“Ex Vivo” Influence of Fatty Acids from Plasma Cholesterol and Triglycerides on the Fatty Acid Pattern of Platelets

1985 ◽  
Vol 54 (03) ◽  
pp. 669-674 ◽  
Author(s):  
Justo Aznar ◽  
Teresa Santos ◽  
Juana Vallés
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Plasma Lipids ◽  
Ex Vivo ◽  
Plasma Cholesterol ◽  
Fatty Acid Pattern ◽  
Plasma Lipid ◽  
Normal Subjects ◽  
Lipid Fractions

SummaryWe have studied “ex vivo”, in 92 normal subjects, the influence of fatty acids (FA) that esterify plasma cholesterol and triglycerides on the fatty acid composition of phospholipids, triglycerides and free fatty acid fractions in platelets.High and significant correlations (p <0.001) were found for some of the platelet phospholipid FA and the same FA that esterify plasma cholesterol [18:11 (r = 0.56); 18:2 (r = 0.71) and 20:5 (r = 0.42)] and plasma triglycerides [18:1* (r = 0.57) and 18:2 (r = 0.66)]. Some significant correlations were also found between some of the platelet triglyceride FA and the same FA that esterify plasma phospholipids [18:1 (r = 0.58)], triglycerides [18:1 (r = 0.51), 18:2 (r = 0.52)] cholesterol [18:1 (r = 0.44)] and plasma free fatty acids [18:1 (r = 0.39); 18:2 (r = 0.40)].By evaluating these results in conjunction with those of an earlier study (1), it can be concluded that “ in vivo” the FA from different plasma lipid fractions and especially those esterifying the plasma cholesterol and phospholipid fractions, can influence the FA composition of platelet phospholipids in normal subjects. In trying to interpret the role played by plasma lipids in platelet lipids, it may be of interest to take into account the interrelationships found in this study.

Influence of Some Plasma Fatty Acids on the Phospholipid Fatty Acid Pattern of Human Platelets – An “Ex Vivo” Experience

1984 ◽  
Vol 52 (03) ◽  
pp. 232-235 ◽  
Author(s):  
Juana Vallés ◽  
Justo Aznar ◽  
M Teresa Santos
Keyword(s):  
Fatty Acids ◽  
Ex Vivo ◽  
Phospholipid Fatty Acid ◽  
Fatty Acid Pattern ◽  
Plasma Phospholipid ◽  
Normal Subjects ◽  
Human Platelets ◽  
Plasma Lipoproteins ◽  
Fa Composition

SummarySome correlations between plasma and platelet fatty acids (FA) were evaluated “ex vivo” in 94 normal subjects.The highest relationships between total FA from plasma and platelets were found for 18:1 (r = 0.74) and 18:2 (r = 0.67). Low correlations were obtained for free fatty acids (FFA). The most significant correlations between fatty acids esterifying plasma and platelet phospholipids were found for the 18:1 (r = 0.66); 18:2 (r = 0.74) and 20:5 (r = 0.66).Our results suggest that the platelet phospholipid FA could be more easily modified by plasma variation in the FA composition of phospholipids than by variations in the plasma FA composition of the FFA fraction. In addition, the incorporation of FA from plasma into the platelet phospholipids “in vivo” may take place through an acylation-deacylation process and also by the incorporation of whole plasma phospholipid molecules into the platelets, probably through an exchange of plasma lipoproteins and platelets. Finally, arachidonic acid seems to have a different and selective way of incorporation into platelet phospholipids.

Profiling substrate fluxes in the isolated working mouse heart using 13C-labeled substrates: focusing on the origin and fate of pyruvate and citrate carbons

2004 ◽  
Vol 286 (4) ◽  
pp. H1461-H1470 ◽  
Author(s):  
Maya Khairallah ◽  
François Labarthe ◽  
Bertrand Bouchard ◽  
Gawiyou Danialou ◽  
Basil J. Petrof ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Ex Vivo ◽  
Heart Function ◽  
Acid Oxidation ◽  
Mouse Heart ◽  
Relative Contribution ◽  
Cardiac Functions ◽  
Lactate And Pyruvate

The availability of genetically modified mice requires the development of methods to assess heart function and metabolism in the intact beating organ. With the use of radioactive substrates and ex vivo perfusion of the mouse heart in the working mode, previous studies have documented glucose and fatty acid oxidation pathways. This study was aimed at characterizing the metabolism of other potentially important exogenous carbohydrate sources, namely, lactate and pyruvate. This was achieved by using 13C-labeling methods. The mouse heart perfusion setup and buffer composition were optimized to reproduce conditions close to the in vivo milieu in terms of workload, cardiac functions, and substrate-hormone supply to the heart (11 mM glucose, 0.8 nM insulin, 50 μM carnitine, 1.5 mM lactate, 0.2 mM pyruvate, 5 nM epinephrine, 0.7 mM oleate, and 3% albumin). The use of three differentially 13C-labeled carbohydrates and a 13C-labeled long-chain fatty acid allowed the quantitative assessment of the metabolic origin and fate of tissue pyruvate as well as the relative contribution of substrates feeding acetyl-CoA (pyruvate and fatty acids) and oxaloacetate (pyruvate) for mitochondrial citrate synthesis. Beyond concurring with the notion that the mouse heart preferentially uses fatty acids for energy production (63.5 ± 3.9%) and regulates its fuel selection according to the Randle cycle, our study reports for the first time in the mouse heart the following findings. First, exogenous lactate is the major carbohydrate contributing to pyruvate formation (42.0 ± 2.3%). Second, lactate and pyruvate are constantly being taken up and released by the heart, supporting the concept of compartmentation of lactate and glucose metabolism. Finally, mitochondrial anaplerotic pyruvate carboxylation and citrate efflux represent 4.9 ± 1.8 and 0.8 ± 0.1%, respectively, of the citric acid cycle flux and are modulated by substrate supply. The described 13C-labeling strategy combined with an experimental setup that enables continuous monitoring of physiological parameters offers a unique model to clarify the link between metabolic alterations, cardiac dysfunction, and disease development.

An ω-6 Fatty Acid, Dgla, Prevents Platelet Activation and Thrombosis in Vivo.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2169-2169
Author(s):  
Jennifer Yeung ◽  
Kenneth Ikei ◽  
Joanne Vesci ◽  
Theodore R Holman ◽  
Michael Holinstat
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Conflicts Of Interest ◽  
Ex Vivo ◽  
Dietary Supplementation ◽  
Bioactive Metabolites ◽  
Induce Platelet Aggregation

Abstract Abstract 2169 Platelets play a pivotal role in thrombotic events leading to clot formation and clot stability in vivo. Uncontrolled signaling events in the platelet can result in unwanted thrombosis, which may eventually lead to the development of myocardial infarction or stroke. Previously, we have shown that ex vivo treatment of human platelets with the ω-6 fatty acid dihomo-γ-linolenic acid (DGLA) or its eicosanoid derived from 12-LOX oxidation, 12-hydroxyeicosatrienoic acid (12(S)-HETrE), inhibits PAR and collagen-induced platelet aggregation, clot retraction, and GPIIbIIIa activation. Since early studies have shown dietary supplementation of fatty acids increase fatty acid incorporation into the platelet lipid membrane (Barre, DE Lipids 1992; 27(5): 315–320; Marry, MJ Prostaglandins Leukot Essent Fatty Acids 1997; 56(3):223–223), we postulated that altering fatty acid composition in the platelet through dietary supplementation in vivo may be a viable approach to inhibiting platelet function. Therefore, a longitudinal study of wild-type mice on normal chow compared to mice supplemented with high (.5 g/kg) or low (.13 g/kg) DGLA diets was conducted. Each set of mice (7–8 mice) was given the designated diet for a period of 1, 2, or 3 months. At each time point, tail bleeding times and ex vivo platelet function in PRP were performed. Tail bleeding times from mice on the high DGLA diet were significantly prolonged by more than 15 minutes. Further, a smaller but statistically significant delay in clotting time was observed in mice on the low DGLA diet compared with control mice. Additionally, ex vivo aggregation response to collagen (1 μg/mL to 20 μg/mL) and PAR4-AP (50 μM to 500 μM) in platelets from mice on the high DGLA diet showed significant shifts to the right in their ability to induce platelet aggregation compared with control mice suggesting these mice were protected against thrombosis. JON/A and P-selectin binding to the PRP of high and low DGLA were also significantly attenuated in response to PAR4-AP. This study, which evaluated the in vivo and ex vivo effects of DGLA on regulation of platelet reactivity, supports DGLA as a potent, endogenous anti-thrombotic agent. Understanding the mechanistic details by which DGLA protects against thrombosis and maintains hemostasis through its COX-1 and 12-LOX-dependent bioactive metabolites will help to identify the potential viability of this target for anti-platelet intervention. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Incorporation and washout of orally administered n-3 fatty acid ethyl esters in different plasma lipid fractions

1999 ◽  
Vol 82 (6) ◽  
pp. 481-488 ◽  
Author(s):  
Sonja D. Zuijdgeest-van Leeuwen ◽  
Pieter C. Dagnelie ◽  
Trinet Rietveld ◽  
J.Willem O. van den Berg ◽  
J. H. Paul Wilson
Keyword(s):  
Fatty Acid ◽  
Half Life ◽  
Plasma Lipids ◽  
Plasma Lipid ◽  
Fatty Acid Ethyl Esters ◽  
Ethyl Esters ◽  
Second Phase ◽  
Dosing Schedule ◽  
Epa And Dha ◽  
Lipid Fractions

The aim of the present study was to quantify the incorporation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) into plasma lipids after oral administration of n-3 fatty acid ethyl esters, since little is known about the rate and pattern of incorporation into plasma lipid fractions. In addition, we aimed to obtain preliminary information regarding EPA half-life, which is needed to establish an optimal dosing schedule. Five healthy volunteers ingested two 8·5 g doses of n-3 fatty acid ethyl esters daily for 7 d, supplying 6·0 g EPA/d and 5·3 g DHA/d. The fatty acid compositions of plasma phospholipids (PL), cholesteryl esters (CE) and triacylglycerols (TAG) were determined during supplementation and during a washout period of 7 d. Half-lives of EPA and DHA were calculated. The proportion of EPA in PL showed a 15-fold increase after 7 d (P < 0·001), while DHA showed a smaller increase (P < 0·01). In CE, EPA also increased (P < 0·05), while DHA did not increase at all. Remarkably, incorporation of DHA into TAG was even higher than that of EPA. Half-life of EPA in PL ranged from 1·63 to 2·31 d (mean 1·97 (se 0·15) d), whereas mean half-life of EPA in CE was 3·27 (se 0·56) d. In three subjects, washout of EPA and DHA from TAG seemed to follow a bi-exponential pattern, with a short half-life (< 1 d) in the initial phase and a half-life of several days in the second phase. In conclusion, EPA ethyl esters are rapidly incorporated into plasma lipids, especially into PL. The relatively long half-life of EPA in plasma would permit a dosing schedule with intervals of ≥12 h in supplementation studies.

scholarly journals Cocktail biosynthesis of triacylglycerol by rational modulation of diacylglycerol acyltransferases in industrial oleaginous Aurantiochytrium

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Chuanzeng Lan ◽  
Sen Wang ◽  
Huidan Zhang ◽  
Zhuojun Wang ◽  
Weijian Wan ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Ex Vivo ◽  
Saturated Fatty Acids ◽  
Degree Of Unsaturation ◽  
Promising Target ◽  
Oleaginous Microorganism ◽  
Key Enzyme ◽  
Functional Distribution

Abstract Background Triacylglycerol (TAG) is an important storage lipid in organisms, depending on the degree of unsaturation of fatty acid molecules attached to glycerol; it is usually used as the feedstock for nutrition or biodiesel. However, the mechanism of assembly of saturated fatty acids (SFAs) or polyunsaturated fatty acids (PUFAs) into TAGs remains unclear for industrial oleaginous microorganism. Results Diacylglycerol acyltransferase (DGAT) is a key enzyme for TAG synthesis. Hence, ex vivo (in yeast), and in vivo functions of four DGAT2s (DGAT2A, DGAT2B, DGAT2C, and DGAT2D) in industrial oleaginous thraustochytrid Aurantiochytrium sp. SD116 were analyzed. Results revealed that DGAT2C was mainly responsible for connecting PUFA to the sn-3 position of TAG molecules. However, DGAT2A and DGAT2D target SFA and/or MUFA. Conclusions There are two specific TAG assembly routes in Aurantiochytrium. The “saturated fatty acid (SFA) TAG lane” primarily produces SFA-TAGs mainly mediated by DGAT2D whose function is complemented by DGAT2A. And, the “polyunsaturated fatty acid (PUFA) TAG lane” primarily produces PUFA-TAGs via DGAT2C. In this study, we demonstrated the functional distribution pattern of four DGAT2s in oleaginous thraustochytrid Aurantiochytrium, and provided a promising target to rationally design TAG molecular with the desired characteristics.

scholarly journals Effects of sirolimus on plasma lipids, lipoprotein levels, and fatty acid metabolism in renal transplant patients

2002 ◽  
Vol 43 (8) ◽  
pp. 1170-1180 ◽  
Author(s):  
Joel D. Morrisett ◽  
Ghada Abdel-Fattah ◽  
Ron Hoogeveen ◽  
Eddie Mitchell ◽  
Christie M. Ballantyne ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Renal Transplant ◽  
Lipase Activity ◽  
Plasma Lipids ◽  
Plasma Cholesterol ◽  
Transplant Rejection ◽  
Plasma Lipid ◽  
Immunosuppressive Drug ◽  
Transplant Patients ◽  
Renal Transplant Patients

Sirolimus (Rapammune®, rapamycin, RAPA) is a potent immunosuppressive drug that reduces renal transplant rejection. Hyperlipidemia is a significant side effect of sirolimus treatment, and frequently leads to cardiovascular disease. This study was undertaken to determine the repeatability, reversibility, and dose dependence of the plasma lipid and apolipoprotein altering effects of sirolimus, and to elucidate the mechanism by which sirolimus induces hypertriglyceridemia in some renal transplant patients. Six patients with renal allografts maintained on cyclosporine A and prednisone were selected on the basis of their previous hyperlipidemic response to short term (14 days) sirolimus administration. For longer-term treatment, each patient was started on 10 mg/day sirolimus and continued as tolerated for 42 days to reinduce hyperlipidemia. Timed blood samples were analyzed for lipid, apolipoprotein, and sirolimus levels. During sirolimus administration, mean total plasma cholesterol increased from 214 mg/dl to 322 mg/dl (+50%; range 25–92%); LDL-cholesterol levels followed a similar pattern. Mean triglyceride level rose from 227 to 432 mg/dl (+95%; range 9–254%). ApoB-100 concentration rose from 124 to 160 mg/dl (+28%; P < 0.05). ApoC-III level increased from 28.9 to 55.5 mg/dl, +92%; (P < 0.013). These lipid and apolipoprotein changes were found to be repeatable, reversible, and dose dependent. [13C4]palmitate metabolic studies in four patients with hypertriglyceridemia indicated that the free fatty acid pool was expanded by sirolimus treatment (mean = 42.3%). Incorporation of [13C4]palmitate into triglycerides of VLDL, IDL, and LDL was decreased 38.3%, 42,1%, and 38.4%, respectively, by sirolimus treatment of these patients.These results suggest that sirolimus alters the insulin signaling pathway so as to increase adipose tissue lipase activity and/or decrease lipoprotein lipase activity, resulting in increased hepatic synthesis of triglyceride, increased secretion of VLDL, and increased hypertriglyceridemia.

Cardioprotective Effects of Diet with Different Grains on Lipid Profiles and Antioxidative System in Obesity-Induced Rats

2012 ◽  
Vol 82 (2) ◽  
pp. 85-93 ◽  
Author(s):  
Y. Kim ◽  
H. Shin ◽  
S. Lee
Keyword(s):  
Aortic Wall ◽  
Plasma Lipids ◽  
Antioxidant Activities ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Thiobarbituric Acid ◽  
Lipid Profiles ◽  
Dietary Lipids ◽  
Male Rats

In the present study, the nutritional quality of four grains including adlay (AD), buckwheat (BW), glutinous barley (GB), and white rice (WR) were evaluated in terms of plasma lipid parameters, gut transit time, and thickness of the aortic wall in rats. The rats were then raised for 4 weeks on the high-fat diet based on the American Institute of Nutrition-93 (AIN-93 G) diets containing 1 % cholesterol and 20 % dietary lipids. Forty male rats were divided into 4 groups and raised for 4 weeks with a diet containing one of the following grains: WR, AD, BW, or WB. The level of thiobarbituric acid-reactive substances (TBARS) in liver was shown to be higher in rats by the order of those fed WR, AD, GB, and BW. This indicates that other grains decreased oxidative stress in vivo more than WR. The superoxide dismutase, glutathione, glutathione peroxidase, and glutathione reductase levels in the AD, BW, and GB groups were significantly higher than those in the WR group (p < 0.05). Plasma lipid profiles differed significantly according to grain combination, and decreased aortic wall thickness was consistent with the finding of decreased plasma low-density lipoprotein cholesterol (LDL-C) (p < 0.05) and increased high-density lipoprotein (HDL-C) in rats fed AD, BW, and GB (p < 0.001). The antioxidant and hypolipidemic capacities of grains are quite high, especially those of adlay, buckwheat, and glutinous barley. In conclusion, this study has demonstrated that the whole grains had a cardioprotective effect. This effect was related to several mechanisms that corresponded to lowering plasma lipids, decreasing TBARS, and increasing antioxidant activities.

The Effect of n-3 Fatty Acids on Lipids and Haemostasis in Patients with Type lla and Type IV Hyperlipidaemia

1989 ◽  
Vol 62 (02) ◽  
pp. 797-801 ◽  
Author(s):  
E Berg Schmidt ◽  
E Ernst ◽  
K Varming ◽  
J O Pedersen ◽  
J Dyerberg
Keyword(s):  
Fatty Acids ◽  
Plasma Lipids ◽  
Plasma Cholesterol ◽  
Hdl Cholesterol ◽  
Apolipoprotein A1 ◽  
Type Iv ◽  
Before And After ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen

SummaryPlasma lipids and haemostasis were investigated in 17 patients with hyperlipidaemia before and after 6 weeks supplementation with 6 g n-3 fatty acids. Nine of the patients had type IIa and 8 had type IV hyperlipidaemia. No effect on plasma cholesterol, LDL- or HDL-cholesterol were seen, but plasma triglycerides decreased after n-3 supplementation. Apolipoprotein B increased and apolipoprotein A1 decreased after the oil supplement. The bleeding time was prolonged, but platelet aggregation was unaltered by n-3 fatty acids. Protein C activity increased in type II a and decreased in type IV after the supplement. Fibrinolysis was markedly depressed while von Willebrand factor antigen was reduced after intake of n-3 fatty acids.

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