High-energy diets, fatty acids and endothelial cell function: implications for atherosclerosis.
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.
Hennig
B
B
Department of Animal Sciences, and Graduate Center for Nutritional Sciences, University of Kentucky, Lexington 40506-0054, USA. bhennig@pop.uky.edu
Toborek
M
M
McClain
C J
CJ
D000975:Antioxidants / Q000494:pharmacology; D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D004041:Dietary Fats / Q000008:administration & dosage* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002149:Energy Intake; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000009:adverse effects; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications* / Q000378:metabolism; D015228:Hypertriglyceridemia / Q000150:complications / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D019518:Postprandial Period; D012307:Risk Factors
D000975:Antioxidants; D004041:Dietary Fats; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated