Metabolic effects of intravenous LCT or MCT/LCT lipid emulsions in preterm infants

Most lipid emulsions for parenteral feeding of premature infants are based on long-chain triacylglycerols (LCTs), but inclusion of medium-chain triacylglycerols (MCTs) might provide a more readily oxidizable energy source. The influence of these emulsions on fatty acid composition and metabolism was studied in 12 premature neonates, who were randomly assigned to an LCT emulsion (control) or an emulsion with a mixture of MCT and LCT (1:1). On study day 7, all infants received [13C]linoleic (LA) and [13C]alpha-linolenic acid (ALA) tracers orally. Plasma phospholipid (PL) and triacylglycerol (TG) fatty acid composition and 13C enrichments of plasma PL fatty acids were determined on day 8. After 8 days of lipid infusion, plasma TGs in the MCT/LCT group had higher contents of C8:0 (0.50 +/- 0.60% vs. 0.10 +/- 0.12%; means +/- SD) and C10:0 (0.66 +/- 0.51% vs. 0.15 +/- 0.17%) than controls. LA content of plasma PLs was slightly lower in the MCT/LCT group (16.47 +/- 1.16% vs. 18.57 +/- 2.09%), whereas long-chain polyunsaturated derivatives (LC-PUFAs) of LA and ALA tended to be higher. The tracer distributions between precursors and products (LC-PUFAs) were not significantly different between groups. Both lipid emulsions achieve similar plasma essential fatty acid (EFA) contents and similar proportional conversion of EFAs to LC-PUFAs. The MCT/LCT emulsion seems to protect EFAs and LC-PUFAs from beta-oxidation.     

Trans fatty acids in hydrogenated fat inhibited the synthesis of the polyunsaturated fatty acids in the phospholipid of arterial cells

Our hypothesis that the trans fatty acids in hydrogenated fat inhibited the synthesis of polyunsaturated fatty acids in the phospholipid of arterial cells was tested with five groups each with six pregnant porcine fed from d 35 of gestation and during lactation. The basal diet contained 2% corn oil (control). The other four diets included the control + 10% butter or 10% hydrogenated fat plus two levels of Mg. Plasma, milk and aortic phospholipid fatty acids, phospholipid composition and calcium content of the aorta from the piglets were determined. At 48 +/- 2 d of age, the aorta phospholipid of piglets from porcine fed hydrogenated fat contained a significantly higher concentration of linoleic acid, less arachidonic acid, and less long chain polyunsaturated fatty acid (PUFA) than did piglets from porcine fed either butterfat or the control diet. Mg had no effect. These changes in composition in piglets from porcine fed hydrogenated fat indicate that trans fat inhibits the metabolic conversion of linoleic acid to arachidonic acid and to other n-6 PUFA. The aortic calcium content data showed a significant interaction of calcium concentration with age. We concluded: 1) that dietary trans fat perturbed essential fatty acid (EFA) metabolism which led to changes in the phospholipid fatty acid composition in the aorta, the target tissue of atherogenesis, 2) this inhibition of EFA to PUFA by the isomeric fatty acids in hydrogenated fat is a risk factor in the development of coronary heart disease.     

Distribution of fatty acids from dietary oils into phospholipid classes of triacylglycerol-rich lipoproteins in healthy subjects

Several studies have suggested that lipoprotein metabolism can be affected by lipoprotein phospholipid composition. We investigated the effect of virgin olive oil (VOO) and high-oleic sunflower oil (HOSO) intake on the distribution of fatty acids in triacylglycerols (TG), cholesteryl esters (CE) and phospholipid (PL) classes of triacylglycerol-rich lipoproteins (TRL) from normolipidemic males throughout a 7 h postprandial metabolism. Particularly, changes in oleic acid (18:1n-9) concentration of PL were used as a marker of in vivo hydrolysis of TRL external monolayer. Both oils equally promoted the incorporation of oleic acid into the TG and CE of postprandial TRL. However, PL was enriched in oleic acid (18:1n-9) and n-3 polyunsaturated fatty acids (PUFA) after VOO meal, whereas in stearic (18:0) and linoleic (18:2n-6) acids after HOSO meal. We also found that VOO produced TRL which PL 18:1n-9 content was dramatically reduced along the postprandial period. We conclude that the fatty acid composition of PL can be a crucial determinant for the clearance of TRL during the postprandial metabolism of fats.     

Metabolism of n-3 polyunsaturated fatty acids and modification of phospholipids in cultured rabbit aortic smooth muscle cells

The metabolism of the linolenic acid family (n-3) of fatty acids, e.g., linolenic, eicosapentaenoic, and docosahexaenoic acids, in cultured smooth muscle cells from rabbit aorta was compared to the metabolism of linoleic and arachidonic acids. There was a time-dependent uptake of these fatty acids into cells for 16 hr (arachidonic greater than docosahexaenoic, linoleic, eicosapentaenoic greater than linolenic), and the acids were incorporated mainly into phospholipids and triglycerides. Eicosapentaenoic and arachidonic acids were incorporated more into phosphatidylethanolamine and phosphatidylinositol plus phosphatidylserine and less into phosphatidylcholine than linolenic and linoleic acids. Docosahexaenoic acid was incorporated into phosphatidylethanolamine more than linolenic and linoleic acids and into phosphatidylinositol plus phosphatidylserine less than eicosapentaenoic and arachidonic acids. Added linolenic acid accumulated mainly in phosphatidylcholine and did not decrease the arachidonic acid content of any phospholipid subfraction. Elongation-desaturation metabolites of linoleic acid did not accumulate. Cells treated with eicosapentaenoic acid accumulated both eicosapentaenoic and docosapentaenoic acids mainly in phosphatidylethanolamine and the arachidonic acid content was decreased. Added docosahexaenoic acid accumulated mainly in phosphatidylethanolamine and decreased the content of both arachidonic and oleic acids. The following conclusions are drawn from these results. The three n-3 fatty acids are utilized differently in phospholipids. The arachidonic acid content of phospholipids is reduced by eicosapentaenoic and docosahexaenoic acids, but not by linolenic acid. Smooth muscle cells have little or no desaturase activity, but have significant elongation activity for polyunsaturated fatty acids.     

Studies on polyenoic acid incorporation into human platelet lipid stores: interactions with linoleic and arachidonic acids

Several polyunsaturated fatty acids (C18-C22 acids) have been compared in their uptake by human platelets and their acylation into glycerophospholipid subclasses. This was also studied in the presence of linoleic and/or arachidonic acids, the main fatty acids of plasma free fatty acid pool. Amongst C20 fatty acids, dihomogamma linolenic acid (20:3(n-6)), 5,8,11-icosatrienoic acid (20:3(n-9)) and arachidonic acid (20:4(n-6)) were better incorporated. The uptake of 5,8,11,14,17-icosapentaenoic acid (20:5(n-3)) was significantly lower and comparable to that of C22 fatty acids (7,10,13,16-docosatetraenoic acid (22:4(n-6)) and 4,7,10,13,16,19-docosahexaenoic acid (22:6(n-3)) and linoleic acid (18:2(n-6)). In this respect, linolenic acid (18:3(n-3)) appeared the poorest substrate. The bulk of each acid was acylated into glycerophospholipids although the presence of linoleic and/or arachidonic acids diverted a part towards neutral lipids. This was prominent for 18:3(n-3) and C22 fatty acids. The glycerophospholipid distribution of each acid differed substantially and was not affected by the presence of linoleic and or arachidonic acids, except for 18:3(n-3) and 22:6(n-3) that were strongly diverted towards phosphatidylethanolamine (PE) at the expense of phosphatidylcholine (PC). The main features were an efficient acylation of 20:3(n-9) into phosphatidylinositol (PI) followed by 20:3(n-6) and 20:4(n-6), then by 20:5(n-3) and 22:4(n-6), and finally 22:6(n-3) and C18 fatty acids. This was reciprocal to the acylation into PE and to a lesser extent into PC which remained the main storage species in all cases. We conclude that human platelets may exhibit a certain specificity for taking up polyunsaturated fatty acids both in terms of total uptake and glycerophospholipid subclass distribution. Also the presence of polyunsaturated fatty acids of normal plasma, like linoleic and arachidonic acids, may interact specifically with such an uptake and distribution.     

Dietary long-chain fatty acids and visual response in malnourished nursing infants

Polyunsaturated fatty acids (PUFAs) derived from essential fatty acids (EFAs) play an important role in prenatal visual and neural development. Protein-energy malnutrition affects PUFA supply, and hence the synthesis of structural lipids during growth. Recently, some physiological studies reported abnormalities in the visual function of formula-fed infants relative to breast-fed infants. The purpose of our study was to assess whether fatty acid composition of the malnourished infant diet modifies the visual function and erythrocyte phospholipid fatty acid composition. Three groups of full-term malnourished infants were selected. Two groups received commercial formulas. One of them supplied linoleic and alpha -linolenic acid: Formula I (FI), and the other supplied, in addition, long-chain PUFAs from n-3 and n-6 series: Formula II (FII). A reference group of breast-fed infants was also enrolled. Visual function was assessed using full-field flash electroretinography, and the erythrocyte phospholipid fatty acid composition was determined by gas-liquid chromatography. Those infants receiving the supplemented formula (FII) exhibited a similar retinal function to that of breast-fed infants. However, normal results were not achieved when infants were fed on the FI formula. In all groups, the results were correlated with the proportion of docosahexaenoic acid in erythrocyte phospholipid fatty acid composition. We conclude that in malnourished infants a nutrient formula enriched with long-chain fatty acids of n-6 and n-3 series could be helpful to achieve an erythrocyte fatty acid pattern and a visual function similar to that obtained in breast-fed infants.     

Sex differences in the metabolism of essential fatty acids studied in isolated rat liver cells

The triacylglycerol synthesis from exogenous linoleic acid (18:2(n-6], linolenic acid (18:3(n-3], dihomogammalinolenic acid (20:3(n-6], eicosapentaenoic acid (20:5(n-3] and oleic acid (18:1(n-9] was observed to be significantly increased in isolated liver cells from female rats compared with males. The rate of fatty acid oxidation and phospholipid biosynthesis was concomitantly more important in male cells. With the C22-polyenoic fatty acids, adrenic acid (22:4(n-6] and docosahexaenoic acid (22:6(n-3), only a minor sex-related difference in fatty acid metabolism was found.     

Glycine uptake by cultured human Y79 retinoblastoma cells: effect of changes in phospholipid fatty acid unsaturation

Glycine uptake was investigated in cultured Y79 retinoblastoma cells containing different degrees of phospholipid fatty acid unsaturation. The modifications were produced by growing the retinoblastoma cells in medium supplemented with various unsaturated fatty acids. Glycine was taken up by the retinoblastoma cells through two kinetically distinguishable process. The high-affinity system is totally dependent upon extracellular Na+ and partially dependent upon Ca2+. Of the glycine taken up by retinoblastoma cells, 85-90% remains as free intracellular glycine and less than 30% is incorporated into cellular protein. When the cells are grown in a medium containing 10% fetal bovine serum as the only source of fatty acids, the phospholipids contained 23% polyunsaturated fatty acids. Under these conditions the high-affinity system has a K'm of 34.2 +/- 3.7 micrometers and a V'max of 91.2 +/- 16.2 pmol min-1 mg protein -1. The low-affinity system has a K'm of 2.7 +/- 0.4 mM and a V'max of 4.1 +/- 0.5 nmol min-1 mg protein-1. When the polyunsaturated fatty acid content of the phospholipids was increased by supplementing the medium with linolenic or docosahexaenoic acids (n-3 polyunsaturates) or linoleic or arachidonic acids (n-6 polyunsaturates), the K'm and V'max of the high-affinity glycine uptake system were increased three- to fourfold. By contrast, supplementing the medium with oleic acid, and n-9 monounsaturate, did not significantly alter the K'm or V'max for glycine uptake. The results with this model system suggest that one of the effects of the high polyunsaturated fatty acid content normally present in neural cell membranes may be a modulation of the high-affinity transport system so that it functions more efficiently in regulating glycine uptake.     

Maternal dietary fat alters amniotic fluid and fetal intestinal membrane essential n-6 and n-3 fatty acids in the rat

We investigated whether maternal fat intake alters amniotic fluid and fetal intestine phospholipid n-6 and n-3 fatty acids. Female rats were fed a 20% by weight diet from fat with 20% linoleic acid (LA; 18:2n-6) and 8% alpha-linolenic acid (ALA; 18:3n-3) (control diet, n = 8) or 72% LA and 0.2% ALA (n-3 deficient diet, n = 7) from 2 wk before and then throughout gestation. Amniotic fluid and fetal intestine phospholipid fatty acids were analyzed at day 19 gestation using HPLC and gas-liquid chromotography. Amniotic fluid had significantly lower docosahexaenoic acid (DHA; 22:6n-3) and higher docosapentaenoic acid (DPA; 22:5n-6) levels in the n-3-deficient group than in the control group (DHA: 1.29 +/- 0.10 and 6.29 +/- 0.33 g/100 g fatty acid; DPA: 4.01 +/- 0.35 and 0.73 +/- 0.15 g/100 g fatty acid, respectively); these differences in DHA and DPA were present in amniotic fluid cholesterol esters and phosphatidylcholine (PC). Fetal intestines in the n-3-deficient group had significantly higher LA, arachidonic acid (20:4n-6), and DPA levels; lower eicosapentaenoic acid (EPA; 20:5n-3) and DHA levels in PC; and significantly higher DPA and lower EPA and DHA levels in phosphatidylethanolamine (PE) than in the control group; the n-6-to-n-3 fatty acid ratio was 4.9 +/- 0.2 and 32.2 +/- 2.1 in PC and 2.4 +/- 0.03 and 17.1 +/- 0.21 in PE in n-3-deficient and control group intestines, respectively. We demonstrate that maternal dietary fat influences amniotic fluid and fetal intestinal membrane structural lipid essential fatty acids. Maternal dietary fat can influence tissue composition by manipulation of amniotic fluid that is swallowed by the fetus or by transport across the placenta.     

Polyunsaturated fatty acid biosynthesis from [1-14C]20:3 n-6 acid in rat cultured Sertoli cells. Linoleic acid effect

Primary culture is a suitable system to study lipid metabolism and polyunsaturated fatty acid biosynthesis. Sertoli cell-enriched preparations were used to determine the fatty acid composition after 5 and 7 days in culture (serum free) as well as the uptake and metabolism of [1-14C]eicosa-8,11,14-trienoic acid. The addition of unlabeled linoleic acid (0.2 and 2.0 microg/ml) was also evaluated. Fatty acid methyl esters derived from cellular lipids were analyzed by gas liquid chromatography and radiochromatography. After 5 days in culture, cells had significantly less 18:2, 20:4, 22:5 and 24:5 and more 18:3, 20:3, 22:4 and 24:4 n-6 fatty acids than non-cultured cells. On day 7, an additional increment in 22:4 n-6 and a decrease in linoleic, gamma-linoleic and 24:4 n-6 fatty acids were observed. The presence of linoleic acid (low dose) produced a significant decrease in saturated and monounsaturated acids and an increase in 18:2, 20:4 and 22:5 n-6 fatty acids. At a high concentration almost all fatty acids belonging to 18:2 n-6 increased significantly. The drop in 20:4 n-6/20:3 n-6 ratio was considered as an indirect evidence of a Delta 5 desaturase activity depression. This assumption was corroborated by studying the transformation of [1-14C]eicosa-8,11,14-trienoic acid into 20:4, 22:4, 22:5, 24:4 and 24:5 n-6 fatty acids. We conclude that Sertoli cells after 7 days in culture evidenced changes in the fatty acid profile similar to those described under fat deprivation. The addition of linoleic acid reverted this pattern and indicated that the Delta 5 desaturase activity is a limiting step in the polyunsaturated fatty acid biosynthesis.     

Uptake and metabolic conversion of saturated and unsaturated fatty acids in Hep2 human larynx tumor cells

Research on fatty acid metabolism in cultured human larynx tumor cells Hep2 was carried out.The cells were incubated with either a saturated (palmitic) or a polyunsaturated (linoleic, alpha-linolenic and eicosatrienoic (n-6)) radioactive fatty acid (0.66 pM, 24 h). The best incorporation capacity was observed in the linoleic acid followed by alpha-linolenic, palmitic and eicosatrienoic acids. All fatty acids tested were anabolized to higher derivatives within their own family. Palmitic acid was primarily monodesaturated rather than elongated, proving to have a very active A9 desaturase activity.With respect to polyunsaturated acid metabolism, the conversion of alpha-linolenic acid to higher homologs, although better than linoleic acid, occurred far less efficiently than that observed in other non-highly undifferentiated human tumor cells. This impairment in higher polyunsaturated fatty acid biosynthesis, reflected in the low levels of arachidonic acid in the fatty acid composition, would not reside in the A5 desaturation step since Hep2 cells can readily convert eicosatrienoic acid into arachidonic acid. Considering the potential regulatory role of specific polyunsaturated fatty acids in the cell proliferative control, the knowledge of the metabolism of fatty acids in this human tumor cell would be important for designing future experiments in order to clarify the mechanism involved in balance, proliferation and cell death.     

Minor amounts of plasma medium-chain fatty acids and no improved time trial performance after consuming lipids.

Medium-chain triacylglycerols (MCT) have a potential glycogen-saving effect during exercise due to rapid hydrolysis and oxidation. However, studies comparing intake of carbohydrates (CHO) plus 80-90 g MCT with intake of CHO alone have revealed different results. The present study tested performance after consumption of specific structured triacylglycerol, consisting of a mixture of medium-chain fatty acids and long-chain fatty acids, to prevent the adverse effects observed by MCT (pure medium-chain fatty acids) regarding gastrointestinal distress. Seven well-trained subjects cycled 3 h at 55% of maximum O2 uptake during which they ingested CHO or CHO plus specific structured triacylglycerols. Immediately after the constant-load cycling, the subjects performed a time trial of approximately 50-min duration. Breath and blood samples were obtained regularly during the experiment. Fatty acid composition of plasma triacylglycerols, fatty acids, and phospholipids was determined. Performance was similar after administration of CHO plus specific structured triacylglycerol [medium-, long-, and medium-chain fatty acid (MLM)] compared with CHO (50.0 +/- 1.8 and 50.8 +/- 3.6 min, respectively). No plasma 8:0 was detected in the plasma lipid classes, but the amount of phospholipid fatty acids was significantly higher after CHO+MLM compared with CHO intake. The lacking time trial improvement after intake of medium-chain fatty acids might be due to no available 8:0 in the systemic circulation. A higher level of plasma phospholipid fatty acids in the CHO+MLM compared with the CHO group was probably due to endogenous phospholipid release into chylomicrons.     

The effects of unsaturated fatty acids on lipid metabolism in HepG2 cells

We investigated the effects of stearic acid (saturated), oleic acid (monounsaturated), linoleic acid (n-6 polyunsaturated), and alpha-linolenic acid (n-3 polyunsaturated) on lipid metabolism in a hepatocyte-derived cell line, HepG2. HepG2 cells were cultured in medium supplemented with either stearic acid (0.1% w/v), oleic acid (0.1% v/v), linoleic acid (0.1% v/v), or alpha-linolenic acid (0.1% v/v). After 24 h, expression of lipid metabolism-associated genes was evaluated by real-time PCR. Alpha-linolenic acid showed a suppressive effect on the hepatic fatty acid de novo synthesis and fatty acid oxidation pathways, while linoleic acid also showed a tendency to suppress these pathways although the effect was weaker. Moreover, alpha-linolenic acid enhanced the expression of enzymes associated with reactive oxygen species (ROS) elimination. In contrast, oleic acid tended to promote fatty acid synthesis and oxidation. In conclusion, alpha-linolenic acid and linoleic acid may be expected to ameliorate hepatic steatosis by downregulating fatty acid de novo synthesis and fatty acid oxidation, and by upregulating ROS elimination enzymes. Oleic acid had no distinct effects for improving steatosis or oxidative stress.     

The levels of essential unsaturated fatty acids in human milk on the 3rd, 4th, 5th, and 6th days after labour

The composition of fatty acids in human milk lipids was determined in 41 women on the 3rd, 4th, 5th and 6th days after labour by the method of gas chromatography. In these investigations no significant differences were demonstrated in the fatty acids in the lipid fractions between these consecutive days. The level of polyunsaturated fatty acids of the n-6 and n-3 groups was about 11.9-13.6%, including linoleic acid (18:2, n-6) about 7.7-9.8%, and alpha-linolenic acid (18:3, n-3) about 0.7-1%. In the analysis group of n-6 fatty acids the determined acids were: linoleic acid (18:2, n-6), gamma-linolenic acid (18:3, n-6), eicosadienoic acid (20:2, n-6), eicosatrienoic acid (20:3, n-6), arachidonic acid (20:4, n-6), docosahexaenoic acid (22:6, n-6). From the group of n-3 acids the identified ones were: alpha-linolenic acid (18:3, n-3), eicosapentaenoic acid (20:5, n-3), docosapentaenoic acid (22:5, n-3) and docosahexaenoic acid (22:6, n-3). The obtained quotients of fatty acids n-6 through n-3 on the consecutive days were: 7.2:1-7.8:1, indicating a too low level of the n-3 acids in the investigated milk. The acids prevailing in human milk lipids were: oleic (18:1, n-9) and palmitic (16:0) which accounted for 37-39% and 25-26% respectively. The polyunsaturated to saturated fatty acid ratio (P:S) ranged from 0.28 to 0.33.     

Effect of dietary fats on linoleic acid metabolism. A radiolabel study in rats

Effects on the linoleic acid metabolism in vivo of three dietary fats, rich in either oleic acid, trans fatty acids or alpha-linolenic acid, and all with the same linoleic acid content, were investigated in male Wistar rats. After 6 weeks of feeding, the rats were intubated with [1-14C]linoleic acid and [3H]oleic acid. The incorporation of these radiolabels into liver, heart and serum was investigated 2, 4, 8, 24 and 48 h after intubation. The amount of 14C-labelled arachidonic acid incorporated into the liver phospholipid of the group fed the oleic acid-rich diet was significantly higher than that of the other groups. However, compared to the trans fatty acids-containing diet, the oleic acid-rich diet induced only a slightly higher arachidonic acid level in the phospholipid fraction of the tissues as determined by GLC. Dietary alpha-linolenic acid more than halved the arachidonic acid levels. Our results do not support the hypothesis that the delta 6-desaturase system actually determines the polyunsaturated fatty acid levels in tissue lipids by regulating the amount of polyunsaturated fatty acids (e.g., arachidonic acid) synthesized. The biosynthesis of polyunsaturated fatty acids only is not sufficient to explain the complicated changes in fatty acid compositions as observed after feeding different dietary fats.     

How relevant is the ratio of dietary n-6 to n-3 polyunsaturated fatty acids to cardiovascular disease risk? Evidence from the OPTILIP study

PURPOSE OF REVIEW: There has been much debate over the practical utility of the dietary ratio of n-6 to n-3 polyunsaturated fatty acids in optimizing the benefits of n-3 fatty acids (C18-C22) on cardiovascular health. This review examines the supporting evidence from the OPTILIP study within the context of the emerging consensus on the value of this dietary metric. RECENT FINDINGS: The question of whether the ratio of n-6/n-3 polyunsaturated fatty acids or total amounts of dietary polyunsaturated fatty acids is of more importance to cardiovascular health has been addressed recently in a randomly controlled trial (OPTILIP) and in a stable isotope tracer study. These two studies were independently unanimous in concluding that the ratio of n-6/n-3 polyunsaturated fatty acids is of no value in modifying cardiovascular disease risk. The latter study also showed that the absolute amounts of dietary linoleic acid and alpha-linolenic acid are of relevance to the efficiency of conversion of alpha-linolenic acid to eicosapentaenoic acid and docosahexaenoic acid. SUMMARY: This review should help to settle any outstanding controversy over the dietary ratio of n-6/n-3 polyunsaturated fatty acids. It reinforces current recommendations to increase the consumption of preformed eicosapentaenoic acid/docosahexaenoic acid in fish, and supports dietary measures to increase and decrease intakes alpha-linolenic acid and linoleic acid, respectively, to promote the endogenous synthesis of these longer chain n-3 polyunsaturated fatty acids.     

Docosahexaenoic acid synthesis from alpha-linolenic acid is inhibited by diets high in polyunsaturated fatty acids

The conversion of the plant-derived omega-3 (n-3) α-linolenic acid (ALA, 18:3n-3) to the long-chain eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) can be increased by ALA sufficient diets compared to ALA deficient diets. Diets containing ALA above an optimal level result in no further increase in DHA levels in animals and humans. The present study evaluates means of maximizing plasma DHA accumulation by systematically varying both linoleic acid (LA, 18:2n-6) and ALA dietary level. Weanling rats were fed one of 54 diets for three weeks. The diets varied in the percentage of energy (en%) of LA (0.07–17.1 en%) and ALA (0.02–12.1 en%) by manipulating both the fat content and the balance of vegetable oils. The peak of plasma phospholipid DHA (>8% total fatty acids) was attained as a result of feeding a narrow dietary range of 1–3 en% ALA and 1–2 en% LA but was suppressed to basal levels (～2% total fatty acids) at dietary intakes of total polyunsaturated fatty acids (PUFA) above 3 en%. We conclude it is possible to enhance the DHA status of rats fed diets containing ALA as the only source of n-3 fatty acids but only when the level of dietary PUFA is low (<3 en%).     

Significance of lipoxygenase-derived monohydroxy fatty acids in cutaneous biology

The skin displays a highly active metabolism of polyunsaturated fatty acids (PUFA). Dietary deficiency of linoleic acid (LA), an 18-carbon (n-6) PUFA, results in characteristic scaly skin disorder and excessive epidermal water loss. Although arachidonic acid (AA), a 20-carbon (n-6) PUFA, is metabolized via cyclooxygenase pathway into predominantly prostaglandin E2 (PGE2) and PGF2alpha. The 15-lipoygenase is very active in this tissue and catalyzes the transformation of 20-carbon AA into predominantly 15-hydroxyeicosatetraenoic acid (15-HETE). Similarly, the epidermal 15-lipoxygenase also catalyzes the transformation of 18-carbon LA and 20-carbon dihomo-gamma-linolenic acid (DGLA) to 13-hydroxyoctadecadienoic acid (13-HODE) and 15-hydroxyeicosatrienoic acid (15-HETrE), respectively. The monohydroxy fatty acids are incorporated in phospholipids which undergo catalysis to yield substituted-diacylglycerols (13-HODE-DAG) and 15-HETrE-DAG) which exert anti-inflammatory/antiproliferative effects on the skin.     

The influence of n-3 polyunsaturated fatty acids and very low calorie diet during a short-term weight reducing regimen on weight loss and serum fatty acid composition in severely obese women

Polyunsaturated fatty acids of n-3 series (n-3 PUFA) were shown to increase basal fat oxidation in humans. The aim of the study was to compare the effect of n-3 PUFA added to a very low calorie diet (VLCD), with VLCD only during three-week inpatient weight reduction. Twenty severely obese women were randomly assigned to VLCD with n-3 PUFA or with placebo. Fatty acids in serum lipid fractions were quantified by gas chromatography. Differences between the groups were determined using ANOVA. Higher weight (7.55+/-1.77 vs. 6.07+/-2.16 kg, NS), BMI (2.82+/-0.62 vs. 2.22+/-0.74, p<0.05) and hip circumference losses (4.8+/-1.81 vs. 2.5+/-2.51 cm, p<0.05) were found in the n-3 group as compared to the control group. Significantly higher increase in beta-hydroxybutyrate was found in the n-3 group showing higher ketogenesis and possible higher fatty acid oxidation. The increase in beta-hydroxybutyrate significantly correlated with the increase in serum phospholipid arachidonic acid (20:4n-6; r = 0.91, p<0.001). In the n-3 group significantly higher increase was found in n-3 PUFA (eicosapentaenoic acid, 20:5n-3, docosahexaenoic acid, 22:6n-3) in triglycerides and phospholipids. The significant decrease of palmitoleic acid (16:1n-7) and vaccenic acid (18:1n-7) in triglycerides probably reflected lower lipogenesis. A significant negative correlation between BMI change and phospholipid docosahexaenoic acid change was found (r = -0.595, p<0.008). The results suggest that long chain n-3 PUFA enhance weight loss in obese females treated by VLCD. Docosahexaenoate (22:6n-3) seems to be the active component.     

Alteration of plasma phospholipid fatty acid profile in patients with septic shock

In septic shock patients, alterations of plasma phospholipid fatty acid profile have never been described. The purpose of this monocentric, non-interventional, observational prospective study was to describe this fatty acid profile in the early phase of septic shock in intensive care unit. Thirty-seven adult patients with septic shock were included after the first day of stay in intensive care unit, before any form of artificial nutritional support. Plasma phospholipid fatty acid composition was determined by gas chromatography. All biological data from patients with septic shock were compared with laboratory reference values. Patients presented hypocholesterolemia and hypertriglyceridemia. They had low concentrations of phospholipid fatty acids specifically n-6 and n-3 polyunsaturated fatty acids (PUFAs) with a high n-6/n-3 ratio. Plasma phospholipid PUFA concentrations were strongly correlated with cholesterolemia. PUFAs/SFAs (saturated fatty acids) and PUFAs/MUFAs (monounsaturated fatty acids) ratios were low because of low percentage of n-6 and n-3 PUFAs and high percentage of SFAs and MUFAs. Low levels of plasma long chain PUFAs (≥20 carbons) were significantly associated with mortality at 28th day. In conclusion, plasma phospholipid FA profile of septic patients is very characteristic, close to that of acute respiratory distress syndrome and mortality is associated with long chain PUFA decrease. This profile could be explained by numerous non-exclusive physio-pathological processes 1) an activation of hepatic de novo lipogenesis that could contribute to hepatic steatosis, 2) an elevated adipose tissue lipolysis, 3) an increased free radical attack of FA by oxidative stress, 4) an over-production of inflammatory lipid mediators.