Triglycerides

Triacylglycerols—commonly known as triglycerides—are a type of lipid that contains a glycerol backbone to which three fatty acid molecules of various lengths are bound. As such, triglycerides are molecules very rich in energy. That is why all organisms use some form of triglyceride to store fatty acids in adipose tissue for energy and heat production, cell membrane synthesis, and organ protection. 

We take up triglycerides when we ingest food (for example, with butter and oil), but the liver can also synthesize triglycerides from extra calories. The human body stores triglycerides in lipid droplets within fat cells and fat tissue throughout the body. When the body later needs energy, it will degrade the triglycerides and “burn fat.” Even though triglycerides are necessary for the body’s energy metabolism, increased amounts of fatty tissue are unhealthy for the body. People with high triglyceride levels are at an increased risk for heart disease, heart attack, stroke, and metabolic syndrome. A healthy diet, physical activity, and regular exercise can reduce extra fat tissue and the risk of cardiovascular diseases.

Origin, Transport, and Storage of Triglycerides

When eating food, bile acids in the intestine emulsify the fatty molecules (such as cholesterol) and free fatty acids, as well as animal- and plant-derived triglycerides. The cells in the intestinal system take up these emulsified molecules and hydrolyze the triglycerides into free fatty acids. All fatty molecules are then packed into chylomicrons that are secreted into the bloodstream, distributed into the body, or transported to the liver. Liver cells attach three fatty acid molecules to one glycerol-3-phosphate molecule, thus producing triglycerides. These are then stored in lipid droplets within the liver or attached to lipoproteins together with cholesterol and secreted as very-low-density lipoproteins (VLDL) into the bloodstream.

Chylomicrons and VLDLs transport triglycerides and cholesterol to various tissues and organs. Throughout this process, the lipoproteins encounter different cell receptors that cleave off the fatty acids from the triglycerides. The cell then takes up the free fatty acids to use them for energy production or membrane synthesis. This leaves cholesterol-enriched smaller low-density lipoproteins (LDLs, i.e., bad cholesterol), which are transported back to the liver.¹

Excess fatty acids and triglycerides are mainly stored in lipid droplets in the white adipose tissue and in smaller amounts in the liver. Additionally, unused calories from sugar and alcohol can be converted into fatty acids and stored as triglycerides. During periods of fasting or starvation, hormones, such as thyroid hormones, release the triglycerides from the fat tissue to provide the body and muscles with fatty acids and energy.²

Triglycerides and Metabolic Health

Storing energy in the form of triglycerides is essential for the body’s metabolism and protection of organs. Since fatty acids are essential components of cell membranes, the body requires sufficient amounts to grow and develop. However, high concentrations of lipid droplets and fat cells can be problematic for tissues and organs that are not made for excessive fat storage, such as the liver. Increased triglyceride load in the liver can lead to an altered lipid metabolism, lipid disorders, and even non-alcoholic fatty liver disease.

High blood triglyceride levels with increased secretion of VLDL into the blood can result in pancreatitis, obesity, insulin resistance, and diabetes, also known together as metabolic syndrome.³ As LDLs distribute triglycerides and fatty acids in the body, cleaving them off can lead to local high levels of fatty acids. These can trigger inflammation and promote the onset of diabetes. Furthermore, increased levels of lipoproteins enriched in triglycerides in the blood reduce the levels of high-density lipoproteins. This is the so-called “good” cholesterol, as it collects excess cholesterol and transports it back to the liver for clearance.⁴ Hence, the aim should be to keep blood triglyceride levels low to prevent inflammation, metabolic syndrome, and weight gain.

Triglycerides and Heart Disease

Recent research studies also show that high triglyceride levels profoundly impact the health of the heart. Similar to other cells, heart muscle cells cleave off fatty acids from triglyceride-rich VLDLs from the blood and take up the free fatty acids. The majority of these fatty acids is used for energy production and, thus, for the functioning of the heart muscle or for membrane synthesis. Yet, a small amount is re-synthesized into triglycerides to store in lipid droplets. However, the heart is a non-fat tissue. Hence, the accumulation of triglycerides and lipid droplets can result in lipotoxicity, high blood pressure, and cardiac dysfunction.⁵

A further line of research suggests that, like high cholesterol, high blood triglycerides are risk factors for atherosclerosis.⁶ While the proportion of cholesterol in the LDL form is a crucial contributor to the formation of atherosclerotic plaques, the causal mechanism of triglycerides is suggested but not clearly understood yet.

One theory implies that large triglyceride-rich lipoprotein remnants tend to get trapped in the arterial wall and may cause the build-up of atherosclerotic plaques.⁷ Other studies suggest that macrophages in the arterial wall take up smaller lipoproteins rich in triglycerides and cholesterol. While macrophages can catabolize triglycerides, the cholesterol accumulates so that the macrophages become deformed and dysfunctional. These are then the onset of atherosclerotic plaques.⁸

Healthy Triglyceride Levels and Lifestyle Habits

Triglycerides are essential for the human body, its metabolism, growth, and basic functioning. Yet, high triglyceride levels can lead to serious health problems. Monitoring cardiovascular risk factors and triglyceride levels via routine LDL, HDL, and total cholesterol tests and lipid panels are an important disease management and prevention strategy, helping to prevent high triglycerides, manage high blood pressure and high blood sugar, and lower the risk of heart diseases.

Like the closely related cholesterol, triglycerides may be managed through lifestyle changes. Studies have shown that diets with reduced carbohydrate and saturated fat intake and increased Omega-3 fatty acids (from fish and fish oil) can lower triglycerides and decrease inflammation.⁹ Similarly, physical activity and avoidance of alcohol have been shown to lower triglycerides and the risk of heart disease, heart attack, and lipid disorders.^8,9

Triglycerides in Research

As of August 2023, there are nearly 29,000 citations for “triglycerides” in research publications (*excluding books and documents) on PubMed. The extensive number of publications linking triglyceride levels with cardiovascular health and disease emphasizes the benefit of triglyceride quantification to help better understand the role of these molecules in heart health and disease. Many publications also center around clinical management and understanding of triglycerides; therefore, preclinical research may also benefit from triglyceride quantification. Metabolon’s Complex Lipids Targeted Panel includes accurate quantification of over 500 species of triglycerides. Learn more about Metabolon’s quantitative lipidomic analysis here. 

References

1. Basu D, Goldberg IJ. Regulation of lipoprotein lipase-mediated lipolysis of triglycerides. Curr Opin Lipidol 2020;31(3):154-160.
2. Alves-Bezerra M, Cohen DE. Triglyceride Metabolism in the Liver. Compr Physiol 2017;8(1):1-8.
3. Hu X, Liu Q, Guo X, et al. The role of remnant cholesterol beyond low-density lipoprotein cholesterol in diabetes mellitus. Cardiovasc Diabetol 2022;21(1):117.
4. Castañer O, Pintó X, Subirana I, et al. Remnant Cholesterol, Not LDL Cholesterol, Is Associated With Incident Cardiovascular Disease. J Am Coll Cardiol 2020;76(23):2712-2724.
5. Yamamoto T, Sano M. Deranged Myocardial Fatty Acid Metabolism in Heart Failure. Int J Mol Sci 2022;23(2):996.
6. Farnier M, Zeller M, Masson D, et al. Triglycerides and risk of atherosclerotic cardiovascular disease: An update. Arch Cardiovasc Dis 2021;114(2):132-139.
7. Balling M, Afzal S, Varbo A, et al. VLDL Cholesterol Accounts for One-Half of the Risk of Myocardial Infarction Associated With apoB-Containing Lipoproteins. J Am Coll Cardiol 2020;76(23):2725-2735.
8. Laufs U, Parhofer KG, Ginsberg HN, Hegele RA. Clinical review on triglycerides. Eur Heart J 2020;41(1):99-109c.
9. Sandesara PB, Virani SS, Fazio S, et al. The Forgotten Lipids: Triglycerides, Remnant Cholesterol, and Atherosclerotic Cardiovascular Disease Risk. Endocr Rev 2019;40(2):537-557.