Importance of TNFα and neutral lipases in human adipose tissue lipolysis

Catecholamines and natriuretic peptides stimulate human adipocyte lipolysis through an increase in cAMP and cGMP levels, resulting in phosphorylation and activation of hormone-sensitive lipase. A defect in hormone-sensitive lipase expression might contribute to the resistance to catecholamine-induced lipolysis observed in obesity. The respective roles and regulation of hormone-sensitive lipase and adipose triglyceride lipase in spontaneous and hormone-stimulated lipolysis remain to be determined. Tumor necrosis factor α stimulates triglyceride hydrolysis by multiple intracellular pathways acting on insulin signaling, G proteins and perilipins, and might contribute to enhanced plasma fatty acid levels in obesity. Characterization of the lipolytic pathways might provide novel strategies to decrease free fatty acid production and reverse insulin resistance and other obesity-related metabolic complications.