The resurgence of Hormone-Sensitive Lipase (HSL) in mammalian lipolysis.
The ability to store energy in the form of energy-dense triacylglycerol and to mobilize these stores rapidly during periods of low carbohydrate availability or throughout the strong metabolic demand is a highly conserved process, absolutely essential for survival. In the industrialized world the regulation of this pathway is viewed as an important therapeutic target for disease prevention. Adipose tissue lipolysis is a catabolic process leading to the breakdown of triacylglycerols stored in fat cells, and release of fatty acids and glycerol. Mobilization of adipose tissue fat is mediated by the MGL, HSL and ATGL, similarly functioning enzymes. ATGL initiates lipolysis followed by the actions of HSL on diacylglycerol, and MGL on monoacylglycerol. HSL is regulated by reversible phosphorylation on five critical residues. Phosphorylation alone, however, is not enough to activate HSL. Probably, conformational alterations and a translocation from the cytoplasm to lipid droplets are also involved. In accordance, Perilipin functions as a master regulator of lipolysis, protecting or exposing the triacylglycerol core of a lipid droplet to lipases. The prototype processes of hormonal lipolytic control are the β-adrenergic stimulation and suppression by insulin, both of which affect cytoplasmic cyclic AMP levels. Lipolysis in adipocytes is an important process in the management of body energy reserves. Its deregulation may contribute to the symptoms of type 2 diabetes mellitus and other pathological situations. We, herein, discuss the metabolic regulation and function of lipases mediating mammalian lipolysis with a focus on HSL, quoting newly identified members of the lipolytic proteome.
Department of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Panepistimiopolis, Zografou, 157 84 Athens, Greece.
Antonis D
AD
Lampidonis
Emmanuel
E
Rogdakis
Gerassimos E
GE
Voutsinas
Dimitrios J
DJ
Stravopodis
D000273:Adipose Tissue / Q000201:enzymology* / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D005223:Fats / Q000378:metabolism; D006801:Humans; D008066:Lipolysis; D008954:Models, Biological; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D002787:Sterol Esterase / Q000235:genetics / Q000378:metabolism*
D005223:Fats; D002787:Sterol Esterase