lipolisis

Lipolysis is the metabolic process by which stored triglycerides are hydrolyzed into glycerol and free fatty acids. In humans it occurs primarily in adipose tissue, where triglycerides stored in lipid droplets are mobilized to meet energy demands during fasting, prolonged exercise, or stress. The process is tightly regulated by hormonal signals and intracellular enzymes.

The first committed step is catalyzed by adipose triglyceride lipase (ATGL), aided by its coactivator CGI-58, which converts triglycerides to diacylglycerol and fatty acids. The next step is mediated mainly by hormone-sensitive lipase (HSL), which converts diacylglycerol to monoacylglycerol and fatty acids. Finally, monoglyceride lipase (MGL) hydrolyzes monoacylglycerol to glycerol and fatty acids. Perilipin, a protein coating the lipid droplet, modulates access of lipases; phosphorylation of perilipin by protein kinase A increases ATGL and HSL activity in response to catecholamines.

Regulation occurs through hormonal signaling. Catecholamines binding to beta-adrenergic receptors raise cyclic AMP and activate protein kinase A, promoting lipolysis. Insulin opposes lipolysis by lowering cAMP levels and activating phosphodiesterases, thereby deactivating lipases. Other hormones, including cortisol and growth hormone, can stimulate lipolysis, while various adipokines modulate the process.

The products are free fatty acids and glycerol. Free fatty acids bind albumin for transport to tissues where they undergo beta-oxidation for energy, while glycerol enters the liver for gluconeogenesis or glycolysis depending on metabolic state.

Clinical relevance includes metabolic regulation and disease associations. Dysregulated lipolysis is linked to obesity and type 2 diabetes, where elevated circulating free fatty acids contribute to insulin resistance; lipodystrophy and cachexia involve altered lipolysis. Pharmacological agents can influence lipolysis via adrenergic or insulin pathways.