Fatty Acid Composition Of Plasma Lipids Research Articles

Plasma lipid fatty acid composition, desaturase activities and insulin sensitivity in Amerindian women

Background and aimsTwo Amerindian populations – Shuar women living in the Amazonian rain forest under traditional conditions and urbanized women in a suburb of Lima were studied. The fatty acid composition in plasma lipids and the relationships between fatty acid composition and metabolic variables were studied, as well as in a reference group of Swedish women. Methods and resultsFasting plasma was used for analyses of glucose, insulin, leptin and fatty acid composition. Women in Lima had more body fat, higher fasting insulin and leptin and lower insulin sensitivity than the Shuar women, who had insulin sensitivity similar to Swedish women. Shuar women had very high proportions (mean; SD) of palmitoleic (13.2; 3.9%) and oleic (33.9; 3.7%) acids in the plasma cholesteryl esters with very low levels of linoleic acid (29.1; 6.1 3%), as expected on a low fat, high carbohydrate diet. The estimated activity of delta 9 (SCD-1) desaturase was about twice as high in the Shuar compared with Lima women, suggesting neo lipogenesis, while the delta 5 desaturase activity did not differ. The Lima women, as well as the Swedish, showed strong positive correlations between SCD-1 activity on the one hand and fasting insulin and HOMA index on the other. These associations were absent in the Shuar women. ConclusionsThe high SCD-1 activity in the Shuar women may reflect increased lipogenesis in adipose tissue. It also illustrates how a low fat diet rich in non-refined carbohydrates can be linked to a good metabolic situation.

Whole-body synthesis-secretion rates of long-chain n-3 PUFAs from circulating unesterified α-linolenic acid in unanesthetized rats

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), long-chain n-3 PUFAs important for brain and heart function, can be obtained from dietary fish products or by liver synthesis from alpha-linolenic acid (alpha-LNA). Their daily human dietary requirements are not clear, and their liver synthesis rates in humans and nonhumans are unknown. We estimated whole-body (presumably liver) synthesis rates in unanesthetized rats by infusing [U-(13)C]alpha-LNA intravenously for 2 h and measuring labeled and unlabeled n-3 PUFA in arterial plasma using negative chemical ionization GC-MS. Newly synthesized esterified [(13)C]DHA, [(13)C]EPA, and [(13)C]docosapentaenoic acid (DPA) appeared in arterial plasma after 60 min of infusion, then their concentrations rose in an S-shaped manner. Esterified concentration x plasma volume data were fit with a sigmoidal equation, whose peak first derivatives provided synthesis rates of unlabeled EPA, DPA, and DHA equal to 8.40, 6.27, and 9.84 mumol/day, respectively. The DHA synthesis rate exceeded the published daily rat brain DHA consumption rate by 30-fold, suggesting that liver synthesis from alpha-LNA could maintain brain DHA homeostasis were DHA absent from the diet. This stable isotope infusion method could be used to quantify whole-body DHA synthesis rates in human subjects.

Hepatic de Novo Lipogenesis in Stable Low‐Birth‐Weight Infants During Exclusive Breast Milk Feedings and During Parenteral Nutrition

Low-birth-weight (LBW) infants have high energy requirements and are dependent on high fat intake to maintain adequate postnatal growth. Fat energy is transported in plasma as triglycerides, which are either derived from the diet or from de novo lipogenesis (DNL). It is our hypothesis that DNL plays an important physiologic role in adapting to exclusive breast milk (EBM) feeding or to parenteral nutrition (PN). We studied hepatic de novo lipogenesis in 14 LBW (<34-week gestation) appropriate for gestational age and receiving either EBM feedings or full PN support. Stable isotope tracer [2-(13)C] acetate was administered for 72 hours to achieve an estimated 10% enrichment of daily fat intake. Fatty acids were extracted from plasma for gas chromatography-mass spectrometry analyses. Percent new synthesis of palmitate was 13.1% +/- 2.5% in the EBM group and 14.9% +/- 0.7% in the PN group (NS), stearate was 11.1% +/- 2.7% in the EBM group and 10.6% +/- 14% in the PN group (NS) and cholesterol was 12.7% +/- 2.1% in the EBM group and 17.4% +/- 4.6% in the PN group (NS) after 72 hours of tracer administration (mean +/- SEM). The plasma lipid fatty acid composition in palmitate, oleate, and stearate with intake of 3.6 +/- 0.6 g/kg/d of IV lipids (ILs) was similar to EBM-feeding infants taking 6.3 +/- 0.13 g/kg/d of fat. De novo lipogenesis is active in stable LBW infants maintaining standard postnatal growth. Hepatic DNL permits newborn infants to meet the fat energy needs of peripheral tissues for growth and storage and to maintain plasma fatty acid composition in adaptation to different dietary fat intake.

Long-chain conversion of [13C]linoleic acid and α-linolenic acid in response to marked changes in their dietary intake in men

We studied the long-chain conversion of [U-13C]alpha-linolenic acid (ALA) and linoleic acid (LA) and responses of erythrocyte phospholipid composition to variation in the dietary ratios of 18:3n-3 (ALA) and 18:2n-6 (LA) for 12 weeks in 38 moderately hyperlipidemic men. Diets were enriched with either flaxseed oil (FXO; 17 g/day ALA, n=21) or sunflower oil (SO; 17 g/day LA, n=17). The FXO diet induced increases in phospholipid ALA (>3-fold), 20:5n-3 [eicosapentaenoic acid (EPA), >2-fold], and 22:5n-3 [docosapentaenoic acid (DPA), 50%] but no change in 22:6n-3 [docosahexanoic acid (DHA)], LA, or 20:4n-6 [arachidonic acid (AA)]. The increases in EPA and DPA but not DHA were similar to those in subjects given the SO diet enriched with 3 g of EPA plus DHA from fish oil (n=19). The SO diet induced a small increase in LA but no change in AA. Long-chain conversion of [U-13C]ALA and [U-13C]LA, calculated from peak plasma 13C concentrations after simple modeling for tracer dilution in subsets from the FXO (n=6) and SO (n=5) diets, was similar but low for the two tracers (i.e., AA, 0.2%; EPA, 0.3%; and DPA, 0.02%) and varied directly with precursor concentrations and inversely with concentrations of fatty acids of the alternative series. [13C]DHA formation was very low (<0.01%) with no dietary influences.

Fatty acid balance studies in preterm infants fed formula milk containing long‐chain polyunsaturated fatty acids (LCP) II

A milk formula (Prematil‐LCP) containing long‐chain polyunsaturated fatty acids (LCP) and with a fatty acid profile closely resembling breast milk has recently been introduced for preterm infants. A double‐blind randomized controlled trial was performed comparing fatty acid absorption from Prematil‐LCP (n= 10) and standard Prematil (n= 10). Formula‐fed preterm infants underwent 3 d fat balances (once full enteral feeds were established) along with a parallel human milk fed group (n= 11). Plasma samples were taken on the last day. Median total fat excretion (absorption, %) was 2.34 g kg (82.0), 2.64 g kg (82.9) and 1.65 g kg (87.8) with Prematil, Prematil‐LCP and human milk feeding, respectively. This reflected differences in the excretion and absorption of long‐chain saturated fatty acids. All groups excreted detectable LCP. LCP disappearance was higher in infants fed human milk than in those fed Prematil‐LCP, particularly for n‐6 LCP (p &lt;0:01). Nevertheless, excreted LCP equated to &lt;30% dietary intake, with Prematil‐LCP feeding. Plasma lipid fatty acid composition reflected differences in dietary LCP intake.

Effect of Gemfibrozil on Fatty Acids in Lipid Fractions of Plasma From Patients with Hypertriglyceridemia

The fatty acid composition of plasma triglycerides, phospholipids, and cholesterol esters have been studied during gemfibrozil (G)-induced lipid-lowering treatment in six patients with hypertriglyceridemia. Gemfibrozil caused significant plasma triglyceride reductions from 776 +/- 573 to 226 +/- 82 mg/dL (P < .001). Gemfibrozil therapy also caused significant changes in the plasma lipid fatty acid composition, mainly by increasing palmitoleic acid (16:1) in triglycerides (2.1-5.6%) and cholesterol esters (2.2-3.7%), concomitant with the significant decrease in the content of the linoleic acid (18:2) in phospholipids (20.1-16.0%) and triglycerides (18.0-15.2%). The ratio of unsaturated fatty acids (20:3 + 20:4/18:2) was increased in the phospholipid fraction. These findings support a G effect on the desaturation of fatty acids in patients with hypertriglyceridemia. Because fatty acid composition was significantly altered by G, those biologic systems dependent on the pattern of fatty acids may be modified in clinical important ways.

Maintenance of lower proportions of ( n − 6) eicosanoid precursors in phospholipids of human plasma in response to added dietary ( n − 3) fatty acids

Competition between the ( n − 3) and ( n − 6) types of highly unsaturated fatty acids can diminish the abundance of ( n − 6) eicosanoid precursors in a tissue, which in turn can diminish the intensity of tissue responses that are mediated by ( n − 6) eicosanoids. The mixture of 20- and 22-carbon highly unsaturated fatty acids maintained in the phospholipids of human plasma is related to the dietary intake of 18:2 ( n − 6) and 18:3 ( n −3) by empirical hyperbolic equations in a manner very similar to the relationship reported for laboratory rats (Lands, W.E.M., Morris, A. and Libelt, B. (1990) Lipids 25, 505–516). Analytical results from volunteers ingesting self-selected diets showed an inter-individual variance for the proportion of ( n − 6) eicosanoid precursors in the fatty acids of plasma phospholipids of about 5%, but the variance among multiple samples taken from the same individual throughout the day was less (about 3%), closer to the experimental variance of the analytical procedure (about 1%). The reproducibility of the results makes it likely that analysis of fatty-acid composition of plasma lipids from individuals will prove useful in estimating the diet-related tendency for severe thrombotic, arthritic of other disorders that are mediated by ( n − 6) eicosanoids. Additional constants and terms were included in the equations to account for the effects of 20- and 22-carbon highly unsaturated ( n − 3) fatty acids in the diet. A lower constant for the 20- and 22-carbon ( n − 3) fatty acids compared to that for the 18-carbon ( n − 3) fatty acid in decreasing the ability of dietary 18:2 ( n − 6) to maintain 20:4 ( n − 6) in tissue lipids confirmed the greater competitive effectiveness of the more highly unsaturated n − 3 fatty acids in the elongation/ desaturation process. Also, a lower constant for direct incorporation of 20-carbon fatty acids of the n − 6 vs. the n − 3 type indicated a greater competitive effectiveness of 20:4 ( n − 6) relative to 20:5 ( n − 3) in reesterification after release from tissue lipids. The equations may be used in reverse to estimate the dietary intakes of the ( n − 3) and ( n − 6) fatty acids by using the composition of the fatty acids that had been maintained in plasma lipids.

Red blood cell fatty acids in multiple sclerosis.

The fatty acid (FA) composition of each phospholipid constituent of the red blood cells (RBC) was analyzed, by thin-layer and gas chromatography techniques, in 61 multiple sclerosis (MS) patients and 61 normal subjects, in whom the plasma lipid FA composition had previously been studied. The MS patients showed a significant decrease in the proportions of linoleic and arachidonic acids in most phospholipids, with a compensatory increase of saturated FA. Correlations between FA percentages in plasma and cell lipids demonstrated abnormalities in the MS patients, suggestive of a disturbance in the exchange between these compartments. The alterations reported in plasma and RBC in the MS patients are consistent with a relative deficiency of essential FA.

Effect of linseed oil ingestion on plasma lipid fatty acid composition and platelet aggregability in healthy volunteers

Eight healthy volunteers ingested 60 ml linseed oil over a period of six weeks. Icosapentaenoic acid increased in plasma triglycerides (TG), phospholipids (PL) and cholesteryl esters (CE) but did not exceed mean values of 2%. α-Linolenic acid rose markedly in TG, linoleic acid decreased in TG and CE, and arachidonic acid decreased in PL and CE. Two additional subjects on a similar regimen underwent blood platelet aggregability tests by the collagen threshold procedure. In both cases a striking decrease in platelet sensitivity to collagen was observed. The results show that linseed oil affects the polyunsaturated fatty acid profile of plasma lipids and suggest a possible alteration of platelet aggregability.

Influence of Trans-9-, Trans-12-, and CIS-12-octadecenoic acid isomers on fatty acid composition of human plasma lipids

Deuterium-labeled trans-9-, trans-12-, and cis-12-octadecenoic acid isomers were fed to young adult male subjects. Incorporation of these deuterated isomeric fats into plasma lipids was followed by GC-MS, and the influence of the isomers on plasma lipid fatty acid composition was determined. The 18:2 and 20:4 levels in the phospholipid fractions initially decreased and 16:0, 18:0 and 18:1 levels increased as the deuterated 12-octadecenoic acids were incorporated. A smaller reverse effect was found for 16:0 and 18:2 acids when trans-9-octadecenoic acid was fed. Fatty acid composition of phosphatidylcholine returned to near baseline values as the monoenoic acid isomers levels began to decrease. Initially after feeding 12–18:1, plasma triglyceride 16:0 levels increased and 18:2 levels decreased. The percentage of 18:2 continued to decrease after the 12-octadecenoic acid level began to decrease. Presumably this occurred because plasma tryglycerides continued to supply phospholipids with 18:2. Fluctuation of both the 16:0 and 18:2 fatty acid percentages in plasma tryglyceride samples were correlated with trans-9-octadecenoic acid content. Only low levels of all three octadecenoic acid isomers were incorporated into the plasma cholesteryl ester fraction, and none of the isomers had an effect on cholesteryl ester fatty acid composition.

Effects of bezafibrate on the serum lipoprotein lipid and apolipoprotein composition, lipoprotein triglyceride removal capacity and the fatty acid composition of the plasma lipid esters

Bezafibrate has been shown to effectively reduce elevated levels of very low density lipoprotein (VLDL) in hypertriglyceridaemia. It has also been claimed to be particularly effective in increasing high density lipoprotein (HDL) concentrations. In the present study 15 hypertriglyceridaemic patients (9 type IIB, 1 type III and 5 type IV) were investigated before and after 2 months' treatment with bezafibrate (600 mg daily) in an effort to clarify further the effects of the drug on lipoprotein metabolism. The serum triglycerides decreased by 46% ( P < 0.001) corresponding to a significant reduction of both the VLDL (−43%, P < 0.001) and the low density lipoprotein (LDL) (−27%, P < 0.05) triglycerides. The serum cholesterol decreased by 13% ( P < 0.001), mainly due to reduction of the VLDL cholesterol (−51%, P < 0.001). There was no significant reduction of the LDL cholesterol in the whole group (−10%, n.s.). However, if only the patients with hypercholesterolaemia were considered, there was a significant reduction of LDL cholesterol by 19% ( P < 0.01). HDL triglycerides and HDL cholesterol increased by 20% ( P < 0.05) and 22% ( P < 0.001) respectively. While the concentration of apolipoprotein (apo) B decreased by 15% ( P < 0.01) there were significant increases of apo A-I (+14%, P < 0.001) and apo A-II (+30%, P < 0.001) analogous to the increase of HDL lipid concentration. However, the ratio between apo A-I and apo A-II decreased significantly during therapy (−12%, P < 0.001) indicating that the increase of HDL may have preferentially affected the HDL-3 fraction. There were highly significant reductions of both the ratio between LDL and HDL cholesterol (−24%, P < 0.001) and the ratio between apo B and apo A-I (−25%, P < 0.001), changes which should be favourable with regard to atherogenicity. Significant increases of both the plasma post-heparin lipoprotein lipase activity (+20%, P < 0.001) and the fractional removal rate (K 2) at the intravenous fat tolerance test (+30%, P < 0.001) indicate that one of the mechanisms behind the effects of the drug on lipoprotein metabolism may be an increased removal of circulating triglyceride-rich lipoproteins. Bezafibrate treatment caused significant changes in the plasma lipid fatty acid composition, mainly by increasing the mono-unsaturated fatty acids (palmitoleate and oleate) concomitant with a significant decrease in the content of linoleate. Very similar changes have been recorded during clofibrate treatment. The mechanisms behind these changes as well as their significance are at present obscure.

Supplementation with vitamin E in hyperlipidemic patients treated with diet and clofibrate. Effects on serum lipoprotein concentrations, plasma fatty acid composition and adipose tissue lipoprotein lipase activity

Twelve hyperlipidemic patients on long term treatment with a lipid lowering diet enriched in polyunsaturated fatty acids and with clofibrate were supplemented with vitamin E (400 mg/day). The effect on serum lipoprotein concentration, plasma lipid fatty acid composition, and adipose tissue lipoprotein lipase activity was studied. No additional lipid-lowering effect was registered during a treatment period of 4 months. A slight increase in total serum cholesterol concentration and in high density lipoprotein concentration was probably attributable to seasonal variations in serum lipoprotein concentrations. No major changes of fatty acid composition in plasma cholesteryl esters or triglycerides were recorded. However, an increased relative amount of arachidonic acid and a reduced amount of palmitic acid in the plasma phospholipids after 2 months was possibly caused by the vitamin E therapy.