What is lipolysis

Due to popularity of injection lipolysis procedure, I’m often asked a question: “What is Lipolysis?”. It’s a pretty straightforward procedure with quite a complicated mechanism of action. So, if you are really interested to find out how lipolysis works and what exactly it is, arm yourself with patience.


Lipolysis is a metabolic process in which triacylglycerol (TAGs) are hydrolyzed and broken down into their constituent molecules: glycerol and free fatty acids (FFAs). Adipose TAGs store fat in the body, which is used for heat, energy, and insulation. During abstinence from food, the body uses fat storage as its primary source of energy, sparing protein. Overall, fats are the body’s most vital fuel, and the length of time a person can go without eating is mostly determined by the quantity of fat stored in adipose tissue. As a result, lipolysis is especially crucial when the body is in a fasting condition and blood glucose levels are low. It can also happen in non-stimulated situations (basal conditions).

Gluconeogenesis in the liver uses the glycerol produced by lipolysis as a source of carbon. FFAs are carried through the bloodstream coupled to albumin, where they are either oxidized in tissues or transformed to ketone bodies through a process known as beta-oxidation. Gluconeogenesis is aided by beta-oxidation byproducts such as Adenosine triphosphate (ATP), the major energy currency of the cell nd NADH. FFAs are converted to ketone bodies in the liver, which serves as an energy source for the brain, reducing additional blood glucose consumption. FFAs are used for producing energy and biosynthetic pathways throughout the body, except in white adipose tissue (WAT), where they are stored. When the body is deprived of nutrition, WAT releases FFAs and glycerol to replenish non-adipose tissues in a metabolic “fasting” state. Adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), and monoglyceride lipase are the three main enzymes involved in lipolysis.


Synthesis of Triacylglycerol

TAGs are acquired from the diet or generated endogenously, primarily in the liver, to provide the body with a considerable source of energy. Lipoproteins move them through the bloodstream and store them in adipose tissue. High-density lipoprotein (HDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), and chylomicrons are the key blood lipoproteins involved. Chylomicrons are made in the small intestine and carry dietary TAGs from there to tissues like muscle and adipose tissue.

Triacylglycerol Hydrolysis

During times of energy deprivation, WAT is stimulated to move toward higher net rates of lipolysis via homeostatic control. This compensatory mechanism is elucidated by a change in nutritional condition, which is governed by hormonal and physiological cues. Lipolysis takes place in a controlled and organized manner, with distinct enzymes working at each stage. Lipolysis is primarily triggered by catecholamines, although it is also influenced by other hormones and nutritional substances.


Non-adipose tissues with defective lipolysis lose their normal function, resulting in excessive TAG accumulation and lipid storage disorder. In non-adipose tissues, an excess of FFAs due to uncontrolled lipolysis results in lipotoxicity conversely. Chronic increase of circulating FFAs due to failure to package FFAs into lipid droplets can lead to chronic inflammation, mitochondrial malfunction, and cell death.


Fatty acids are transported in the blood via albumin. Fatty acids are oxidized for energy in tissues including muscle and kidney. Fatty acids are converted to ketone bodies in the liver, which are then oxidized by tissues including muscle and kidney. The brain uses ketone bodies for energy during a famine (fasting that lasts three or more days). Fuel is provided by ketone substances, acetoacetate, and -hydroxybutyrate. Glycerol is used by the liver as a carbon source for gluconeogenesis, which creates glucose for organs such as the brain and red blood cells.


Synthesis of Triacylglycerol

They’re made from FFAs created as a consequence of lipoprotein lipase’s action on chylomicrons and VLDL, as well as a glycerol moiety derived from glucose. Glycerol-3-phosphate (G3P) provides the glycerol moiety in the liver and adipose tissue. Because it contains the enzyme glycerol kinase, the liver can convert glycerol to G3P either indirectly or directly. Adipose cells lack this enzyme and must rely on an intermediary to create G3P. Insulin promotes the storage of TAGs in adipose tissue by stimulating the secretion of lipoprotein lipase and the uptake of glucose, which is converted to glycerol (through a DHAP intermediate) for triacylglycerol synthesis. Glucose is converted to DHAP, which is then decreased by NADH to create G3P. Phosphatidic acid is formed when G3P interacts with two fatty acyl CoA molecules. The phosphate group is broken down into a diacylglycerol, which then combines with some other fatty acyl CoA to generate a triacylglycerol.

Hydrolysis of triacylglycerol

As previously indicated, hormonal and physiological signals trigger WAT to accelerate lipolysis during times of energy deprivation. Lipolysis takes place in a controlled and organized manner, with distinct enzymes working at each stage. ATGL, HSL, and MGL are the three primary enzymes involved in lipolysis, according to the current model. Fasting-induced lipolysis is primarily triggered by catecholamines, mainly norepinephrine, while other hormones also play a role. Cortisol, glucagon, growth hormone (GH), and adrenocorticotropic hormone are among them (ACTH).

Caffeine and calcium, for example, are dietary substances that promote lipolysis. Each of these chemicals attaches to and acts on its membrane-bound receptors, triggering a signaling cascade involving cyclic AMP, a common second messenger. Protein kinase A is then activated when cyclic AMP binds to it (PKA). PKA phosphorylates HSL, the most crucial of the three enzymes involved in beginning lipolysis since it is enzymatically activated at all stages of hydrolysis, once it is enzymatically active. ATGL is responsible for the initial phase of TAG hydrolysis, which results in the formation of diacylglycerols and FAs. CGI-58 and G0S2 are two accessory proteins that modulate their function. ATGL hydrolase activity is coactivated by CGI-58, while ATGL hydrolase activity is inactivated by G0S2. The second step is performed by HSL, which hydrolyzes DAGs to produce monoacylglycerols and FAs. MGL is an MG-selective enzyme that produces glycerol and the third FA.

Metabolism of Fatty Acids

Fatty acids with short and medium chains freely permeate into the cytosol and mitochondria of cells. Fatty acid translocase (FAT) or fatty acid-binding protein (FABP)-mediated transport of long-chain fatty acids across the cell membrane into the cytosol is required (FABP). The fatty acids are then converted to fatty acyl-CoA by acyl-CoA synthase. Carnitine palmitoyltransferase-I (CPT-I) transports the fatty acyl-CoA into the mitochondria through the outer mitochondrial membrane, where it is converted to fatty acyl-carnitine. Carnitine acyl-translocase (CAT) transports the fatty acyl-carnitine over the inner membrane into the mitochondrial matrix, where it is converted back to fatty acyl-CoA by palmitoyltransferase-II (CPT-II) and ready for oxidation.

Beta Oxidation

The destruction of fatty acids by eliminating two carbons at a time is known as Beta oxidation. It occurs in the mitochondrial matrix of tissues such as the liver, muscle, and adipose tissue and is the major pathway for fatty acid catabolism. NADH, FADH, and Acetyl CoA are produced as two-carbon fragments are removed from the carboxyl end of the fatty acyl-CoA, resulting in NADH, FADH, and Acetyl CoA, which is used in the TCA cycle to create ATP. Fatty acids with an odd number of carbons produce one mole of propionyl-CoA, which is metabolized to succinyl-CoA and used in the TCA cycle. The principal regulator of movement through the pyruvate dehydrogenase (PDH) complex, beta-oxidation is also significant. PDH activity reduces when fatty acid oxidation rates are high, limiting glycolysis. This is important because patients with a fatty acid oxidation shortage have a compensatory increase in glucose oxidation and defective gluconeogenesis.

Synthesis of ketone

During regular eating and physiological states, ketone levels are low. The heart and skeletal muscles employ them to keep the little glucose available for the brain and erythrocytes. Fatty acids are converted to acetyl CoA in the liver during fasting, which then transforms into the ketone molecules acetoacetate and beta-hydroxybutyrate. These high amounts of ketones also block PDH activity and fatty acid oxidation, allowing glucose to be conserved and ketones to enter the brain as energy sources. During a fast, muscle metabolizes ketone bodies at the same rate as the liver, preventing them from accumulating in the blood. Ketoacidosis, which is more common in patients with, type I diabetes and necessitates constant monitoring, can occur if ketones in the blood rise to a certain level.


There are various methods for estimating lipolysis now in use, which is divided into two categories: non-activity-based approaches and activity-based methods. The quantity of the related enzymes and regulatory proteins is determined using non-activity-based approaches. The activity-based techniques entail directly measuring the activity of the enzymes in question.

Over the last few years, fresh and updated knowledge has been available, and lipolysis perspectives have shifted. The measurement of mRNA or protein expression utilized in non-activity-based approaches is now proven to be insufficient for estimating lipolysis capacity. It is vital to use a variety of techniques.


Obesity is frequently linked to changes in lipolysis. Higher basal rates of lipolysis, which might also stimulate the growth of insulin resistance, as well as decreased response to induced lipolysis, are among these alterations. Insulin resistance is promoted by the release of cytokines and lipid metabolites as a result of the combination of increased lipolysis and decreased lipogenesis. Furthermore, insulin-resistant people’s adipose tissue lacks the proteins necessary for mitochondrial activity. Mitochondrial-derived energy sources have a role in adipose tissue lipogenesis.

Obesity is characterized by an overabundance of WAT caused by adipocyte hypertrophy as a consequence of enhanced TAG accumulation. Obesity has become a global health problem due to its links to a variety of diseases, including type II diabetes, atherosclerosis, insulin resistance, and hypertension.


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