Lipolysis pathways

Lipolysis pathways refer to the regulated hydrolysis of triacylglycerols (TAGs) stored in adipocyte lipid droplets into glycerol and free fatty acids (FFAs), primarily mediated by sequential action of three enzymes: adipose triglyceride lipase (ATGL/PNPLA2) for the initial TAG-to-diacylglycerol step, hormone-sensitive lipase (HSL) for diacylglycerol hydrolysis, and monoacylglycerol lipase (MGL) for final glycerol release.[1][3][7] This process is hormonally controlled, with catecholamines binding β-adrenergic receptors to activate adenylyl cyclase, elevate cAMP, and trigger protein kinase A (PKA) phosphorylation of perilipin (PLIN1) and HSL, enabling lipase translocation to lipid droplets and co-activation by CGI-58 (ABHD5).[1][3][4] Dysregulation contributes to metabolic disorders: excessive lipolysis drives FFAs release fueling insulin resistance and hepatic steatosis in obesity/type 2 diabetes, while impaired lipolysis promotes lipid accumulation in fatty liver disease; in cancer, it supports tumor proliferation via FFA supply or cachexia.[2][4][6] Although not a single therapeutic target, pathway components like ATGL, HSL, and regulators (e.g., β3-ARs, ABHD5) are explored for modulation—agonists for obesity/thermogenesis, inhibitors for hyperlipolysis—with challenges including FLD risk from lipase knockout.[4] Overall, balanced lipolysis is critical for energy homeostasis, PPAR signaling, and thermogenesis in brown adipose tissue.[3][4]

Other names

Adipocyte lipolysistriglyceride hydrolysis pathwayneutral lipid hydrolysis pathway

Activation of cAMP/PKA pathway via β-adrenergic receptors leading to phosphorylation of perilipin (PLIN1), HSL, and release of CGI-58 to activate ATGL; direct HSL phosphorylation and translocation to lipid droplets; inhibition of phosphodiesterase to sustain cAMP; disruption of ABHD5-PLIN1 interaction