Hormone-sensitive lipase

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AliasesLIPE, AOMS4, FPLD6, HSL, LHS, lipase E, hormone sensitive type, REH
External IDsOMIM: 151750 MGI: 96790 HomoloGene: 3912 GeneCards: LIPE
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 19: 42.4 – 42.43 MbChr 7: 25.08 – 25.1 Mb
PubMed search[3][4]
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Hormone-sensitive lipase (HSL) N-terminus

Hormone-sensitive lipase (EC, HSL), also previously known as cholesteryl ester hydrolase (CEH),[5] sometimes referred to as triacylglycerol lipase, is an enzyme that, in humans, is encoded by the LIPE gene.[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]


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.


The main function of hormone-sensitive lipase is to mobilize the stored fats .[10] 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.[11] 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 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.[12][13]

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[14] and cholesterol efflux.[15] Activity of HSL is important in preventing or ameliorating the generation of foam cells in atherosclerosis.[15]


It may be activated by two mechanisms.[16]

  • 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.
  • Activation of partially purified HSL requires Mg2e, ATP, and cyclic AMP.[17] 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.[11]
    • Hormone stimulation of lipolysis in humans is similar to rats.[17]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000079435 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000003123 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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". Biology of Reproduction. 53 (5): 1110–7. doi:10.1095/biolreprod53.5.1110. PMID 8527515.
  6. ^ Langin D, Laurell H, Holst LS, Belfrage P, Holm C (June 1993). "Gene organization and primary structure of human hormone-sensitive lipase: possible significance of a sequence homology with a lipase of Moraxella TA144, an antarctic bacterium". Proceedings of the National Academy of Sciences of the United States of America. 90 (11): 4897–901. Bibcode:1993PNAS...90.4897L. doi:10.1073/pnas.90.11.4897. PMC 46620. PMID 8506334.
  7. ^ Kraemer FB, Shen WJ (October 2002). "Hormone-sensitive lipase: control of intracellular tri-(di-)acylglycerol and cholesteryl ester hydrolysis". Journal of Lipid Research. 43 (10): 1585–94. doi:10.1194/jlr.R200009-JLR200. PMID 12364542.
  8. ^ "Entrez Gene: LIPE lipase, hormone-sensitive".
  9. ^ Kraemer FB, Shen WJ (October 2002). "Hormone-sensitive lipase: control of intracellular tri-(di-)acylglycerol and cholesteryl ester hydrolysis". Journal of Lipid Research. 43 (10): 1585–94. doi:10.1194/jlr.R200009-JLR200. PMID 12364542.
  10. ^ Mehta S (October 2013). "Mobilization and Cellular Uptake of Stored Fats (Triacylglycerols) with Animation". Animations, Biochemistry Animations, Biochemistry Notes. PharmaXChange.info. Retrieved 2020-04-02.
  11. ^ a b Quinn DM, Medhekar R, Baker NR (1999). "Ester Hydrolysis". Comprehensive Natural Products Chemistry. pp. 101–137. doi:10.1016/B978-0-08-091283-7.00110-7. ISBN 978-0-08-091283-7.
  12. ^ Crabtree B, Newsholme EA (December 1972). "The activities of lipases and carnitine palmitoyltransferase in muscles from vertebrates and invertebrates". The Biochemical Journal. 130 (3): 697–705. doi:10.1042/bj1300697. PMC 1174508. PMID 4664927.
  13. ^ de Meijer J (1998-05-01). "Hormone sensitive lipase: structure, function and regulation" (PDF). demeijer.com. Retrieved 2009-02-04. {{cite journal}}: Cite journal requires |journal= (help)
  14. ^ Kraemer FB (February 2007). "Adrenal cholesterol utilization". Molecular and Cellular Endocrinology. 265–266: 42–5. doi:10.1016/j.mce.2006.12.001. PMID 17208360. S2CID 35354595.
  15. ^ a b Ouimet M, Marcel YL (March 2012). "Regulation of lipid droplet cholesterol efflux from macrophage foam cells". Arteriosclerosis, Thrombosis, and Vascular Biology. 32 (3): 575–81. doi:10.1161/ATVBAHA.111.240705. PMID 22207731.
  16. ^ Cox M, Nelson DR, Lehninger AL (2005). Lehninger principles of biochemistry. San Francisco: W.H. Freeman. ISBN 0-7167-4339-6.
  17. ^ a b Khoo JC, Aquino AA, Steinberg D (April 1974). "The mechanism of activation of hormone-sensitive lipase in human adipose tissue". The Journal of Clinical Investigation. 53 (4): 1124–31. doi:10.1172/JCI107650. PMC 333098. PMID 4360857.

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