High-energy diets, fatty acids and endothelial cell function: implications for atherosclerosis

J Am Coll Nutr. 2001 Apr;20(2 Suppl):97-105. doi: 10.1080/07315724.2001.10719021.


Diets high in fat and/or calories can lead to hypertriglyceridemia and postprandial lipemia and thus are considered a risk factor for the development of atherosclerosis. Plasma chylomicron levels are elevated in humans after consuming a high-fat meal, and hepatic synthesis of VLDL is increased when caloric intake is in excess of body needs. High lipoprotein lipase activity and subsequent hydrolysis of triglyceride-rich lipoproteins may be an important source of elevated concentrations of fatty acid anions in the proximity to the endothelium and hence a major risk factor for atherosclerosis. We have shown that selected fatty acids, as well as lipoprotein lipase-derived remnants of lipoproteins isolated from hypertriglyceridemic subjects, can activate vascular endothelial cells and disrupt endothelial integrity. Our studies suggest that omega-6 fatty acids, and especially linoleic acid, cause endothelial cell dysfunction most markedly as well as can potentiate TNF-mediated endothelial cell injury. We propose that high-energy diets, and especially diets rich in linoleic acid, are atherogenic by contributing to an imbalance in cellular oxidative stress/antioxidant status of the endothelium, which can lead to activation of oxidative stress-responsive transcription factors, inflammatory cytokine production and the expression of adhesion molecules. Our data also suggest that nutrients, which have antioxidant and/or membrane stabilizing properties, can protect endothelial cells. These findings contribute to the understanding of the interactive role of high fat/calorie diets and subsequent hypertriglyceridemia with inflammatory components and nutrients that exhibit antiatherogenic properties in the development of atherosclerosis. Moreover, results from our research further support the concept that high-fat/calorie diets and associated postprandial hypertriglyceridemia are significant risk factors for atherosclerosis.

Publication types

  • Review

MeSH terms

  • Antioxidants / pharmacology
  • Arteriosclerosis / blood
  • Arteriosclerosis / etiology*
  • Diabetes Mellitus, Type 2 / complications
  • Dietary Fats / administration & dosage*
  • Dietary Fats / metabolism
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology*
  • Energy Intake*
  • Fatty Acids, Omega-6
  • Fatty Acids, Unsaturated / adverse effects
  • Humans
  • Hyperlipidemias / complications*
  • Hyperlipidemias / metabolism
  • Hypertriglyceridemia / complications
  • Hypertriglyceridemia / metabolism
  • Oxidation-Reduction
  • Oxidative Stress
  • Postprandial Period
  • Risk Factors


  • Antioxidants
  • Dietary Fats
  • Fatty Acids, Omega-6
  • Fatty Acids, Unsaturated