Lipids and their metabolism

Last updated: August 17, 2023

Summarytoggle arrow icon

After ingested fats (lipids) are cleaved by enzymes, lipids are absorbed in the small intestine and transported via the lymphatic system into the bloodstream. During this transport process, lipids are bound to special hydrophilic apolipoproteins. These lipoproteins control fat metabolism and have different proportions of bound fat as well as different functions. Elevated low-density lipoprotein (LDL) and triglycerides are associated with an increased risk of atherosclerosis; however, an increase in high-density lipoprotein (HDL) has a positive effect on the vessels. Treatment of elevated lipid levels usually involves the administration of lipid‑lowering agents (e.g., statins). Lifestyle changes also play an important role.

Overviewtoggle arrow icon


Lipid metabolism

Digestion and absorption of lipidstoggle arrow icon

Lipid digestion

Acyl-CoA and acetyl-CoA should not be confused with each other. Acyl-CoA is a collective name for all activated fatty acids. Acetyl-CoA is the acyl-CoA of acetic acid (also known as acetate).

There is a very small amount of lipid in the stool of healthy individuals. Defects in lipid digestion result in steatorrhea (i.e., fatty stool).

Enzymes in lipid digestion

Lipases are enzymes that catalyze the breakdown of fats into glycerol and fatty acids.

Enzyme Site Function
Lingual lipase
Gastric lipase
Pancreatic lipase

Lipid resorption

The decomposition products of lipid digestion form mixed micelles with bile acids.

Lipid transporttoggle arrow icon

Lipoproteins [1]

Abnormalities in the structure or metabolism of lipoproteins increase the risk of atherosclerosis.

Overview of lipoproteins
Lipoproteins (in order of descending density) Composition Function Apolipoproteins
High-density lipoprotein (HDL)
  • ApoE
  • ApoA-I
  • ApoC-II
Low-density lipoprotein (LDL)
Intermediate-density lipoprotein (IDL)
Very low-density lipoprotein (VLDL)

The lipoproteins in order of increasing triglycerides are HDL, LDL, IDL, VLDL, and chylomicrons.

Free fatty acids in the blood are not transported by lipoproteins but are instead bound to albumin.

HDL is Healthy (protective against atherosclerosis) and LDL is Lethal (cholesterol plaque formation in peripheral arteries increases risk of cardiac disease and stroke).


Overview of apolipoproteins
Apolipoprotein Function Component of
Apo E
  • Mediates remnant uptake by the liver
  • All except for LDL
Apo A-I
Apo C-II
Apo B Apo B-48
Apo B-100
  • Mediates endocytosis of LDL by binding to LDL receptors on hepatic and extrahepatic tissues
  • Particles originating from the liver

Particles originating from the LIVer: LDL, IDL, VLDL.

A-I is Activates LCAT and is only present on Alpha-lipoproteins (only HDL)

Two Cs of apolipoprotein C-II (two) function: Catalyzes Cleavage.

Enzymes in lipid transport

Enzyme Site Function
Hepatic lipase
  • Released by the liver and activated in the bloodstream
Hormone-sensitive lipase
  • Intracellular [2]
Lecithin-cholesterol acyltransferase (LCAT)
  • Found on the surface of HDL (synthesized by the liver)
Lipoprotein lipase (LPL)
Cholesteryl ester transfer protein
  • Synthesized by the liver, secreted into the blood stream

Lipoprotein lipase is activated by binding to its cofactor apo C-II.

Fatty acid metabolismtoggle arrow icon

Fatty acids and triacylglycerols (TAGs) are important energy carriers. They are stored in the adipose tissue and can be mobilized from there if necessary and degraded (via beta oxidation) while releasing energy in the form of ATP. TAGs are the storage form of fatty acids in the body. They consist of one molecule of glycerine esterified with three fatty acids. TAG metabolism is subject to strict regulation by the hormone-sensitive lipase of adipose tissue.

Fatty acids


  • Carboxylic acid with an unbranched chain of carbon atoms differing in length (from 1–24 carbon atoms)
  • Typically found as esters, including:
  • Degradation via beta oxidation releases energy in the form of ATP

An increased concentration of triglycerides in the blood is called hypertriglyceridemia. It can be hereditary (lack of lipoprotein lipase), acquired (obesity, chronic alcohol use), or a combination of both. Like hyperlipoproteinemia, hypertriglyceridemia increases the risk of vascular disease (atherosclerosis, coronary heart disease, peripheral vascular disease).


  • Fatty acid length
    • Short-chain fatty acid (SCFA): total carbon-chain length between 1–6
    • Medium-chain fatty acid (MCFA): total carbon-chain length between 7–12
    • Long-chain fatty acids (LCFA): total carbon-chain length between 13–20
    • Very long-chain fatty acid (VLCFA): total carbon-chain length 20
    • Odd-chain fatty acid: contains an odd number of carbon atoms
  • Fatty acid saturation
    • Saturated (without C=C double bonds)
    • Unsaturated fatty acids (with C=C double bonds)
      • Monounsaturated fatty acids: have one double bond
      • Polyunsaturated fatty acids: have > 1 double bonds
  • Nomenclature: Unsaturated fatty acids are named using the omega system.
    • The last carbon in the fatty acid molecule (i.e., the furthest from the carboxyl group) is labeled as ω (omega).
    • A fatty acid is given a name that reflects the position of the first double bond relative to omega-carbon

Excessive dietary intake of trans-unsaturated fatty acids (e.g., fried foods, margarine, and shortening) raises LDL levels and lowers HDL levels, thereby increasing the risk of cardiovascular events.

Essential fatty acids [4][5]

  • Definition: polyunsaturated fatty acids that cannot be synthesized by humans and need to be ingested
  • Types
    • Omega-3 fatty acids
      • Examples: alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)
      • Sources: nuts, seeds, cold-water fish, algae
      • Function
    • Omega-6 fatty acids
      • Examples: linoleic acid
      • Sources: cereals, soybeans, seeds, and seed oils
      • Function: Metabolized to arachidonic acid, which is a precursor for prostaglandins and leukotrienes
      • Clinical significance: Excessive intake, which often occurs in Western diets, promotes inflammation and is associated with an increased risk of cardiovascular events. [5]

Overview of fatty acid metabolism

The breakdown of fatty acids is not simply a reversal of fatty acid synthesis; there are a number of differences between the two processes.

Characteristics Synthesis Breakdown
Main goal
Rate-determining enzyme
  • Carnitine palmitoyltransferase I
Required substances
End products

The Sytrate (citrate) shuttle is essential for fatty acid Synthesis.

Fatty acids travel to their site of degradation by CARnitine.

Fatty acid synthesis



  1. Acetyl-CoA groups (from glycolysis) are transported from the mitochondria to the cytoplasm through the citrate shuttle.
  2. In the cytoplasm, ATP citrate lyase hydrolyzes citrate back into acetyl-CoA and oxaloacetate.
  3. Acetyl CoA carboxylase activates acetyl-CoA and converts it into malonyl-CoA.


Fatty acid synthesis is regulated via phosphorylation of acetyl-CoA carboxylase.

Fatty acid degradation [6]



  1. Fatty acid transport (into the mitochondria)
  2. Beta oxidation (in mitochondrial matrix): a catabolic process in which a fatty acid chain is cleaved (oxidized) at the beta carbon (every second carbon) by dehydrogenase enzymes in several cycles.


Clinical significance

Carnitine deficiency results in toxic accumulation of LCFA in the cytoplasm of myocytes and other cells. Patients present with hypoketotic hypoglycemia, fatty liver, myopathy, hypotonia, and fatigue. Treatment consists of oral supplementation of the amino acid carnitine.

MCAD deficiency is characterized by the defective breakdown of MCFA, which renders FAs an unusable alternative energy source in the case of carbohydrate deficiency. Because the liver cannot degrade FAs beyond C8–C10, acetyl-CoA and NADH are missing for ketone body production and gluconeogenesis. This deficiency results in nonketotic hypoglycemia, encephalopathy, and lethargy in fasting states. C8–C10 acylcarnitines can be found in the blood.

Degradation of very long-chain fatty acids (20 carbons)

Degradation of fatty acids with an odd number of carbon atoms (propionic acid pathway)

Triglyceride synthesis

Synthesized triglycerides are either stored in adipose tissue or transported to the muscle for energy utilization.

Triglyceride degradation

Ketone body metabolismtoggle arrow icon

Ketone bodies


Ketone body synthesis takes place exclusively in the mitochondria of hepatocytes. Ketone bodies are then released into the blood and transported to their target tissues (mainly the brain and muscle).

Two molecules of acetyl-CoA acetoacetyl-CoA HMG-CoA acetoacetate β-hydroxybutyrate. Acetone is formed by spontaneous decarboxylation of acetoacetate. The body has no use for acetone, which is excreted primarily via the lungs (gives breath a fruity odor). A small fraction is also exerted in the urine.


RBCs do not have mitochondria and hepatocytes lack the thiophorase enzyme. Therefore, neither of them can utilize ketone bodies for energy.

Cholesterol metabolismtoggle arrow icon


Excess cholesterol secretion into bile (e.g., in pregnancy, obesity) can lead to precipitation of cholesterol crystals and gallstone formation (cholelithiasis).

There is no intestinal absorption of cholesterol without bile salts. Bile salt deficiency can be caused by gallstones or a tumor of the biliary tract.

Cholesterol synthesis

Simplified cholesterol synthesis: acetyl-CoA acetoacetyl-CoA HMG-CoA mevalonate squalene → cholesterol

The enzyme HMG-CoA reductase is clinically important because it is the target for drugs that are designed to reduce the plasma concentration of cholesterol (i.e., HMG-CoA reductase inhibitors, which have a structure similar to that of mevalonate). They are also referred to as statins.

Clinical significancetoggle arrow icon

Laboratory considerations

  • In laboratory tests, total cholesterol, triglycerides, HDL, and LDL are usually measured.
  • If levels are elevated or reduced, testing should be repeated after at least 2 weeks.
  • See “Parameters of fat metabolism” for optimal and pathological levels.
Laboratory parameter Elevated in [7][8] Reduced in Prognostic correlations
Cholesterol HDL
  • Healthy lifestyle (physical activity)
  • Moderate alcohol consumption [9]
  • Healthy lifestyle (calorie restriction, physical activity)

Associated conditions


Referencestoggle arrow icon

  1. Nettleton JA, Lovegrove JA, Mensink RP, Schwab U. Dietary Fatty Acids: Is it Time to Change the Recommendations?. Annals of Nutrition and Metabolism. 2016; 68 (4): p.249-257.doi: 10.1159/000446865 . | Open in Read by QxMD
  2. Sokoła-Wysoczańska E, Wysoczański T, Wagner J, et al. Polyunsaturated Fatty Acids and Their Potential Therapeutic Role in Cardiovascular System Disorders—A Review. Nutrients. 2018; 10 (10): p.1561.doi: 10.3390/nu10101561 . | Open in Read by QxMD
  3. Schönfeld P, Wojtczak L. Short- and medium-chain fatty acids in energy metabolism: the cellular perspective. J Lipid Res. 2016; 57 (6): p.943-54.doi: 10.1194/jlr.R067629 . | Open in Read by QxMD
  4. Feingold KR et al. Introduction to Lipids and Lipoproteins. Endotext [Internet]. 2000.
  5. Kraemer FB, Shen W-J. Hormone-sensitive lipase. J Lipid Res. 2002; 43 (10): p.1585-1594.doi: 10.1194/jlr.r200009-jlr200 . | Open in Read by QxMD
  6. Persson E. Lipoprotein lipase, hepatic lipase and plasma lipolytic activity. Effects of heparin and a low molecular weight heparin fragment (Fragmin).. Acta Med Scand Suppl. 1988; 724: p.1-56.
  7. $The effect of endocrine disorders on lipids and lipoproteins.
  8. Attman P-O, Alaupovic P. Pathogenesis of hyperlipidemia in the nephrotic syndrome. Am J Nephrol. 1990; 10 (1): p.69-75.doi: 10.1159/000168197 . | Open in Read by QxMD
  9. De Oliveira e Silva ER, Foster D, McGee Harper M, et al. Alcohol Consumption Raises HDL Cholesterol Levels by Increasing the Transport Rate of Apolipoproteins A-I and A-II. Circulation. 2000; 102 (19): p.2347-2352.doi: 10.1161/01.cir.102.19.2347 . | Open in Read by QxMD
  10. Arnaldi G, Scandali VM, Trementino L, Cardinaletti M, Appolloni G, Boscaro M. Pathophysiology of dyslipidemia in Cushing’s syndrome. Neuroendocrinology. 2010; 92 (1): p.86-90.doi: 10.1159/000314213 . | Open in Read by QxMD

Icon of a lock3 free articles remaining

You have 3 free member-only articles left this month. Sign up and get unlimited access.
 Evidence-based content, created and peer-reviewed by physicians. Read the disclaimer