Hormone-sensitive lipase

Hormone-sensitive lipase (, HSL) also previously known as cholesteryl ester hydrolase (CEH) is an is_associated_with::enzyme that, in humans, is encoded by the LIPE is_associated_with::gene.

HSL is an intracellular neutral is_associated_with::lipase that is capable of hydrolyzing a variety of is_associated_with::esters. The enzyme has a long and a short form. The long form is expressed in steroidogenic tissues such as is_associated_with::testis, where it converts is_associated_with::cholesteryl esters to free is_associated_with::cholesterol for steroid hormone production. The short form is expressed in adipose tissue, among others, where it hydrolyzes stored is_associated_with::triglycerides to free is_associated_with::fatty acids.

Nomenclature
During fasting-state the increased free fatty acid secretion by is_associated_with::adipocyte cells was attributed to adrenaline hormone. Hence the name "hormone-sensitive lipase". Other hormones like is_associated_with::catecholamines and is_associated_with::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 is_associated_with::hydrolyze the first fatty acid from a is_associated_with::triacylglycerol molecule, freeing a is_associated_with::fatty acid and is_associated_with::diglyceride. It 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.

HSL is activated when the body needs to mobilize energy stores, and so responds positively to is_associated_with::catecholamines, is_associated_with::ACTH. It is inhibited by is_associated_with::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.

Another important role is the release of cholesterol from cholesterol esters for use in the production of is_associated_with::steroids.

Activation
It may be activated by two mechanisms.


 * In the first, phosphorylated is_associated_with::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 is_associated_with::cAMP-dependent protein kinase (PKA). This pathway is significantly less effective than the first, which is necessary for lipid mobilization in response to is_associated_with::cyclic AMP, which itself is provided by the activation of Gs protein-coupled receptors that promote cAMP production.  Examples include is_associated_with::beta adrenergic stimulation of the is_associated_with::glucagon receptor and is_associated_with::ACTH stimulation of the is_associated_with::ACTH receptor in the adrenal cortex.