Ca²⁺ efflux from the ER. De novo synthesis of 1,2-DGs at the ER may also contribute to PKC activation. FAs are ligands for nuclear receptors. They are generated by de novo synthesis or hydrolysis of neutral lipids or phospholipids. 2-AG is an important MG involved in endocannabinoid signaling. It originates from membrane-associated phospholipid hydolysis by PLCs and the subsequent hydrolysis of DGs by DAGLs. The contribution of TG hydrolysis by ATGL and HSL to cellular 2-AG concentrations is not known. The 2-AG signal is inactivated by MGL. AGPAT, acyl-CoA acylglycerol-3-phosphate acyltransferase; 2-AG, 2-arachidonoyl-glycerol; ATGL, adipose triglyceride lipase; DAGL, diacylglycerol lipase; DG, diacylglycerol; 11, 2-DG, diacyl-sn1,2-glycerol, DGAT, acyl-CoA: diacylglycerol acyltransferase; FA, fatty acid; G, glycerol; G3P, glycerol-3-phosphate; GPAT, glycerol-3-phosphate acyltransferase; HSL, hormone-sensitive lipase; IP3, inositol-1,4,5-trisphosphate; LPA, lysophosphatidic acid; MG, monoacylglycerol; MGL, monoglyceride lipase; PA, phosphatidic acid; PAPase, PA phosphohydrolase; PIP2, phosphatidylinositol 4,5-bisphosphate; PKC, protein kinase C; PLC, phospholipase C; TG, triacylglycerol.