hormone-sensitive lipase

During fasting-state the increased free fatty acid secretion by adipocyte cells was attributed to the hormone epinephrine, hence the name "hormone-sensitive lipase".{{cite journal | vauthors = Kraemer FB, Shen WJ | title = Hormone-sensitive lipase: control of intracellular tri-(di-)acylglycerol and cholesteryl ester hydrolysis | journal = Journal of Lipid Research | volume = 43 | issue = 10 | pages = 1585–94 | date = October 2002 | pmid = 12364542 | doi = 10.1194/jlr.R200009-JLR200 | doi-access = free }} 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.

Extracellular hormones, such as glucagon, epinephrine, thyroid-stimulating hormone, or adrenocorticotropic hormone (ACTH), bind to their respective G protein–coupled receptors (GPCR). When a GPCR is activated by its extracellular ligand, a conformational change is induced in the receptor that is transmitted to an attached intracellular heterotrimeric G protein complex by protein domain dynamics. The Gs alpha subunit of the stimulated G protein complex exchanges GDP for GTP in a reaction catalyzed by the GPCR and is released from the complex. The activated Gs alpha subunit binds to and activates an enzyme called adenylyl cyclase, which, in turn, catalyzes the conversion of ATP into cyclic AMP (cAMP). cAMP binds to and activates protein kinase A (PKA). It is PKA, activated by a hormone-induced signal transduction cascade, that phosphorylates and activates hormone sensitive lipase (HSL), hence the name. In addition to phosphorylating HSL, PKA phosphorylates perilipins on the surface of lipid droplets within adipose cells. This triggers them to "spread out" and allow for HSL to enter the lipid droplet. {{cite book | vauthors = Cox M, Nelson DR, Lehninger AL | title = Lehninger principles of biochemistry | publisher = W.H. Freeman | location = San Francisco | year = 2005 | isbn = 0-7167-4339-6 | url = https://archive.org/details/lehningerprincip00lehn_0 | url-access = registration }}

Activation of partially purified HSL requires Mg²⁺, ATP, and cyclic AMP.{{cite journal | vauthors = Khoo JC, Aquino AA, Steinberg D | title = The mechanism of activation of hormone-sensitive lipase in human adipose tissue | journal = The Journal of Clinical Investigation | volume = 53 | issue = 4 | pages = 1124–31 | date = April 1974 | pmid = 4360857 | pmc = 333098 | doi = 10.1172/JCI107650 }} Activation can be blocked when Ser552 is not phosphorylated because Ser554 is phosphorylated and when the dephosphorylation of Ser552 causes insulin to the insulin receptor, causing inhibition of lipolysis and stimulation of glucose transport.

Hormone stimulation of lipolysis in humans is similar to rats.

The main function of hormone-sensitive lipase is to mobilize stored fats.{{cite web | vauthors = Mehta S | title = Mobilization and Cellular Uptake of Stored Fats (Triacylglycerols) with Animation | work = Animations, Biochemistry Animations, Biochemistry Notes | publisher = PharmaXChange.info | date = October 2013 | url = http://pharmaxchange.info/press/2013/10/mobilization-and-cellular-uptake-of-stored-fats-triacylglycerols-with-animation/ | access-date = 2020-04-02 }} 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. This process allows energy metabolism in mammals.{{cite book |doi=10.1016/B978-0-08-091283-7.00110-7 |chapter=Ester Hydrolysis |title=Comprehensive Natural Products Chemistry |year=1999 | vauthors = Quinn DM, Medhekar R, Baker NR |pages=101–137 |isbn=978-0-08-091283-7 }} Although HSL is able to catalyze hydrolysis of triglycerides and diglycerides, another enzyme found in adipose tissue, adipose triglyceride lipase (ATGL), has a higher affinity for triglycerides than HSL, and ATGL predominantly acts as the enzyme for triglyceride-specific hydrolysis in the adipocyte. Hormone-sensitive lipase, which has 11-fold greater affinity for diglycerides than triglycerides, predominantly cleaves these diglycerides, forming 2-monoglyceride and a free fatty acid.{{cite journal | vauthors = Crabtree B, Newsholme EA | title = The activities of lipases and carnitine palmitoyltransferase in muscles from vertebrates and invertebrates | journal = The Biochemical Journal | volume = 130 | issue = 3 | pages = 697–705 | date = December 1972 | pmid = 4664927 | pmc = 1174508 | doi = 10.1042/bj1300697 }}{{cite journal | author = de Meijer J | title = Hormone sensitive lipase: structure, function and regulation | publisher = demeijer.com | date = 1998-05-01 | url = http://demeijer.com/biology/scriptie.pdf | access-date = 2009-02-04 }}

HSL is activated when the body needs to mobilize energy stores, and so responds positively to catecholamines and ACTH. It is inhibited by insulin.{{Cite web |title=Hormone Sensitive Lipase - an overview {{!}} ScienceDirect Topics |url=https://www.sciencedirect.com/topics/medicine-and-dentistry/hormone-sensitive-lipase |access-date=2025-04-14 |website=www.sciencedirect.com}}

Another important role is the release of cholesterol from cholesteryl esters for use in the production of steroids{{cite journal | vauthors = Kraemer FB | title = Adrenal cholesterol utilization | journal = Molecular and Cellular Endocrinology | volume = 265-266 | pages = 42–5 | date = February 2007 | pmid = 17208360 | doi = 10.1016/j.mce.2006.12.001 | s2cid = 35354595 }} and cholesterol efflux.{{cite journal | vauthors = Ouimet M, Marcel YL | title = Regulation of lipid droplet cholesterol efflux from macrophage foam cells | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 32 | issue = 3 | pages = 575–81 | date = March 2012 | pmid = 22207731 | doi = 10.1161/ATVBAHA.111.240705 | doi-access = free }} Activity of HSL is important in preventing or ameliorating the generation of foam cells in atherosclerosis.

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• {{cite journal | vauthors = Kraemer FB, Shen WJ | title = Hormone-sensitive lipase: control of intracellular tri-(di-)acylglycerol and cholesteryl ester hydrolysis | journal = Journal of Lipid Research | volume = 43 | issue = 10 | pages = 1585–94 | date = October 2002 | pmid = 12364542 | doi = 10.1194/jlr.R200009-JLR200 | doi-access = free }}
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• {{cite journal | vauthors = Anthonsen MW, Rönnstrand L, Wernstedt C, Degerman E, Holm C | title = Identification of novel phosphorylation sites in hormone-sensitive lipase that are phosphorylated in response to isoproterenol and govern activation properties in vitro | journal = The Journal of Biological Chemistry | volume = 273 | issue = 1 | pages = 215–21 | date = January 1998 | pmid = 9417067 | doi = 10.1074/jbc.273.1.215 | doi-access = free }}
• {{cite journal | vauthors = Shen WJ, Sridhar K, Bernlohr DA, Kraemer FB | title = Interaction of rat hormone-sensitive lipase with adipocyte lipid-binding protein | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 10 | pages = 5528–32 | date = May 1999 | pmid = 10318917 | pmc = 21893 | doi = 10.1073/pnas.96.10.5528 | bibcode = 1999PNAS...96.5528S | doi-access = free }}
• {{cite journal | vauthors = Syu LJ, Saltiel AR | title = Lipotransin: a novel docking protein for hormone-sensitive lipase | journal = Molecular Cell | volume = 4 | issue = 1 | pages = 109–15 | date = July 1999 | pmid = 10445032 | doi = 10.1016/S1097-2765(00)80192-6 | doi-access = free }}
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• {{cite journal | vauthors = Johnson WJ, Jang SY, Bernard DW | title = Hormone sensitive lipase mRNA in both monocyte and macrophage forms of the human THP-1 cell line | journal = Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology | volume = 126 | issue = 4 | pages = 543–52 | date = August 2000 | pmid = 11026666 | doi = 10.1016/S0305-0491(00)00220-0 }}
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• {{cite journal | vauthors = Smih F, Rouet P, Lucas S, Mairal A, Sengenes C, Lafontan M, Vaulont S, Casado M, Langin D | display-authors = 6 | title = Transcriptional regulation of adipocyte hormone-sensitive lipase by glucose | journal = Diabetes | volume = 51 | issue = 2 | pages = 293–300 | date = February 2002 | pmid = 11812735 | doi = 10.2337/diabetes.51.2.293 | doi-access = free }}
• {{cite journal | vauthors = Mairal A, Melaine N, Laurell H, Grober J, Holst LS, Guillaudeux T, Holm C, Jégou B, Langin D | display-authors = 6 | title = Characterization of a novel testicular form of human hormone-sensitive lipase | journal = Biochemical and Biophysical Research Communications | volume = 291 | issue = 2 | pages = 286–90 | date = February 2002 | pmid = 11846402 | doi = 10.1006/bbrc.2002.6427 }}
• {{cite journal | vauthors = Ylitalo K, Nuotio I, Viikari J, Auwerx J, Vidal H, Taskinen MR | title = C3, hormone-sensitive lipase, and peroxisome proliferator-activated receptor gamma expression in adipose tissue of familial combined hyperlipidemia patients | journal = Metabolism | volume = 51 | issue = 5 | pages = 664–70 | date = May 2002 | pmid = 11979403 | doi = 10.1053/meta.2002.32032 }}

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• {{MeshName|Hormone-Sensitive+Lipase}}

{{Esterases}}

Category:EC 3.1.1