Effects of docosahexaenoic acid on annular lipid fluidity of the rat bile canalicular plasma membrane (original) (raw)
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Journal of lipid research, 1993
The effect of docosahexaenoic acid (DHA) on mitochondrial and peroxisomal fatty acid oxidation and on key enzymes in triglyceride metabolism was investigated in the liver of rats fed a standard diet, a cholesterol diet, and a pelleted chow diet. Unexpectedly, in all three rat models repeated administration of highly purified DHA (92% pure) at different doses and times, at a dose of 1000 mg/day per kg body weight, resulted in no significant decrease of hepatic and plasma concentration of triglycerides. The serum concentrations of cholesterol and phospholipids showed an increase in a time-dependent manner in rats fed the pelleted chow diet. The hepatic concentration of cholesterol was increased in rats fed the cholesterol diet and pelleted chow diet after administration of DHA compared to palmitic acid. In all rat models, treatment with DHA tended to increase the peroxisomal beta-oxidation. This was accompanied with a significant increase (1.5-fold) of fatty acyl-CoA oxidase activity....
Lipids, 1997
Weanling male Wistar rats were fed for five weeks on standard rat chow (23 g fat/kg diet) or one of four synthetic diets with butterfat, coconut oil, corn oil, or fish oil as the main lipid source (100 g fat/kg diet). In all diets, 10% of the fat was provided as corn oil to prevent essential fatty acid deficiency. Significant differences were observed in the saturated, monounsaturated, and polyunsaturated fatty acid composition, and in the ratio of cholesterol to phospholipid, in the hepatocyte membranes. The fluidity of hepatocyte plasma membranes was assessed using the fluorescence recovery after photobleaching technique and steady-state fluorescence anisotropy of diphenylhexatriene. No significant differences were found in the fluidity of plasma membranes between animals on the different fat diets, despite diet-induced changes in their fatty acid composition. However, the proportion of lipid free to diffuse in the plasma membrane varied with diet, being significantly greater (P < 0.05) in animals fed chow (63.7%), coconut oil (61.5%), and butterfat (57.6%) diets than in those fed the corn oil (47.3%) diet. Animals fed fish oil showed an intermediate (50.0%) proportion of lipid free to diffuse. The data support the hypothesis that dietary lipids can change both the chemical composition and lateral organization (lipid domain structure) of rat hepatocyte plasma membranes.
The Journal of Lipid Research
The amount and distribution of [ 13 C]docosahexaenoic acid (DHA) in plasma, platelet, and erythrocyte lipid classes were followed as a function of time (1 to 72 h) in young adults after ingestion of a single dose of [ 13 C]DHA esterified in a phosphatidylcholine (PC), in using gas chromatography combustion-isotope ratio mass spectrometry. [ 13 C]DHA first appeared in plasma non-esterified fatty acids (NEFA) and triglycerides (TG), with a maximal appearance at 6 h and a further decline, then being delayed 3-fold compared to [ 13 C]DHA ingested in triglycerides. Lysophosphatidylcholine (LPC) was also enriched in [ 13 C]DHA, due mainly to earlier hepatic secretion, and plateaued at 6 h, whereas phosphatidylethanolamine (PE) and phosphatidylcholine (PC) containing [ 13 C]DHA plateaued at 9 h. The labeling of erythrocyte and platelet phospholipids exhibited different kinetics, probably involving different metabolic pathways for [ 13 C]DHA incorporation in cell membranes. Computation of the relative contribution of LPC and NEFA for delivery of [ 13 C]DHA to blood cells showed that the supply to platelets occurred through NEFA. In contrast, [ 13 C]DHA was carried by both LPC and NEFA to erythrocytes, which differs from what was previously been observed after intake of triglycerides labeled with [ 13 C]DHA where LPC was the only source of [ 13 C]DHA for erythrocytes. We conclude that the lipid form of ingested DHA affects markedly its kinetics and partly its metabolic fate.-Lemaitre-Delaunay, D., C. Pachiaudi, M. Laville, J. Pousin, M. Armstrong, and M. Lagarde. Blood compartmental metabolism of docosahexaenoic acid (DHA) in humans after ingestion of a single dose of [ 13 C]DHA in phosphatidylcholine.
Journal of Clinical Investigation, 1991
Hepatic cholesterol metabolism was studied in rats fed purified diets supplemented (9% wt/wt) with either fish oil (FO) (n-3 fatty acids) or corn oil (CO) (n-6 fatty acids) for 4 wk. Rats were equipped with permanent catheters in heart, bile duct, and duodenum to allow studies under normal feeding conditions. [3H, cholesteryl oleate-labeled small unilamellar liposomes, which are rapidly endocytosed by hepatocytes, were intravenously injected to label intrahepatic cholesterol pools, and plasma and bile were collected. FO as compared to CO induced a lowering of plasma cholesterol levels by 38% and oftriglyceride levels by 69%. This reduction in plasma lipids in FO rats was accompanied by: (a) an increased bile acid pool size (28%); (b) a fourfold increase in the ratio cholic acid/chenodeoxycholic acid in bile; (c) increased biliary excretion of cholesterol (51%) (d) accelerated excretion of endocytosed free cholesterol into bile; (e) accelerated incorporation ofendocytosed cholesterol in bile acids; (f) a significant increase in the bile acid-independent fraction of bile flow, and (g) a threefold increase in hepatic alkaline phosphatase activity. The results show that FO induces changes in transport and metabolic pathways of cholesterol in the rat liver, which result in a more rapid disposition of plasmaderived cholesterol into the bile.
Journal of Nutritional Biochemistry, 2011
To investigate the effect of docosahexaenoic acid (DHA) without other highly unsaturated fatty acids (HUFA) on n-3 and n-6 essential fatty acid (EFA) metabolism and fatty acid composition in mammals, a stable isotope tracer technique was used in adult rats fed diets with or without 1.3% of algal DHA in a base diet containing 15% of linoleic acid and 3% of alpha-linolenic acid over 8 weeks. The rats were administered orally a mixed oil containing 48 mg/kg body weight of deuterated linoleic and alpha-linolenic acids and euthanized at 4, 8, 24, 96, 168, 240, 360 and 600 h after administration of the isotopes. Fatty acid compositions and the concentrations of deuterated precursors and their respective metabolites were determined in rat liver, plasma, heart and brain as a function of time. DHA, docosapentaenoic acid and eicosapentaenoic acid in the n-3 EFA family were significantly increased in all organs tested in the DHA-fed group, ranging from 5 to 200% greater in comparison with the control group. The accumulation of the metabolites, deuterated-DHA and deuterated-docosapentaenoic acid n-6 were greatly decreased by 1.5 to 2.5 fold in the dietary DHA group. In summary, feeding preformed DHA led to a marked increase in n-3 HUFA content of rat organs at the expense of n-6 HUFA and also prevented the accumulation of newly synthesized deuterated end products. This is the first study which has isolated the effects of DHA on the de novo metabolism on both the n-6 and n-3 EFA pathways.
Molecular and cellular biochemistry, 2006
Animal studies suggest that the 2 major 3 fatty acids found in fish, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may have differential effects on blood pressure (BP) and heart rate (HR). The aim of this study was to determine whether there were significant differences in the effects of purified EPA or DHA on ambulatory BP and HR in humans. In a double-blind, placebo-controlled trial of parallel design, 59 overweight, mildly hyperlipidemic men were randomized to 4 g/d of purified EPA, DHA, or olive oil (placebo) capsules and continued their usual diets for 6 weeks. Fifty-six subjects completed the study. Only DHA reduced 24-hour and daytime (awake) ambulatory BP (PϽ0.05). Relative to the placebo group, 24-hour BP fell 5.8/3.3 (systolic/diastolic) mm Hg and daytime BP fell 3.5/2.0 mm Hg with DHA. DHA also significantly reduced 24-hour, daytime, and nighttime (asleep) ambulatory HRs (Pϭ0.001). Relative to the placebo group, DHA reduced 24-hour HR by 3.5Ϯ0.8 bpm, daytime HR by 3.7Ϯ1.2 bpm, and nighttime HR by 2.8Ϯ1.2. EPA had no significant effect on ambulatory BP or HR. Supplementation with EPA increased plasma phospholipid EPA from 1.66Ϯ0.07% to 9.83Ϯ0.06% (PϽ0.0001) but did not change DHA levels. Purified DHA capsules increased plasma phospholipid DHA levels from 4.00Ϯ0.27% to 10.93Ϯ0.62% (PϽ0.0001) and led to a small, nonsignificant increase in EPA (1.52Ϯ0.12% to 2.26Ϯ0.16%). Purified DHA but not EPA reduced ambulatory BP and HR in mildly hyperlipidemic men. The results of this study suggest that DHA is the principal 3 fatty acid in fish and fish oils that is responsible for their BP-and HR-lowering effects in humans. These results have important implications for human nutrition and the food industry. (Hypertension. 1999;34:253-260.) Key Words: eicosapentaenoic acid Ⅲ docosahexaenoic acid Ⅲ fatty acids Ⅲ blood pressure Ⅲ heart rate C urrent evidence from epidemiological studies, clinical
NeuroMolecular Medicine, 2020
The abundance of docosahexaenoic acid (DHA) in phospholipids in the brain and retina has generated interest to search for its role in mediating neurological functions. Besides the source of many oxylipins with pro-resolving properties, DHA also undergoes peroxidation, producing 4-hydroxyhexenal (4-HHE), although its function remains elusive. Despite wide dietary consumption, whether supplementation of DHA may alter the peroxidation products and their relationship to phospholipid species in brain and other body organs have not been explored sufficiently. In this study, adult mice were administered a control or DHA-enriched diet for three weeks, and phospholipid species and peroxidation products were examined in brain, heart and plasma. Results demonstrated that this dietary regimen increased (n-3) and decreased (n-6) species to different extent in all major phospholipid classes (PC, dPE, PE-pl, PI and PS) examined. Besides changes in phospholipid species, DHA-enriched diet also showed substantial increases in 4-HHE in brain, heart and plasma. Among different brain regions, the hippocampus responded to the DHA-enriched diet showing significant increase in 4-HHE. Considering the pro-and anti-inflammatory pathways mediated by the (n-6) and (n-3) polyunsaturated fatty acids, unveiling the ability for DHA-enriched diet to alter phospholipid species and lipid peroxidation products in the brain and in different body organs may be an important step forward towards understanding the mechanism(s) for this (n-3) fatty acid on health and diseases.
Journal of Functional Foods, 2019
In this study, under dyslipidemia (D) and dyslipidemia with diabetes (DD) conditions, we assessed the intestinal bile acid (BA) uptake, BA transporter expression and de novo BA synthesis in rats. The restorative potentials n-3 fatty acids [{α-linolenic acid (ALA), DD + canola oil (CNO)} and eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA), DD + fish oil (FO)}] were also assessed. DD group had significantly (p < 0.05) increased intestinal BA uptake and Asbt and Osta/b mRNA expression, increased serum BA level, decreased hepatic Ntcp, Bsep and Cyp7a1 mRNA expression, increased hepatic HMG-CoA reductase activity, increased hepatic Fxr and Shp mRNA expression, decreased hepatic Lrh-1 and Hnf4a mRNA expression and decreased fecal BA level, when compared to control, D, DD + CNO, and DD + FO group. Our data show for the first time that, hyperglycemia exacerbates dyslipidemia-induced dysregulation of BA metabolism and transport. Dietary EPA + DHA exhibited superior effect than ALA in normalizing dyslipidemia and hyperglycemia-induced disturbances.