Fig. 4

Regulation of Lipid Droplet Formation by TG. The left panel of this figure depicts the multi-step synthesis of triglycerides (TAGs). Initially, glycerol-3-phosphate acyltransferase (GPAT) catalyzes the biosynthesis of lysophosphatidic acid (LPA) with a preference for saturated fatty acids and glycerol-3-phosphate (G3P) as substrates. GPATs exist in two forms, the mitochondrial isoform (GPAT1/2) and the endoplasmic isoform (GPAT3/4). Next, 1-acylglycerol-3-phosphate O-acyltransferases (AGPATs) convert LPA to phosphatidic acid (PA). Following this, the enzyme lipin, a magnesium-ion-dependent phosphatidic acid phosphohydrolase, dephosphorylates PA to yield diacylglycerol (DAG). Diacylglycerol O-acyltransferases (DGAT1/2) catalyze DAG and fatty acyl-CoA to TAG. The biogenesis of lipid droplets commences with TG synthesis, which accumulates between the ER membrane’s two leaflets. Proteins bound to the lipid droplet surface, such as perilipins (PLINs), localize to the phospholipid monolayer, while the neutral lipid core comprises triacylglycerols and sterol esters. The right panel illustrates the hydrolysis of TG. Adipose triglyceride lipase (ATGL), encoded by the PNPLA2 gene, initiates TAG degradation to produce DAG, which is subsequently hydrolyzed to monoacylglycerol (MAG) by hormone-sensitive lipase (LIPE). LIPE also participates in steroid hormone synthesis by converting cholesteryl esters to free cholesterol. Finally, monoglyceride lipase (MGLL) hydrolyzes MAG to free fatty acids and glycerol