What are triglycerides?

What Are Triglycerides?

Triglycerides are hydrophobic lipid molecules that form the core of lipoproteins in plasma and serve as the body's primary form of stored energy. 1

Structure and Composition

• Triglycerides are macromolecular complexes that, along with cholesteryl esters, compose the core of lipoproteins in plasma 1
• They are hydrophobic in nature, requiring specialized transport mechanisms in the bloodstream 1
• Hundreds to thousands of triglyceride molecules can be carried in the core of different lipoproteins 1
• The core of lipoproteins containing triglycerides is covered by a unilamellar surface that contains amphipathic (both hydrophobic and hydrophilic) phospholipids, free cholesterol, and proteins called apolipoproteins 1

Metabolism and Transport

• After a meal, dietary fat and cholesterol are absorbed into cells of the small intestine and incorporated into nascent chylomicrons 1
• Newly formed chylomicrons contain 80-95% triglycerides and are secreted into the lymphatic system before entering circulation 1
• In the bloodstream, chylomicrons acquire apolipoproteins (apo CII, apo CIII, and apo E) 1
• In capillary beds of adipose tissue and muscle, triglycerides are hydrolyzed by lipoprotein lipase (LPL) after activation by apo CII 1
• The resulting free fatty acids can be taken up by fat cells and reincorporated into triglycerides for storage or used by muscle cells for energy 1

Types of Triglyceride-Rich Lipoproteins

• Chylomicrons: Intestinally-derived particles that transport dietary triglycerides 1
• Very Low-Density Lipoproteins (VLDL): Hepatic-derived particles that transport endogenously synthesized triglycerides 1
• Remnant Lipoprotein Particles (RLPs): Products of triglyceride hydrolysis in chylomicrons and VLDL 1

Clinical Significance

• The American Heart Association defines optimal fasting triglyceride levels as <100 mg/dL 1
• Elevated triglyceride levels serve as an important biomarker of cardiovascular disease (CVD) risk 1
• Triglycerides themselves are not directly atherogenic but represent risk through their association with atherogenic remnant particles and apo CIII 1
• Very high triglyceride levels (>500 mg/dL) increase risk for pancreatitis 1
• Hypertriglyceridemia is classified as:
  • Borderline high: 150-199 mg/dL
  • High: 200-499 mg/dL
  • Very high: ≥500 mg/dL 1

Causes of Elevated Triglycerides

• Primary genetic disorders: Familial combined hyperlipidemia (FCHL), familial hypertriglyceridemia (FHTG), and familial type III hyperlipoproteinemia 1
• Secondary causes: Obesity, insulin resistance, diabetes mellitus, metabolic syndrome, excessive alcohol consumption, and certain medications 1
• Body mass index (BMI) is strongly associated with hypertriglyceridemia, with higher BMI correlating with higher triglyceride levels 1

Treatment Considerations

• Treatment of elevated triglycerides focuses primarily on intensive therapeutic lifestyle changes 1
• A 5-10% reduction in body weight can reduce triglyceride levels by approximately 20% 1
• Reduction in carbohydrate calories, especially added sugars and fructose, while increasing unsaturated fat intake may contribute an additional 10-20% reduction in triglyceride levels 1
• For very high triglyceride levels (>500 mg/dL), medications such as fibrates (gemfibrozil, fenofibrate) may be indicated to reduce pancreatitis risk 2, 3

Clinical Pitfalls

• As triglyceride levels increase, the proportion of triglyceride to cholesteryl esters in VLDL increases, which results in underestimation of LDL-C based on the Friedewald formula 1
• Nonfasting triglyceride levels should not be used in the definition of metabolic syndrome or in the calculation of LDL-C 1
• In patients with hypertriglyceridemia, non-HDL-C or apolipoprotein B measurements may better reflect cardiovascular risk than LDL-C alone 1