Lipolysis

Lipolysis is the metabolic process of hydrolyzing triglycerides stored in adipose tissue and other lipid-rich tissues into glycerol and free fatty acids (FFAs). In adipose tissue, triglycerides are cleaved by a sequence of lipases: adipose triglyceride lipase (ATGL) initiates breakdown to diacylglycerol; hormone-sensitive lipase (HSL) converts diacylglycerol to monoacylglycerol; monoacylglycerol lipase (MGL) completes hydrolysis to glycerol and FFAs. Glycerol is released into the circulation and is used mainly by the liver for gluconeogenesis or glycerol metabolism, whereas FFAs are transported by albumin to other tissues for beta-oxidation and energy production.

Regulation is controlled by hormonal and nutritional state. Catecholamines activate beta-adrenergic receptors, raising intracellular cAMP and activating protein kinase A, which phosphorylates HSL and perilipin, promoting lipolysis. Insulin inhibits lipolysis by reducing cAMP production and suppressing HSL activity. Cortisol and growth hormone can promote lipolysis, especially during fasting or stress. The activity of ATGL is rate-limiting and coordinated with the lipid droplet surface through regulatory cofactors.

Physiological role and implications: lipolysis provides energy during fasting, prolonged exercise, and cold exposure; it also contributes to metabolic fuels in various tissues. Dysregulation of lipolysis is linked to metabolic diseases. In insulin resistance and obesity, elevated FFAs from increased lipolysis can contribute to ectopic fat deposition and impaired glucose metabolism. In lipodystrophy, adipose tissue dysfunction alters lipolysis and lipid storage.

Measurement and clinical aspects: plasma free fatty acids and glycerol are commonly used markers of peripheral lipolysis; therapies that modulate lipolysis are explored in metabolic disease contexts.