Another hormone-sensitive triglyceride lipase in fat cells?

T mobilization of fatty acid from triglycerides and cholesterol esters provides the primary source of energy in mammals. Hormone-sensitive lipase (HSL) is a multifunctional tissue lipase that plays a critical role in this process. The enzyme has broad specificity, catalyzing the hydrolysis of tri-, di-, and monoacylglycerols, as well as cholesterol esters. HSL has been studied most extensively in adipose tissue, where it is thought to catalyze the major rate-limiting step in lipolysis. The lipase is acutely activated by cAMP-dependent phosphorylation, which also leads to its redistribution from the cytoplasm to the lipid droplet (1, 2) (Fig. 1). Regulation of adipocyte HSL is the primary means by which lipolytic agents, such as catecholamines, stimulate the release of free fatty acids (FFAs) and thus control circulating levels. Plasma FFAs profoundly influence carbohydrate and lipid utilization, storage, and synthesis, both in liver and muscle. Moreover, fatty acids produced in fat cells can uncouple ATP synthesis, resulting in adaptive thermogenesis (3). Products of fatty acid metabolism are also thought to bind directly to nuclear receptors, thus regulating transcription of genes involved in lipid synthesis and breakdown (4). These observations predict HSL to be an important player in controlling the balance of substrate utilization and storage. In addition to adipocytes, HSL is found in skeletal muscle, heart, brain, pancreatic beta cells, adrenal gland, ovaries, testes, and macrophages. Although triglyceride hydrolysis is probably also important in muscle and pancreas, cholesterol ester hydrolysis appears to play a separate biological role. In macrophages, HSL has been suggested to regulate foam cell formation (5). The presence of the enzyme in adrenal and reproductive tissues suggests a potential role in hormone-regulated steroidogenesis and possibly in sperm development, by regulating the availability of free cholesterol (6).