Dietary oxidized fatty acids: an atherogenic risk?

Abstract

Previous studies have suggested that heated fat that contains oxidized fatty acids in the diet might contribute to the presence of oxidized components in circulating lipoproteins. On the other hand, studies in our laboratory showed that cultured cells such as smooth muscle cells take up oxidized fatty acids poorly. Because intestinal cells are morphologically quite distinct, we studied the uptake of oxidized linoleic acid by Caco-2 and smooth muscle cells (control). When 16-day-old Caco-2 cells were incubated with oxidized linoleic acid (ox-linoleic acid), its uptake was comparable to that of unoxidized linoleic acid (unox-linoleic acid) or that of oleic acid (40-58, 70, and 55%, respectively). In contrast, the uptake of ox-linoleate by smooth muscle cells was about 3%. To determine whether the brush border structure of Caco-2 cells was responsible for increased uptake of oxidized fatty acids, we compared uptake in 4-and 16-day-old cells. The uptake of unox-linoleate and oleic acid (18:1) was comparable for the 4-and 16-day cells. In addition, saturation and competition experiments showed that the uptake of ox-linoleate by Caco-2 cells is not saturable even at 150 M and that this uptake is diluted in the presence of unox-linoleate. In esterification experiments utilizing rat intestinal microsomes, we show that both ox-and unox-linoleate are esterified equally well. In summary, dietary oxidized fatty acids can be absorbed by the intestine and incorporated into lipoproteins and could potentially impose an oxidative stress and exacerbate atherogenesis. -

Dietary oxidized fatty acids may enhance intestinal apolipoprotein A-I production

“…After 20 h, culture medium from each dish was collected for apoA-I measurement, and the cell monolayer washed with PBS, solubilized in cell lysis buffer, and used for cellular protein measurement and Western blot analysis. Our previous study indicated that the presence or absence of albumin had no effect on the uptake of fatty acids (21). Furthermore, the intestinal lumen does not contain any albumin and fatty acids in the free form.…”

“…In vivo studies conducted in animals have clearly demonstrated that dietary oxidized lipids are absorbed by the intestine and released into the circulation within triacylglycerol-rich lipoproteins (17)(18)(19)(20). Our previous studies have shown that oxidized free fatty acids (ox-FFA) are efficiently taken up by Caco-2 cells, and the uptake was dependent on the presence of brush border structure (21). However, it is unknown whether ox-FFA will have any effect on intestinal apoA-I synthesis and secretion.…”

Enhanced solubilization and intestinal absorption of cholesterol by oxidized linoleic acid

“…The linoleic acid (3 mM) solution was oxidized with soybean lipoxidase (60 U/100 nmol, 2 h at 37 Њ C) to produce ox-18:2 [hydroperoxy octadecadienoic acid (HPODE) and hydroxy octadecadienoic acid (HODE)] (15,20). The formation of HPODE was determined by Leucomethylene blue (LMB) (21).…”

“…Studies in rodents by Kanazawa and others have shown that when animals are fed peroxidized fatty acids a certain percentage is found in the intestinal lumen and is incorporated into the liver and other organs (12)(13)(14). We recently reported the extent of absorption and subsequent metabolism of oxidized linoleic acid (ox-18:2) and unoxidized linoleic acid (unox-18:2) in Caco-2 cells and rat everted intestinal sacs (15). During the course of these experiments, we noted a similarity between ox-FFA and bile acids.…”

Commentary: Iconoclastic Reflections on the ‘Safety’ of Polyunsaturated Fatty Acid-Rich Culinary Frying Oils: Some Cautions regarding the Laboratory Analysis and Dietary Ingestion of Lipid Oxidation Product Toxins

“…In view of these considerations, such secondary LOPs give rise to a broad spectrum of concentration-dependent cellular stresses. The deleterious toxicological properties and health effects of these aldehydes represent one major consequential focus of this communication, and these include their adverse influence on critical metabolic pathways (for example, [26]); promotion and perpetuation of atherosclerosis and cardiovascular diseases [23,[27][28][29]); mutagenic and carcinogenic properties [30][31][32][33][34][35]; teratogenic actions (embryo malformations during pregnancy [36]; exertion of striking pro-inflammatory effects [10,37]; induction of gastropathic properties (peptic ulcers) following dietary ingestion [38]; neurotoxic actions, including those of 4-hydroxy-trans-2-nonenal (HNE) and -hexenal (HHE) [39]; and the adverse stimulation of significant increases in systolic blood pressure [40]. Further deleterious health effects include chromosomal aberrations, reflecting their clastogenic potential, and sister chromatid exchanges and point mutations, in addition to cell damage and death [41,42].…”