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Hormone-sensitive lipase (EC3.1.1.79, HSL), also previously known as cholesteryl ester hydrolase (CEH),[5] is an enzyme that, in humans, is encoded by the LIPEgene.[6]
HSL is an intracellular neutral lipase that is capable of hydrolyzing a variety of esters.[7] The enzyme has a long and a short form. The long form is expressed in steroidogenic tissues such as testis, where it converts cholesteryl esters to free cholesterol for steroid hormone production. The short form is expressed in adipose tissue, among others, where it hydrolyzes stored triglycerides to free fatty acids.[8]
Nomenclature
During fasting-state the increased free fatty acid secretion by adipocyte cells was attributed to the hormone epinephrine, hence the name "hormone-sensitive lipase".[9] Other catecholamines and adrenocorticotropic hormone (ACTH) can also stimulate such responses. Such enzymatic action plays a key role in providing major source of energy for most cells.
Function
The main function of hormone-sensitive lipase is to mobilize the stored fats. Mobilization and Cellular Uptake of Stored Fats (with Animation) HSL functions to hydrolyze either a fatty acid from a triacylglycerol molecule, freeing a fatty acid and diglyceride, or a fatty acid from a diacylglycerol molecule, freeing a fatty acid and monoglyceride. Another enzyme found in adipose tissue, Adipose Triglyceride Lipase (ATGP), has a higher affinity for triglycerides than HSL, and ATGP predominately acts as the enzyme for triglyceride hydrolysis in the adipocyte. HSL is also known as triglyceride lipase, while the enzyme that cleaves the second fatty acid in the triglyceride is known as diglyceride lipase, and the third enzyme that cleaves the final fatty acid is called monoglyceride lipase. Only the initial enzyme is affected by hormones, hence its hormone-sensitive lipase name. The diglyceride and monoglyceride enzymes are tens to hundreds of times faster, hence HSL is the rate-limiting step in cleaving fatty acids from the triglyceride molecule.[10][11]
HSL is activated when the body needs to mobilize energy stores, and so responds positively to catecholamines, ACTH. It is inhibited by insulin. Previously, glucagon was thought to activate HSL, however the removal of insulin's inhibitory effects ("cutting the brakes") is the source of activation. The lipolytic effect of glucagon in adipose tissue is minimal in humans.[citation needed]
Another important role is the release of cholesterol from cholesteryl esters for use in the production of steroids[12] and cholesterol efflux.[13] Activity of HSL is important in preventing or ameliorating the generation of foam cells in atherosclerosis.[13]
In the first, phosphorylated perilipin A causes it to move to the surface of the lipid droplet, where it may begin hydrolyzing the lipid droplet.
Also, it may be activated by a cAMP-dependent protein kinase (PKA). This pathway is significantly less effective than the first, which is necessary for lipid mobilization in response to cyclic AMP, which itself is provided by the activation of Gs protein-coupled receptors that promote cAMP production. Examples include beta adrenergic stimulation, stimulation of the glucagon receptor and ACTH stimulation of the ACTH receptor in the adrenal cortex.
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Aten RF, Kolodecik TR, Macdonald GJ, Behrman HR (November 1995). "Modulation of cholesteryl ester hydrolase messenger ribonucleic acid levels, protein levels, and activity in the rat corpus luteum". Biol. Reprod. 53 (5): 1110–7. doi:10.1095/biolreprod53.5.1110. PMID8527515.
