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[Biochemistry](https://durgical.com/en/biochemistry/) · Enzyme

# Hormone-sensitive lipase (HSL)

Hormone-sensitive lipase releases fatty acids from stored fat when the body needs energy (fasting, stress, exercise).

Updated 2026-11-01

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## Key facts

- In the adipocyte: mainly hydrolyses diacylglycerol to monoacylglycerol; ATGL makes the first cut of triacylglycerol.
- Glucagon and adrenaline activate it (β receptor, cAMP, PKA), phosphorylating it together with perilipin.
- Insulin switches it off: it activates phosphodiesterase, lowers cAMP and it is dephosphorylated.
- Fatty acids travel bound to albumin to liver and muscle; glycerol goes to the liver for gluconeogenesis.

**Also called**
LIPE

**EC number**
[3.1.1.79](https://www.enzyme-database.org/query.php?ec=3.1.1.79)

**Genes**
LIPE

**Structure (PDB)**
[8ZVQ](https://www.rcsb.org/structure/8ZVQ)

## Regulation

- Phosphorylation by PKA (adrenaline, glucagon, noradrenaline): activates.
- Insulin (phosphodiesterase 3B) and AMPK: inhibit.

## Inhibitors and toxins

- Insulin (physiological)
- Experimental HSL inhibitors

## Clinical notes

- Without insulin (type 1 diabetes) lipolysis runs free: many fatty acids reach the liver and ketones form.
- Loss-of-function LIPE variants cause partial lipodystrophy with insulin resistance.

## Pathways

- [Fatty acid β-oxidation](https://durgical.com/en/biochemistry/pathways/fatty-acid-oxidation/)

## Related conditions

- [Obesity](https://durgical.com/en/conditions/obesity/)
- [Type 2 diabetes mellitus](https://durgical.com/en/conditions/type-2-diabetes-mellitus/)
- [Diabetic ketoacidosis](https://durgical.com/en/conditions/diabetic-ketoacidosis/)

## Related

- [Palmitate (palmitic acid)](https://durgical.com/en/biochemistry/molecules/palmitate/)
- [Carnitine shuttle](https://durgical.com/en/biochemistry/topics/carnitine-shuttle/)
- [Carnitine palmitoyltransferase I (CPT-I)](https://durgical.com/en/biochemistry/enzymes/carnitine-palmitoyltransferase-i/)
- [Acetyl-CoA carboxylase (ACC)](https://durgical.com/en/biochemistry/enzymes/acetyl-coa-carboxylase/)

## Test yourself

Think of the answer, then tap the question to see it.

## Which hormones activate hormone-sensitive lipase?

Adrenaline, noradrenaline and glucagon, via cAMP and PKA.

## How does insulin slow lipolysis?

It activates phosphodiesterase 3B, cAMP falls and HSL is left dephosphorylated and inactive.

## What happens to the glycerol released by lipolysis?

It goes to the liver, where glycerol kinase phosphorylates it and it enters gluconeogenesis.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [LIPE: Hormone-sensitive lipase (human)](https://www.uniprot.org/uniprotkb/Q05469/entry) (UniProt, 2026); [Triglyceride catabolism](https://reactome.org/PathwayBrowser/#/R-HSA-163560) (Reactome, 2026); [8ZVQ: Cryo-EM Structure of Human Hormone-sensitive Lipase (HSL)](https://www.rcsb.org/structure/8ZVQ) (RCSB Protein Data Bank, 2026).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/biochemistry/enzymes/hormone-sensitive-lipase/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/enzymes/hormone-sensitive-lipase/