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What is Hormone-Sensitive Lipase?

Shrinivas Kanade Apr 7, 2019
Hormone-sensitive lipase is an enzyme that acts on fatty acid esters of glycerol and takes part in biological activities. It was previously known as cholesteryl ester hydrolase (CEH). Learn more about it.
Hormone-Sensitive Lipase (HSL) is one of the lipases that are manufactured by the pancreas in the human body. They are enzymes that take active part in several biological activities. Their importance in inflammation, facilitating messaging between the body cells, coordination cell activities, and digestion is undeniable.
Different types of lipases like pancreatic, gastric, lingual, hepatic, lysosomal and phospholipases are involved in digesting food. They are made and released along with other enzymes and hormones by the pancreas into the stomach, and small intestine of the gastrointestinal tract to aid digestion. They act on food and convert complex foods into simple forms.
Our diet consists of lipids (fats), and the task of breaking these complex molecules to simple triglycerides which are fatty substances, is carried out by these enzymes, i.e., lipases.
These triglycerides are further acted upon by the different types of lipases to produce monoglycerides and diglycerides (fatty acids) to liberate free fatty acids. Free fatty acid molecules easily pass through the lining of the intestine to mix with the blood, and are transported to the different parts of the body to provide energy.

Role of HSL

Hormone-sensitive lipase is an intracellular neutral lipase that acts (hydrolyze) on different types of fatty acid esters of glycerol that are found in natural oils and fats. It has two forms in the human body: short and long. The long form is found in organs that are involved in the production of steroids such as testes. 
In testes, it acts on the cholesterol esters to produce free cholesterol, which is then used in the synthesis of steroid hormone. The short form is found in adipose tissues where it acts on the triglycerides to produce fatty acids. 
The breaking down of triglycerides is carried out in 3 stages:
  • As explained above in the first stage, HSL acts on a triglyceride molecule to produce a free fatty acid and a diglyceride molecule. To highlight its relation with its target, this lipase form is also called triglyceride lipase.
  • Lipase that acts on a diglyceride molecule in the second stage to produce two monoglyceride molecule is referred to as diglyceride lipase.
  • In the 3rd stage, monoglyceride lipase acts on a monoglyceride molecule to produce a free fatty acid molecule, which then runs amok and passes through the wall of the intestine into the blood.
The form of lipase that acts on the triglycerides initially is affected by hormones, and for this reason, is known as hormone-sensitive lipase. The rest of the two forms involved in the process elaborated above are very fast acting agents (10 to 100 times) than the HSL which functions as a rate limiting or speed-breaking enzyme of this chain of reactions.
It is known that a gene encoded by the name of LIPE is the master of lipase production in the body. An individual having a defective LIPE gene won't be able to maintain the required HSL levels (intracellular) or serum lipase levels, and is bound to suffer from lipase deficiency.
Triglycerides are stored mainly in adipose tissues in humans, including all mammals. To fulfill the energy requirements of the body and release free fatty acids in the plasma, they are acted upon. In normal conditions, the surface of droplets of lipid (in adipose tissue) is covered by the protein perilipins. The HSL resides in the cytoplasm of the same cell.
Chemically, this lipase does not have the ability to neutralize the perilipins, and the droplet is protected from it. This condition demands an external intervention which will let the HSL act on the droplet of lipid. 
The body satisfies this condition by releasing the protein kinase A (an enzyme) which carries out phosphorylation of perilipin and neutralizes it by adding phosphate group (PO4) to it.
At the same time, the release of protein kinase A also provides for activation of the HSL which after its phosphorylation proceeds to the hydrolysis of triglycerides. This releases free fatty acid which are the major source of energy in mammals.
There are some health conditions such as pancreas problems, Crohn's disease or cystic fibrosis in which the production of lipase is affected. On occasions, one also has to deal with the lowered lipase levels in pancreatitis. In such situations, the problem of how to increase the HSL is solved by ingesting lipase supplements.