Compartmental analysis of plasma and liver n-3 essential fatty acids in alcohol-dependent men during withdrawal

The mechanism by which chronic ethanol consumption reduces concentrations of long chain polyunsaturated (LCP) fatty acids (FA) in tissues of humans was investigated in alcohol-dependent (AD) men during early withdrawal and to a well-matched control group by fitting the concentration-time curves of d(5)-labeled n-3 FA from plasma and liver, which originated from an oral dose of d(5)-linolenic acid (d(5)-18:3n-3) ethyl ester to a compartmental model. Blood sampled over 168 h and a liver specimen obtained 96 h after isotope administration were analyzed for d(5)-18:3n-3, d(5)-20:5n-3, d(5)-22:5n-3, and d(5)-22:6n-3. Plasma 20:5n-3 and 22:5n-3 were lower in AD subjects, compared with controls (20:5n-3: -50%, 22:5n-3: -34%). Increased amounts of d(5)-18:3n-3 were directed toward synthesis of d(5)-20:5n-3 in AD subjects (P < .05). However, this effect was offset by larger amounts of 20:5n-3 lost from plasma (control: 2.0 vs. AD: 4.2 mg d(-1)). In livers of AD subjects, more d(5)-18:3n-3 and d(5)-22:5n-3 were utilized for synthesis of d(5)-20:5n-3 (+200%) and d(5)-22:6n-3 (+210%), respectively, than was predicted from plasma kinetics. Although, the potential to utilize linolenic acid for synthesis of LCP FA was greater in AD subjects compared with controls, heightened disappearance rates of 20:5n-3 reduced overall plasma concentrations of several endogenous n-3 LCP FA.     

Physiological compartmental analysis of alpha-linolenic acid metabolism in adult humans

A physiological compartmental model of alpha-linolenic acid metabolism was derived from the plasma concentration-time curves for d5-18:3n-3, d5-20:5n-3, d5-22:5n-3, and d5-22:6n-3 in eight healthy subjects. Subjects received a 1-g oral dose of an isotope tracer of alpha-linolenate (d5-18:3n-3 ethyl ester) while subsisting on a rigorously controlled beef-based diet. By utilizing the Windows Simulation and Analysis Modeling program, kinetic parameters were determined for each subject. Half-lives and mean transit times of the n-3 fatty acids in the plasma were also determined. The model predicted plasma values for the n-3 fatty acids in good accordance with the measured steady state concentrations and also predicted dietary linolenic acid intake for each subject in accordance with values determined by lipid analysis of the diet. Only about 0.2% of the plasma 18:3n-3 was destined for synthesis of 20:5n-3, approximately 63% of the plasma 20:5n-3 was accessible for production of 22:5n-3, and 37% of 22:5n-3 was available for synthesis of 22:6n-3. The inefficiency of the conversion of 18:3n-3 to 20:5n-3 indicates that the biosynthesis of long-chain n-3 PUFA from alpha-linolenic acid is limited in healthy individuals. In contrast, the much greater rate of transfer of mass from the plasma 20:5n-3 compartment to 22:5n-3 suggests that dietary eicosapentaenoic acid may be well utilized in the biosynthesis of 22:6n-3 in humans.     

Effects of olive and fish oil Ca soaps in ewe diets on milk fat and muscle and subcutaneous tissue fatty-acid profiles of suckling lambs

Enhancing healthy fatty acids (FAs) in ewe milk fat and suckling lamb tissues is an important objective in terms of improving the nutritional value of these foods for the consumer. The present study examined the effects of feeding-protected lipid supplements rich in unsaturated FAs on the lipid composition of ewe milk, and subsequently in the muscle and subcutaneous adipose tissues of lambs suckling such milk. Thirty-six pregnant Churra ewes with their new-born lambs were assigned to one of three experimental diets (forage/concentrate ratio 50 : 50), each supplemented with either 3% Ca soap FAs of palm (Control), olive (OLI) or fish (FO) oil. The lambs were nourished exclusively by suckling for the whole experimental period. When the lambs reached 11 kg BW, they were slaughtered and samples were taken from the Longissimus dorsi and subcutaneous fat depots. Although milk production was not affected by lipid supplementation, the FO diet decreased fat content (P<0.001), whereas the OLI milk FA profile resembled that of the Control diet. In contrast, although FO drastically diminished the contents of stearic and oleic acids (P<0.001), all the saturated even-numbered carbon FAs from 6:0 to 14:0 increased (P<0.05). FO also produced the highest levels of c9,t11-18:2 (2.21%) and n-3 FAs, 20:5 n-3 (0.58%), 22:5 n-3 (0.48%) and 22:6 n-3 (0.40%). The high levels of trans-11 18:1 (7.10%) obtained from the FO diet would suggest that Ca soaps only confer partial protection in the rumen. In contrast, the lack of significant differences in trans-10 18:1 levels (P>0.05) and other trans-FAs between Control and FO treatments would indicate that FO treatment does not alter rumen biohydrogenation pathways under the assayed conditions. Changes in dam milk FA composition induced differences in the FA profiles of meat and fat depots of lambs, preferentially incorporated polyunsaturated FAs into the muscle rather than storing them in the adipose tissue. In the intramuscular fat of the FO treatment, all the n-3 FAs reached their highest concentrations: 0.97 (18:3 n-3), 2.72 (20:5 n-3), 2.21 (22:5 n-3) and 1.53% (22:6 n-3). In addition, not only did FO intramuscular fat have the most cis-9, trans-11 18:2 (1.66%) and trans-11 18:1 (3.75%), but also the lowest n-6/n-3 ratio (1.80) and saturated FA content were not affected. Therefore, FO exhibited the best FA profile from a nutritional point of view.     

Effects of Nucleotides Supplementation of Infant Formulas on Plasma and Erythrocyte Fatty Acid Composition: A Meta-Analysis

Objective

Nucleotides (NTs) have been added to infant formulas for several years due to their health benefits. However, studies have reported inconsistent findings regarding the association between NTs and fatty acid (FA) composition. A meta-analysis was performed to assess the effects of NTs supplementation of infant formula on erythrocyte and plasma FA composition.

Methods

Randomized controlled trials that evaluated the association between NTs supplementation and FA composition and were published before October 2014 were included. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. Heterogeneity was assessed using Q and I ² tests.

Results

Eight studies (364 infants) were included in the meta-analysis. NTs supplementation did not affect the concentrations of total saturated FAs (SMD= 0.05; 95% CI= -0.23–0.32; P = 0.75) or total monounsaturated FAs (SMD= -0.01; 95% CI= -0.28–0.27; P = 0.95) in erythrocyte membranes. Erythrocyte total n-3 (SMD= 0.15; 95% CI= -0.11–0.41; P = 0.27) and n-6 PUFA (SMD= -0.16; 95% CI= -0.42–0.10, P = 0.22) concentrations did not increase with NTs supplementation. The concentrations of erythrocyte n-3 PUFA (18:3, 20:5, 22:5, and 22:6) and n-6 PUFA (18:2, 20:3, 20:4, and 22:4) were not affected by NTs supplementation. NTs significantly increased plasma concentrations of 18:2 n-6 (SMD= 0.90; 95% CI= 0.47–1.33; P < 0.0001), 20:3 n-6 (SMD= 0.56; 95% CI= 0.14–0.97; P = 0.009), and 20:4 n-6 PUFA (SMD= 0.92; 95% CI= 0.50–1.35; P < 0.0001), and significantly decreased the concentration of plasma 18:3 n-3 PUFA (SMD= -0.60; 95% CI -1.12 to -0.09; P = 0.02). No effect was obtained on plasma 20:2 n-6 PUFA concentrations (SMD= 0.06; 95 % CI, -1.03 to -0.2; P = 0.93).

Conclusions

Our meta-analysis revealed that NTs supplementation significantly increased plasma 18:2 n-6, 20:3 n-6, and 20:4 n-6 PUFA concentrations in infants, but did not affect erythrocyte FA composition.     

Biosynthesis of polyunsaturated fatty acids in zooxanthellae and polyps of corals

The fatty acid (FA) composition of zooxanthellae, polyp tissue, and intact colonies was determined in soft coral Sinularia sp. and hard coral Acropora sp. Analysis of the distribution of polyunsaturated fatty acids (PUFAs) among the zooxanthellae and the host organism showed that 18: 3n-6 and C_18–22 PUFAs of the n-3 series (18: 4n-3, 20: 5n-3, 22: 5n-3, and 22: 6n-3) were mainly synthesized by the zooxanthellae and that C_20–22 PUFAs of the n-6 series (20: 3n-6, 20: 4n-6, and 22: 4n-6) were synthesized in the polyp tissue. Soft coral polyps were able to synthesize tetracosapolyenoic FAs (24: 5n-6 and 24: 6n-3) and 18: 2n-7, their zooxanthellae synthesized C₁₆ PUFAs (16: 2n-7, 16: 3n-4, and 16: 4n-1). It is supposed that the biosynthesis of 16: 2n-7 in Sinularia sp. and 18: 3n-6 in Acropora sp. is catalyzed by Δ6 desaturase. The relatively even distribution of three FAs (18: 2n-6, 18: 3n-6, and 16: 2n-7) among lipids of zooxanthellae and coral polyps indicates the possible transport of these FAs between symbionts and the host organism.     

In vivo conversion of 18- and 20-C essential fatty acids in rats using the multiple simultaneous stable isotope method

An important question for mammalian nutrition is the relative efficiency of C18 versus C20 essential fatty acids (EFAs) for supporting the tissue composition of n-3 and n-6 pathway end products. One specific question is whether C22 EFAs are made available to tissues more effectively by dietary alpha-linolenic acid (18:3n-3) and linoleic acid (18:2n-6) or by dietary eicosapentaenoic acid (20:5n-3) and dihomo-gamma-linolenic acid (20:3n-6). To address this question in a direct manner, four stable isotope compounds were given simultaneously in a novel paradigm. A single oral dose of a mixture of 2H5-18:3n-3, 13C-U-20:5n-3, 13C-U-18:2n-6, and 2H5-20:3n-6 was administered to rats given a defined diet. There was a preferential in vivo conversion of arachidonic acid (20:4n-6) to docosatetraenoic acid (22:4n-6) and of 22:4n-6 to n-6 docosapentaenoic acid (22:5n-6) when the substrates originated from the C18 precursors. However, when the end products docosahexaenoic acid (22:6n-3) or 22:5n-6 were expressed as the total amount in the plasma compartment divided by the dosage, this parameter was 11-fold greater for 20:5n-3 than for 18:3n-3 and 14-fold greater for 20:3n-6 than for 18:2n-6. Thus, on a per dosage basis, the total amounts of n-3 and n-6 end products accreted in plasma were considerably greater for C20 EFA precursors relative to C18.     

Vitamin E kinetics in smokers and nonsmokers.

Does cigarette smoking increase vitamin E utilization in vivo? A trial was carried out in 6 smokers and 5 nonsmokers of comparable ages and serum lipids. Subjects consumed 75 mg each d(3)-RRR and d(6)-all rac-alpha-tocopheryl acetates (natural and synthetic vitamin E, respectively) daily for 7 d with a standardized breakfast. Fasting blood samples were drawn on days -7, -6, -5, -4, -3, -2, -1, 0, 1, 2, 3, 4, 5, 6, 7, 9, 14, 21 (negative days indicate supplementation). In both groups, plasma d(3)-alpha-tocopherol concentrations were approximately double of d(6)-alpha-tocopherol. At day 0, the %d(3) alpha-tocopherols (d(3)-alpha-tocopherol/total-alpha-tocopherol x 100) were similar in both smokers and nonsmokers. Subsequently, there was a trend toward a faster exponential disappearance of the plasma %d(3) alpha-tocopherol in smokers compared with nonsmokers (0.30 +/- 0.04 compared with 0.24 +/- 0.05, p =.0565). The calculated %d(3) half-lives were 55.6 +/- 7.4 h in smokers and 72.1 +/- 17.3 h in nonsmokers (p =.0630). By day 21, the %d(3) in smokers had decreased to 1.4% +/- 0.3% while it was 2.2% +/- 0.7% (p =.0418) in the nonsmokers. These data suggest that smoking increases plasma vitamin E disappearance, but further studies are needed to confirm this finding and to assess its cause.     

Fatty acids in common minke whale (Balaenoptera acutorostrata) blubber reflect the feeding area and food selection,but also high endogenous metabolism

The fatty acid (FA) composition has been analysed in the blubber of 56 minke whales caught during the Norwegian commercial whaling period in 2009–2011. Minke whales from four regions were sampled: the North Sea, Vesterålen, Spitsbergen/Bear Island and Finnmark. The FA profiles of the whale blubber have been compared with FA profiles of potential prey species to investigate if FA analysis can be used to predict the diet of minke whales and how the FA profiles of the blubber reflect the regional ecosystem in which the whales were caught. Clear differences in blubber FA profiles were found between minke whales from different areas, and the results of the present study show that FA analysis of the blubber can be used to indicate the whale's diet, but there appears to be a strong impact from metabolism on several FAs. The whale blubber FAs are separate from those of the prey by having relatively high levels of FAs likely to originate from endogenous metabolism, such as 18:1n9 (Δ9-desaturation of 18:0); chain shortening products of 22:1(n-11); 20:1(n-11) and 18:1(n-11); as well as 22:5(n-3), which is an elongation product of 20:5(n-3). High metabolic activity in the adipose tissue was also evident by the clear stratification of FA profiles found throughout the blubber layer. It is remarkable that the whale blubber has much lower levels of the long-chain PUFAs 20:5(n-3) and 22:6(n-3) than found in the prey organisms. It is likely that this results from selective partitioning of diet FAs between the storage lipids and membrane lipids.     

Comparison of fatty acid compositions of azooxanthellate Dendronephthya and zooxanthellate soft coral species

Ten zooxanthellae-free Dendronephthya species , twelve zooxanthellate soft coral species of the genera Sarcophyton, Lobophytum, Cladiella, Lytophyton, Cespitularia, and Clavularia, and the hermatypic coral Caulastrea tumida were examined for the first time to elucidate the fatty acid (FA) composition of total lipids. In Dendronephthya species, the main FAs were 20:4n-6, 24:5n-6, 16:0, 18:0, 7-Me-16:1n-10, and 24:6n-3 which amounted on the average to 26.0, 12.7, 12.1, 6.0, 4.8, and 4.0% of the total FA contents, respectively. For zooxanthellate soft corals, the main FAs were 16:0 (25.7%), 20:4n-6 (18.2%), 24:5n-6 (6.2%), and 18:4n-3 (5.6%), as well as 16:2n-7, which amounted up to 11.8% in Sarcophyton aff. crassum. Corals with zooxanthellae had low contents of 24:6n-3. The significant difference (p<0.01) between azooxanthellate and zooxanthellate soft corals was indicated only for 12 of 46 FAs determined. The principal components analysis confirmed that 7-Me-16:1n-10, 17:0, 18:4n-3, 18:1n-7, 20:4n-6, 22:5n-6, 24:5n-6, and 24:6n-3 are useful for chemotaxonomy of Dendronephthya. The azooxanthellate soft corals studied were distinguished by the absence of significant depth-dependent and species-specific variations of FA composition, low content of 16:2n-7, an increased proportion of bacterial FAs, predominance of n-6 FAs connected with active preying, and a high ability for biosynthesis of tetracosapolyenoic FAs.     

Developmental changes in rat brain membrane lipids and fatty acids. The preferential prenatal accumulation of docosahexaenoic acid

Information on the prenatal accumulation of rat brain membrane lipids is scarce. In this study we investigated in detail the fatty acid (FA) composition of the rat brain, on each day from embryonic day 12 (E12) up to birth, and on 8 time points during the first 16 days of postnatal life, and correlated the FA changes with well-described events of neurogenesis and synaptogenesis. Between E14 and E17, there was a steep increase in the concentration of all the FAs: 16:0 increased by 136%, 18:0 by 139%, 18:1 by 92%, 20:4n-6 by 98%, 22:4n-6 by 116%, 22:5n-6 by 220%, and 22:6n-3 by 98%. After this period and up to birth, the concentration of the FAs plateaued, except that of 22:6n-3, which accumulated further, reaching an additional increase of 75%. After birth, except 22:5n-6, all FAs steadily increased at various rates. Estimation of the FA/PL molar ratios showed that prenatally the ratios of all the FAs either decreased or remained constant, but that of 22:6n-3 increased more than 2-fold; postnatally the ratios remained constant, with the exception of 22:4n-6 and 22:5n-6, which decreased. In conclusion, prenatal accumulation of brain fatty acids parallels important events in neurogenesis. 22:6n-3 is exceptional inasmuch in its steep accumulation occurs just prior to synaptogenesis.     

The Composition of fatty acids and aldehydes of the marine bryozoans <Emphasis Type="Italic">Berenicea meandrina</Emphasis> and <Emphasis Type="Italic">Dendrobeania flustroides</Emphasis> (Bryozoa: Gymnolaemata)

This study examines the composition of lipids, fatty acids, and fatty aldehydes in two marine bryozoan species, Berenicea meandrina and Dendrobeania flustroides, from the Sea of Okhotsk. The share of neutral lipids was up to 57.3% in D. flustroides and 54.9% in B. meandrina; the share of polar lipids was 33.2 and 40.4%, respectively. In all, 57 fatty acids (FA) and 9 aldehydes were identified in total lipids. The main FAs were 16:0, 18:0, 22:6n-3, and 20:5n-3. The content of branched saturated FA in bryozoans was on the average 6.4%. Three isomers of 16:1 (n-9, n-7, and n-5), five isomers of 18:1 (n-13, n-11, n-9, n-7, and n-5), four isomers of 20:1 (n-13, n-11, n-9, and n-7), as well as 22:1n-9 and 22:1n-13 were found; the presence of 7-methyl-6-hexadienoic acid (on the average, 3.0% of total FAs) was demonstrated. Non-methylene-inter-rupted FAs contributed 8.9 and 1.6% of the total FAs in D. flustroides and B. meandrina, respectively, and were identified as 20:2(5,11), 20:2(7,13), 20:3(5,11,14), 22:2(7,13), and 22:2(7,15). In B. meandrina, minor amounts of 24:0, 24:1, 25:0, 26:0, 24:4n-3, 26:3(5,9,19), and 28:3(5,9,19) were found, suggesting sponge biofouling on some bryozoan colonies. Aldehydes (branched saturated and unsaturated C_16–19 homologues) did not exceed 10.3 and 1.9% of the total FAs in D. flustroides and B. meandrina, respectively. The presence of the FA markers that are characteristic of microalgae, protozoans, and detritus in bryozoan lipids agrees well with data on polytrophic feeding of these bryozoans.     

The role of free fatty acids in mitochondrial energetic metabolism in winter wheat seedlings

The effect of fatty acids (FAs) (C12–C24) on the functioning of winter wheat (Triticum aestivum L.) mitochondria was studied. Such fatty acids as C12:0, C16:0, and C18:0 and unsaturated FAs, such as C18:1 (n-9 cis), C18:1 (n-12 cis), C18:2 (n-9, 12), (18:3, n-3), and C22:1 (n-9 cis) caused efficient uncoupling of oxidative phosphorylation in mitochondria, i.e., an increase in the nonphosphorylating respiration rate and a decrease in the respiratory control value. It was established that C16:0 had the strongest uncoupling effect among all saturated FAs, and C18:3, among unsaturated FAs. The uncoupling effect of saturated FAs is provided by the ADP/ATP-antiporter, while plant uncoupling proteins play an important role in the uncoupling effect of unsaturated FAs. In addition, unsaturated, as well as saturated FAs might serve as oxidative substrates for mitochondria. It was concluded that the role of FAs in energetic metabolism of winter wheat seedlings consisted of uncoupling of oxidative phosphorylation and of serving as substrates for oxidation.     

Maternal grazing on stubble and Mediterranean shrubland improves meat lipid profile in light lambs fed on concentrates

Concentrates-fed lamb meat is often associated with an unfavourable lipid profile (high levels of saturated and/or n-6 polyunsaturated fatty acids; SFA and PUFA). For this reason, Spanish sheep producers from Mediterranean areas are turning to traditional grazing by ewes to obtain healthier lamb meat. The objective of this research was to determine the effects of maternal grazing on the fatty acid (FA) composition of weaned lamb meat. The ewes (Segureña breed) were allocated to two different rearing systems during pregnancy (5 months) and lactation (45 days): (i) feeding indoors on barley grain and lucerne pellets; (ii) grazing on cereal stubble, fallow land and seasonal pastures consisting of Mediterranean shrubs, herbs and trees. Two groups of 20 autumn and spring lambs were sampled. The lambs were weaned at 13.1±0.9 kg and 45.0±4.1 days age and fed on grain-based concentrates until they reached 24.8±2.1 kg live weight (light lambs slaughtered at 98.3±3.6 days of age). The FA content was determined in the intramuscular loin fat by gas chromatography using a flame ionization detector. The ewe diet did not affect the levels of the main lamb FAs (C18:1c+t, C16:0 and C18:2c), and so did not provide any additional reduction in fat saturation. Saturated fatty acids represented around 40% of total FAs determined in the meat. Ewe grazing acted as an n-3 PUFA-promoting diet, providing a lamb meat with a lower n-6/n-3 ratio. Spring lamb meat had higher proportions of n-3 PUFA (C18:3n-3, C20:5, C22:5 and C22:6) and conjugated linoleic acid (C18:2c9t11+c11t9) to the detriment of the n-6 PUFAs (C20:4, C20:2 and C22:4), while autumn lamb meat also had higher levels of C18:3n-3 and C18:3n-6, and lower level of C20:4, which points to little seasonal differences. The n-6/n-3 ratio achieved by ewe grazing fell from 8.2 to 4.1 (Spring) and from 7.6 to 5.5 (Autumn), values which are close to those recommended in human diet for good cardiovascular health. These n-6/n-3 reductions were associated with lower levels of total PUFA and C20:4n-6. Our research concluded that grazing on stubble and Mediterranean shrubland by ewes, a sustainable rearing practice involving local agro resources, contributed to obtaining weaned lamb meat with a more favourable lipid profile and so can be recommended to sheep farmers.     

Determination of membrane cholesterol partition coefficient using a lipid vesicle-cyclodextrin binary system: effect of phospholipid acyl chain unsaturation and headgroup composition

Lateral domain or raft formation in biological membranes is often discussed in terms of cholesterol-lipid interactions. Preferential interactions of cholesterol with lipids, varying in headgroup and acyl chain unsaturation, were studied by measuring the partition coefficient for cholesterol in unilamellar vesicles. A novel vesicle-cyclodextrin system was used, which precludes the possibility of cross-contamination between donor-acceptor vesicles or the need to modify one of the vesicle populations. Variation in phospholipid headgroup resulted in cholesterol partitioning in the order of sphingomyelin (SM) > phosphatidylserine > phosphatidylcholine (PC) > phosphatidylenthanolamine (PE), spanning a range of partition DeltaG of -1181 cal/mol to +683 cal/mol for SM and PE, respectively. Among the acyl chains examined, the order of cholesterol partitioning was 18:0(stearic acid),18:1n-9(oleic acid) PC > di18:1n-9PC > di18:1n-12(petroselenic acid) PC > di18:2n-6(linoleic acid) PC > 16:0(palmitic acid),22:6n-3(DHA) PC > di18:3n-3(alpha-linolenic acid) PC > di22:6n-3PC with a range in partition DeltaG of 913 cal/mol. Our results suggest that the large differences observed in cholesterol-lipid interactions contribute to the forces responsible for lateral domain formation in plasma membranes. These differences may also be responsible for the heterogeneous cholesterol distribution in cellular membranes, where cholesterol is highly enriched in plasma membranes and relatively depleted in intracellular membranes.     

Combined (n-3 and n-6) essential fatty deficiency is a potent modulator of plasma lipids, lipoprotein composition, and lipolytic enzymes

Essential fatty acids (EFA) are important structural and functional components of cell membranes. Their deficiency has been associated with several clinical and biochemical abnormalities. In the present study, the lipid profile as well as the concentration, composition, and metabolism of lipoproteins were examined in rats rendered EFA-deficient over a period of 12 weeks. Changes in plasma fatty acids mainly induced an increase of palmitoleic (16:1 n-7) and eicosatrienoic (20:3 n-9) acids, while linoleic (18:2 n-6), arachidonic (20:4 n-6), linolenic (18:3 n-3), and docosahexaenoic (22:6 n-3) acids were decreased. The results show increased concentrations of free fatty acids (FFA) (P less than 0.001), triglycerides (P less than 0.001), total cholesterol (P less than 0.02), free cholesterol (P less than 0.005), and phospholipids (P less than 0.05) when compared to pair-fed controls. Similar levels of cholesteryl esters were found in the two groups, and lecithin: cholesterol acyltransferase activity (nmol/100 microliters plasma per h) (8.98 +/- 1.44 vs 8.72 +/- 0.50) did not differ. On the other hand, postheparin extrahepatic lipoprotein lipase (LPL) activity was significantly (P less than 0.002) decreased (5.96 +/- 0.29 vs 7.29 +/- 0.68 mumol FFA/ml per h) and could account for the hypertriglyceridemia as well for the relative triglyceride enrichment of very low density lipoprotein, intermediate density lipoprotein, and low density lipoprotein particles. This enzymatic depletion of LPL was mainly due to the adipose tissue, since a higher level (P less than 0.001) of hepatic lipase (325.8 +/- 16.0 vs 130.8 +/- 9.5 nmol FFA/mg protein per h) was found in liver acetone powder extracts.(ABSTRACT TRUNCATED AT 250 WORDS)     

Simultaneous quantitative determination of deuterium- and carbon-13-labeled essential fatty acids in rat plasma

This study reports methods for the quantitative determination of stable isotope-labeled essential fatty acids (EFAs) as well as an experiment in which deuterium-labeled linoleic acid (18:2n-6) and alpha-linolenic acid (18:3n-3) were compared with those labeled with carbon-13 in rat plasma in vivo. Standard curves were constructed to compensate for concentration and plasma matrix effects. It was observed that endogenous pools of fatty acids had a greater suppressing effect on the measurements of 13C-U-labeled EFAs relative to those labeled with 2H5. Using these methods, the in vivo metabolism of orally administered deuterated-linolenate, 13C-U-labeled linolenate, deuterated-linoleate, and 13C-U-labeled linoleate was compared in adult rats (n = 11). There were no significant differences in the concentrations of the 2H versus 13C isotopomers of 18:2n-6, 18:3n-3, arachidonic acid (20:4n-6), and docosahexaenoic acid (22:6n-3) in rat plasma samples at 24 h after dosing. Thus, there appears to be little isotope effect for 2H5- versus 13C-U-labeled EFAs when the data are calculated using the conventional standard curves and corrected for endogenous fatty acid pool size and matrix effects.     

Fatty acid composition of membrane bilayers: Importance of diet polyunsaturated fat balance

In one of the most extensive analyses to date we show that the balance of diet n-3 and n-6 polyunsaturated fatty acids (PUFA) is the most important determinant of membrane composition in the rat under 'normal' conditions. Young adult male Sprague-Dawley rats were fed one of twelve moderate-fat diets (25% of total energy) for 8weeks. Diets differed only in fatty acid (FA) profiles, with saturate (SFA) content ranging 8-88% of total FAs, monounsaturate (MUFA) 6-65%, total PUFA 4-81%, n-6 PUFA 3-70% and n-3 PUFA 1-70%. Diet PUFA included only essential FAs 18:2n-6 and 18:3n-3. Balance between n-3 and n-6 PUFA is defined as the PUFA balance (n-3 PUFA as % of total PUFA) and ranged 1-86% in the diets. FA composition was measured for brain, heart, liver, skeletal muscle, erythrocytes and plasma phospholipids, as well as adipose tissue and plasma triglycerides. The conformer-regulator model was used (slope=1 indicates membrane composition completely conforming to diet). Extensive changes in diet SFA, MUFA and PUFA had minimal effect on membranes (average slopes 0.01, 0.07, 0.07 respectively), but considerable influence on adipose tissue and plasma triglycerides (average slopes 0.27, 0.53, 0.47 respectively). Diet balance between n-3 and n-6 PUFA had a biphasic influence on membrane composition. When n-3 PUFA<10% of total PUFA, membrane composition completely conformed to diet (average slope 0.95), while diet PUFA balance>10% had little influence (average slope 0.19). The modern human diet has an average PUFA balance ~10% and this will likely have significant health implications.     

Whole body distribution of deuterated linoleic and alpha-linolenic acids and their metabolites in the rat

Little is known about the uptake or metabolism of essential fatty acids (EFAs) in various mammalian organs. Thus, the distribution of deuterated alpha-linolenic acid (18:3n-3) and linoleic acid (18:2n-6) and their metabolites was studied using a stable isotope tracer technique. Rats were orally administered a single dose of a mixture (20 mg each) of ethyl D5-18:3n-3 and D5-18:2n-6, and 25 tissues per animal were analyzed for D5-labeled PUFAs at 4, 8, 24, 96, 168, 240, 360, and 600 h after dosing. Plasma, stomach, and spleen contained the highest concentrations of labeled precursors at the earliest time points, whereas other internal organs and red blood cells reached their maximal concentrations at 8 h. The time-course data were consistent with liver metabolism of EFAs, but local metabolism in other tissues could not be ruled out. Brain, spinal cord, heart, testis, and eye accumulated docosahexaenoic acid with time, whereas skin accumulated mainly 20:4n-6. On average, approximately 16-18% of the D5-18:3n-3 and D5-18:2n-6 initial dosage was eventually accumulated in tissues, principally in adipose, skin, and muscle. Approximately 6.0% of D5-18:3n-3 and 2.6% of D5-18:2n-6 were elongated/desaturated and stored, mainly in muscle, adipose, and the carcass. The remaining 78% of both precursors was apparently catabolized or excreted.