title: Does postprandial storage of triglycerides in endothelial cells contribute to the endothelial dysfunction associated with insulin resistance and fatty diets?
abstract: Insulin resistance syndrome is associated with endothelial dysfunction characterized by decreased nitric oxide bioactivity and subnormal endothelium-dependent vasodilation. Excessive exposure to free fatty acids (FFAs) is thought to mediate this dysfunction, at least in part, since free fatty acid overexposure, both in vivo and in vitro, decreases the capacity of endothelial cells to generate bioactive nitric oxide. Yet this endothelial dysfunction tends to correlate, not with fasting FFA levels, but with poor insulin suppressibility of FFA flux postprandially. I propose that triglycerides are synthesized and stored in endothelial cells during the postprandial period, when FFAs and insulin are jointly elevated, and that this triglyceride pool serves as a source of FFA overexposure postabsorptively--thus accounting for the endothelial dysfunction associated with insulin resistance syndrome and the role of excessive postprandial FFA flux in its induction. Since a substantial proportion of postprandial FFA flux derives, not from adipocytes, but from the fat provided by meals, these considerations may help to rationalize the documented clinical utility of very-low-fat diets for management of coronary disease.
authors.affiliation: Pantox Laboratories, San Diego, CA 92109, USA.
authors.forename: M F
authors.initials: MF
authors.lastname: McCarty
mesh_terms: D018752:Diet, Fat-Restricted / Q000009:adverse effects; D014676:Diet, Vegetarian; D004041:Dietary Fats / Q000009:adverse effects*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008954:Models, Biological; D019518:Postprandial Period / Q000502:physiology; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D014280:Triglycerides