Adipose tissue fatty acid patterns and changes in anthropometry: a cohort study

Introduction

Diets rich in n-3 long chain polyunsaturated fatty acids (LC-PUFA), but low in n-6 LC-PUFA and 18:1 trans-fatty acids (TFA), may lower the risk of overweight and obesity. These fatty acids have often been investigated individually. We explored associations between global patterns in adipose tissue fatty acids and changes in anthropometry.

Methods

34 fatty acid species from adipose tissue biopsies were determined in a random sample of 1100 men and women from a Danish cohort study. We used sex-specific principal component analysis and multiple linear regression to investigate the associations of adipose tissue fatty acid patterns with changes in weight, waist circumference (WC), and WC controlled for changes in body mass index (WC_BMI), adjusting for confounders.

Results

7 principal components were extracted for each sex, explaining 77.6% and 78.3% of fatty acid variation in men and women, respectively. Fatty acid patterns with high levels of TFA tended to be positively associated with changes in weight and WC for both sexes. Patterns with high levels of n-6 LC-PUFA tended to be negatively associated with changes in weight and WC in men, and positively associated in women. Associations with patterns with high levels of n-3 LC-PUFA were dependent on the context of the rest of the fatty acid pattern.

Conclusions

Adipose tissue fatty acid patterns with high levels of TFA may be linked to weight gain, but patterns with high n-3 LC-PUFA did not appear to be linked to weight loss. Associations depended on characteristics of the rest of the pattern.     

Dietary LC-PUFA and environmental salinity modulate the fatty acid biosynthesis capacity of the euryhaline teleost thicklip grey mullet (Chelon labrosus)

The capacity to biosynthesise long-chain (≥C20) polyunsaturated fatty acids (LC-PUFA) depends upon the complement and function of key enzymes commonly known as fatty acyl desaturases and elongases. The presence of a Δ5/Δ6 desaturase enabling the biosynthesis of docosahexaenoic acid (22:6n-3, DHA) through the “Sprecher pathway” has been reported in Chelon labrosus. Research in other teleosts have demonstrated that LC-PUFA biosynthesis can be modulated by diet and ambient salinity. The present study aimed to assess the combined effects of partial dietary replacement of fish oil (FO) by vegetable oil (VO) and reduced ambient salinity (35 ppt vs 20 ppt) on the fatty acid composition of muscle, enterocytes and hepatocytes of C. labrosus juveniles. Moreover, the enzymatic activity over radiolabelled [1-¹⁴C] 18:3n-3 (α-linolenic acid, ALA) and [1-¹⁴C] 20:5n-3 (eicosapentaenoic acid, EPA) to biosynthesise n-3 LC-PUFA in hepatocytes and enterocytes, and the gene regulation of the C. labrosus fatty acid desaturase-2 (fads2) and elongation of very long chain fatty acids protein 5 (elovl5) in liver and intestine was also investigated. Recovery of radiolabelled products including stearidonic acid (18:4n-3, SDA), 20:5n-3, tetracosahexaenoic acid (24:6n-3, THA) and 22:6n-3 in all treatments except FO35-fish, provided compelling evidence that a complete pathway enabling the biosynthesis of EPA and DHA from ALA is present and active in C. labrosus. Low salinity conditions upregulated fads2 in hepatocytes and elovl5 in both cell types, regardless of dietary composition. Interestingly, FO20-fish showed the highest amount of n-3 LC-PUFA in muscle, while no differences in VO-fish reared at both salinities were found. These results demonstrate a compensatory capacity of C. labrosus to biosynthesise n-3 LC-PUFA under reduced dietary supply, and emphasise the potential of low salinity conditions to stimulate this pathway in euryhaline fish.     

Effects of dietary incorporation of linseed oil with soybean isoflavone on fatty acid profiles and lipid metabolism-related gene expression in breast muscle of chickens

The meat quality of chicken is an important factor affecting the consumer’s health. It was hypothesized that n-3 polyunsaturated fatty acid (n-3 PUFA) could be effectively deposited in chicken, by incorporating antioxidation of soybean isoflavone (SI), which led to improved quality of chicken meat for good health of human beings. Effects of partial or complete dietary substitution of lard (LA) with linseed oil (LO), with or without SI on growth performance, biochemical indicators, meat quality, fatty acid profiles, lipid-related health indicators and gene expression of breast muscle were examined in chickens. A total of 900 males were fed a corn–soybean meal diet supplemented with 4% LA, 2% LA + 2% LO and 4% LO and the latter two including 30 mg SI/kg (2% LA + 2% LO + SI and 4% LO + SI) from 29 to 66 days of age; each of the five dietary treatments included six replicates of 30 birds. Compared with the 4% LA diet, dietary 4% LO significantly increased the feed efficiency and had no negative effect on objective indices related to meat quality; LO significantly decreased plasma triglycerides and total cholesterol (TCH); abdominal fat percentage was significantly decreased in birds fed the 4% LO and 4% LO + SI diets. Chickens with LO diets resulted in higher contents of α-linolenic acid (C18:3n-3), EPA (C20:5n-3) and total n-3 PUFA, together with a lower content of palmitic acid (C16:0), lignoceric acid (C24:0), saturated fatty acids and n-6:n-3 ratio in breast muscle compared to 4% LA diet (P < 0.05); they also significantly decreased atherogenic index, thrombogenic index and increased the hypocholesterolemic to hypercholesterolemic ratio. Adding SI to the LO diets enhanced the contents of EPA and DHA (C22:6n-3), plasma total superoxide dismutase, reduced glutathione (GSH)/oxidized glutathione and muscle GSH content, while decreased plasma total triglyceride and TCH and malondialdehyde content in plasma and breast muscle compared to its absence (P < 0.05). Expression in breast muscle of fatty acid desaturase 1 (FADS1), FADS2, elongase 2 (ELOVL2) and ELOVL5 genes were significantly higher with the LO diets including SI than with the 4% LA diet. Significant interactions existed between LO level and inclusion of SI on EPA and TCH contents. These findings indicate that diet supplemented with LO combined with SI is an effective alternative when optimizing the nutritional value of chicken meat for human consumers.     

Fatty acid composition of liver, adipose tissue, spleen, and heart of mice fed diets containing t10, c12-, and c9, t11-conjugated linoleic acid

Conjugated linoleic acid (CLA) isomers have unique effects on tissue lipids. Here we investigated the influence of individual CLA isomers on the lipid weight and fatty acid composition of lipid metabolizing (i.e. liver and retroperitoneal adipose) and lipid sensitive (i.e. spleen and heart) tissues. Female mice (8 week old; n=6/group) were fed either a control or one of the two CLA isomer supplemented (0.5%) diets for 8 weeks. The cis-9, trans-11-CLA diet reduced the 18:1n-9 wt% by 20-50% in liver, adipose tissue, and spleen, reduced the spleen n-3 polyunsaturated fatty acid (PUFA) by 90%, and increased the n-6 PUFA wt% by 20-50% in all tissues except heart. The trans-10, cis-12-CLA reduced both the n-6 and n-3 PUFA wt% in liver (>50%), reduced the heart n-3 PUFA wt% by 25%, and increased the wt% of spleen n-3 PUFA by 700%. The functional consequences of such changes in tissue fatty acid composition need to be investigated.     

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.     

Estrogen and n-3 polyunsaturated fatty acid supplementation have a synergistic hypotriglyceridemic effect in ovariectomized rats

The n-3 polyunsaturated fatty acids (PUFAs), EPA and DHA, as well as estrogen have been shown to decrease circulating levels of triglyceride (TG), but their underlying mode of action is unclear. The purpose of this study was to determine the effects of n-3 PUFA consumption and estrogen injection on TG metabolism. Rats (n = 48) were fed a modified AIN-93G diet with 0, 1, or 2 % EPA + DHA relative to the total energy intake during 12 weeks. At 8 weeks, rats were ovariectomized (OVX), and after a 1-week recovery, rats were injected with either 17β-estradiol-3-benzoate (E₂) or corn oil for the last 3 weeks. The n-3 PUFA consumption and E₂ injection independently decreased the hepatic expressions of sterol regulatory element-binding protein 1, acetyl-CoA carboxylase 1, fatty acid synthase (FAS), and diacylglycerol acyltransferase 2 (DGAT2) (P < 0.05). There were interactions between n-3 PUFA consumption and E₂ injection on hepatic expression of FAS and DGAT2. In addition, n-3 PUFA consumption and E₂ injection up-regulated the expression of AMP-activated protein kinase (AMPK), phosphorylated AMPK, peroxisomal proliferator-activated receptor α, and carnitine palmitoyltransferase 1 in liver and skeletal muscle. E₂ injection increased the expression of estrogen receptor α and β in skeletal muscle and liver, but n-3 PUFA consumption increased the expression of both receptors only in skeletal muscle. The present study suggests that the hypotriglyceridemic effects of n-3 PUFA consumption and E₂ injection could be due to the down-regulation of hepatic TG synthesis and up-regulation of TG oxidation in liver and skeletal muscle in OVX rats.     

Influence of FADS polymorphisms on tracking of serum glycerophospholipid fatty acid concentrations and percentage composition in children

Background

Tracking of fatty acid (FA) contribution to plasma or serum lipids over time was shown in children and adults. However, the potential role of FADS gene variants has not been investigated.

Methods and Principal Findings

Serum GP FA composition of 331 children aged 2 and 6 years, participating in an ongoing birth cohort study, was analyzed. Correlation coefficients were estimated to describe FA tracking over 4 years and to assess the influence of FADS variants on tracking. We found low to moderate tracking (r = 0.12–0.49) of FA compositions and concentration between 2 and 6 years. Concentration changes of total monounsaturated FA and total saturated FA over time correlated closely (r = 0.79) but percentage values were unrelated (r = −0.02). Tracking for n-6 long chain polyunsaturated fatty acid (LC-PUFA) concentrations was lower in subjects homozygous for the major allele of FADS variants and higher in carriers of at least one minor allele, whereas for total n-3 LC-PUFA concentrations and compositions this was vice versa. For individual n-3 PUFA inconsistent results were found.

Conclusions and Significance

Serum GP FA composition shows low to moderate tracking over 4 years with a higher tracking for LC-PUFA metabolites than for their precursor FA. Serum PUFA levels and their tracking seem to be more influenced by lipid and lipoprotein metabolism than by FA specific pathways.     

A Metabolomic Analysis of Omega-3 Fatty Acid-Mediated Attenuation of Western Diet-Induced Nonalcoholic Steatohepatitis in LDLR -/- Mice

Background

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease and a risk factor for cirrhosis, hepatocellular carcinoma and liver failure. Previously, we reported that dietary docosahexaenoic acid (DHA, 22:6,n-3) was more effective than eicosapentaenoic acid (EPA, 20:5,n-3) at reversing western diet (WD) induced NASH in LDLR^-/- mice.

Methods

Using livers from our previous study, we carried out a global non-targeted metabolomic approach to quantify diet-induced changes in hepatic metabolism.

Results

Livers from WD + olive oil (WD + O)-fed mice displayed histological and gene expression features consistent with NASH. The metabolomic analysis of 320 metabolites established that the WD and n-3 polyunsaturated fatty acid (PUFA) supplementation had broad effects on all major metabolic pathways. Livers from WD + O-fed mice were enriched in saturated (SFA) and monounsaturated fatty acids (MUFA), palmitoyl-sphingomyelin, cholesterol, n-6 PUFA, n-6 PUFA-containing phosphoglycerolipids, n-6 PUFA-derived oxidized lipids (12-HETE) and depleted of C_20-22 n-3 PUFA-containing phosphoglycerolipids, C_20-22 n-3 PUFA-derived oxidized lipids (18-HEPE, 17,18-DiHETE) and S-lactoylglutathione, a methylglyoxal detoxification product. WD + DHA was more effective than WD + EPA at attenuating WD + O-induced changes in NASH gene expression markers, n-6 PUFA and oxidized lipids, citrate and S-lactosyl glutathione. Diet-induced changes in hepatic MUFA and sphingolipid content were associated with changes in expression of enzymes involved in MUFA and sphingolipid synthesis. Changes in hepatic oxidized fatty acids and S-lactoylglutathione, however, correlated with hepatic n-3 and n-6 C_20-22 PUFA content. Hepatic C_20-22 n-3 PUFA content was inversely associated with hepatic α-tocopherol and ascorbate content and positively associated with urinary F2- and F3-isoprostanes, revealing diet effects on whole body oxidative stress.

Conclusion

DHA regulation of hepatic SFA, MUFA, PUFA, sphingomyelin, PUFA-derived oxidized lipids and S-lactoylglutathione may explain the protective effects of DHA against WD-induced NASH in LDLR^-/- mice.     

N-3 long chain polyunsaturated fatty acids: a nutritional tool to prevent insulin resistance associated to type 2 diabetes and obesity?

n-3 long chain polyunsaturated fatty acids (n-3 LC-PUFA), mainly eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3), are present in mammal tissues both from endogenous synthesis from desaturation and elongation of 18:3 n-3 and/or from dietary origin (marine products and fish oils). In rodents in vivo, n-3 LC-PUFA have a protective effect against high fat diet induced insulin resistance. Such an effect is explained at the molecular level by the prevention of many alterations of insulin signaling induced by a high fat diet. Indeed, the protective effect of n-3 LC-PUFA results from the following: (a) the prevention of the decrease of phosphatidyl inositol 3' kinase (PI3 kinase) activity and of the depletion of the glucose transporter protein GLUT4 in the muscle; (b) the prevention of the decreased expression of GLUT4 in adipose tissue. In addition, n-3 LC-PUFA inhibit both the activity and expression of liver glucose-6-phosphatase which could explain the protective effect with respect to the excessive hepatic glucose output induced by a high fat diet. n-3 LC-PUFA also decrease muscle intramyofibrillar triglycerides and liver steatosis. This last effect results on the one hand, from a decreased expression of lipogenesis enzymes and of delta 9 desaturase (via a depleting effect on sterol response element binding protein 1c (SREBP-1c). On the other hand, n-3 LC-PUFA stimulate fatty acid oxidation in the liver (via the activation of peroxisome proliferator activated receptor alpha (PPAR-alpha)). In patients with type 2 diabetes, fish oil dietary supplementation fails to reverse insulin resistance for unclear reasons, but systematically decreases plasma triglycerides. Conversely, in healthy humans, fish oil has many physiological effects. Indeed, fish oil reduces insulin response to oral glucose without altering the glycaemic response, abolishes extraggression at times of mental stress, decreases the activation of sympathetic activity during mental stress and also decreases plasma triglycerides. These effects are encouraging in the perspective of prevention of insulin resistance but further clinical and basic studies must be designed to confirm and complete our knowledge in this field.     

Cloning and functional characterisation of a fatty acyl elongase from southern bluefin tuna (Thunnus maccoyii)

The synthesis of long chain polyunsaturated fatty acids (LCPUFA), such as eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), involves fatty acyl desaturase and elongase enzymes. The marine fish species southern bluefin tuna (SBT) can accumulate large quantities of omega-3 (n-3) LCPUFA in its flesh but their capacity to synthesize EPA and DHA is uncertain. A cDNA, sbtElovl5, encoding a putative fatty acyl elongase was amplified from SBT liver tissue. The cDNA included an open reading frame (ORF) encoding 294 amino acids. Sequence comparisons and phylogenetic analyses revealed a high level of sequence conservation between sbtElovl5 and fatty acyl elongase sequences from other fish species. Heterologous expression of the sbtElovl5 ORF in Saccharomyces cerevisiae confirmed that it encoded a fatty acyl elongase capable of elongating C_18/20 polyunsaturated fatty acid (PUFA) substrates, but not C₂₂ PUFA substrates. For the first time in an Elovl5, the substrate competition occurring in nature was investigated. Higher activity towards n-3 PUFA substrates than omega-6 (n-6) PUFA substrates was exhibited, regardless of substrate chain length. The sbtElovl5 preferentially elongated 18:4n-3 and 18:3n-6 rather than 20:5n-3 and 20:4n-6. The sbtElovl5 enzyme also elongated saturated and monounsaturated fatty acids.     

Effect of a linseed diet on lipogenesis, fatty acid composition and stearoyl-CoA-desaturase in rabbits

The aim of the study was to examine the effect of a linseed diet on meat quality and on lipogenesis in rabbits. Twelve rabbits were fed a control or a linseed diet. There was no diet effect on growth, food consumption, carcass characteristics and meat ultimate pH and colour. Feeding the linseed diet increased the n-3 polyunsaturated fatty acids (PUFA) levels in perirenal and interscapular fats, in the Longissimus dorsi muscle and in the liver. The linseed diet produced lower linoleic acid/α-linolenic acid ratios in adipose tissues and in the Longissimus dorsi muscle, but not in the liver. Diet did not affect lipogenic enzyme activities in the Longissimus dorsi muscle, whereas the linseed diet decreased the lipogenic potential in perirenal and interscapular fats, and in the liver. Feeding rabbits with a high n-3 PUFA diet led to a decrease in the oxidative stability of perirenal fat and the Longissimus dorsi muscle, and to an inhibition of stearoyl-CoA-desaturase activity in liver and in adipose tissues, but not in muscle.     

Fatty acid compositional changes during the embryonic development of the swimming crab,Portunus pelagicus (Portunidae: Decapoda)

Abstract

The fatty acid composition, moisture, and total lipid of the eggs from the swimming crab, Portunus pelagicus, at three different embryonic stages (within 24 h, during the eye placode stage and the final heart beat stage), were measured. Results showed that the moisture and lipid content significantly increased and decreased (p < 0.05), respectively, as the stages progressed. The most prevalent fatty acids that were initially deposited included C16:0, C18:1n-9, and C18:0, while the most consumed fatty acids were C22:5n-6, C22:5n-3, and C20:1n-7. Among the major fatty acid groups, polyunsaturated fatty acids (PUFA) and long-chain PUFA (LC-PUFA) were consumed more than saturated fatty acids and significantly more (p < 0.05) than monounsaturated fatty acids (p < 0.05). Meanwhile, n-3 PUFA was deposited in significantly higher amounts (p < 0.05) than n-6 PUFA, but both were consumed at similar amounts at 43.4% and 41.3%, respectively. The relatively low amount of C20:5n-3 and C22:6n-3 consumption may indicate these fatty acids were conserved, while the essential fatty acids C18:3n-3 and C18:3n-6 were consumed at high amounts. These findings may have implications for broodstock nutrition in order to formulate a well-balanced diet.     

Comparative effects of well-balanced diets enriched in α-linolenic or linoleic acids on LC-PUFA metabolism in rat tissues

The intake of the essential fatty acid precursor α-linolenic acid (ALA) contributes to ensure adequate n-3 long-chain polyunsaturated fatty acid (LC-PUFA) bioavailability. Conversely, linoleic acid (LA) intake may compromise tissue n-3 PUFA status as its conversion to n-6 LC-PUFA shares a common enzymatic pathway with the n-3 family. This study aimed to measure dietary ALA and LA contribution to LC-PUFA biosynthesis and tissue composition. Rats were fed with control or experimental diets moderately enriched in ALA or LA for 8 weeks. Liver Δ6- and Δ5-desaturases were analyzed and FA composition was determined in tissues (red blood cells, liver, brain and heart). Hepatic Δ6-desaturase activity was activated with both diets, and Δ5-desaturase activity only with the ALA diet. The ALA diet led to higher n-3 LC-PUFA composition, including DHA in brain and heart. The LA diet reduced n-3 content in blood, liver and heart, without impacting n-6 LC-PUFA composition. At levels relevant with human nutrition, increasing dietary ALA and reducing LA intake were both beneficial in increasing n-3 LC-PUFA bioavailability in tissues.     

Δ-6 Desaturase Substrate Competition: Dietary Linoleic Acid (18∶2n-6) Has Only Trivial Effects on α-Linolenic Acid (18∶3n-3) Bioconversion in the Teleost Rainbow Trout

It is generally accepted that, in vertebrates, omega-3 (n-3) and omega-6 (n-6) poly-unsaturated fatty acids (PUFA) compete for Δ-6 desaturase enzyme in order to be bioconverted into long-chain PUFA (LC-PUFA). However, recent studies into teleost fatty acid metabolism suggest that these metabolic processes may not conform entirely to what has been previously observed in mammals and other animal models. Recent work on rainbow trout has led us to question specifically if linoleic acid (LA, 18∶2n-6) and α-linolenic acid (ALA, 18∶3n-3) (Δ-6 desaturase substrates) are in direct competition for access to Δ-6 desaturase. Two experimental diets were formulated with fixed levels of ALA, while LA levels were varied (high and low) to examine if increased availability of LA would result in decreased bioconversion of ALA to its LC-PUFA products through substrate competition. No significant difference in ALA metabolism towards n-3 LC-PUFA was exhibited between diets while significant differences were observed in LA metabolism towards n-6 LC-PUFA. These results are evidence for minor if any competition between substrates for Δ-6 desaturase, suggesting that, paradoxically, the activity of Δ-6 desaturase on n-3 and n-6 substrates is independent. These results call for a paradigm shift in the way we approach teleost fatty acid metabolism. The findings are also important with regard to diet formulation in the aquaculture industry as they indicate that there should be no concern for possible substrate competition between 18∶3n-3 and 18∶2n-6, when aiming at increased n-3 LC-PUFA bioconversion in vivo.     

Dietary omega-6 fatty acid lowering increases bioavailability of omega-3 polyunsaturated fatty acids in human plasma lipid pools

BackgroundDietary linoleic acid (LA, 18:2n-6) lowering in rats reduces n-6 polyunsaturated fatty acid (PUFA) plasma concentrations and increases n-3 PUFA (eicosapentaenoic (EPA) and docosahexaenoic acid (DHA)) concentrations.ObjectiveTo evaluate the extent to which 12 weeks of dietary n-6 PUFA lowering, with or without increased dietary n-3 PUFAs, alters unesterified and esterified plasma n-6 and n-3 PUFA concentrations in subjects with chronic headache.DesignSecondary analysis of a randomized trial. Subjects with chronic headache were randomized for 12 weeks to (1) average n-3, low n-6 (L6) diet; or (2) high n-3, low n-6 LA (H3–L6) diet. Esterified and unesterified plasma fatty acids were quantified at baseline (0 weeks) and after 12 weeks on a diet.ResultsCompared to baseline, the L6 diet reduced esterified plasma LA and increased esterified n-3 PUFA concentrations (nmol/ml), but did not significantly change plasma arachidonic acid (AA, 20:4n-6) concentration. In addition, unesterified EPA concentration was increased significantly among unesterified fatty acids. The H3–L6 diet decreased esterified LA and AA concentrations, and produced more marked increases in esterified and unesterified n-3 PUFA concentrations.ConclusionDietary n-6 PUFA lowering for 12 weeks significantly reduces LA and increases n-3 PUFA concentrations in plasma, without altering plasma AA concentration. A concurrent increase in dietary n-3 PUFAs for 12 weeks further increases n-3 PUFA plasma concentrations and reduces AA.     

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.     

Comparison of muscle fatty acid composition and lipid stability in lambs stall-fed or pasture-fed alfalfa with or without sainfoin pellet supplementation

Currently, consumers are increasingly interested in obtaining high-quality and healthy lamb meat. Compared to grain-based diets, dietary forage legumes such as alfalfa and condensed tannin (CT)-rich sainfoin increase the levels of polyunsaturated fatty acids (PUFAs) that are beneficial for health in lamb meat thanks to their high content in PUFA and/or their impact on ruminal biohydrogenation. However, they can therefore adversely affect its oxidative stability. Thus, the impact of dietary forage legumes on lamb longissimus thoracis (LT) muscle FA composition and their stability to peroxidation was studied in 36 Romane lambs grazing alfalfa (AF; n = 12) or alfalfa plus daily supplementation with CT-rich sainfoin pellets (AS; n = 12; 15 g DM/kg BW, 42 g CT/kg DM) or stall-fed concentrate and grass hay indoors (SI; n = 12). Lambs were slaughtered at a mean age of 162 ± 8.0 days after an average experimental period of 101 ± 8.1 days. Forage legumes-grazing lambs outperformed SI lambs in LT nutritional quality, with more conjugated linoleic acids and n-3 PUFAs, especially 18:3n-3, eicosapentaenoic and docosahexaenoic acids (P < 0.001), and thus lower n-6 PUFA/n-3 PUFA and 18:2 n-6/18:3 n-3 ratios (P < 0.001). Peroxidizability index was higher (P < 0.001) in LT muscle of forage legumes-grazing lambs. Concurrently, two endogenous antioxidant enzyme activities, superoxide dismutase and glutathione peroxidase, were, respectively, similar and lower (P < 0.001) for forage legumes-grazing compared with SI lambs. A lower vitamin E level in SI lambs compared with forage legumes-grazing lambs (1.0 v. 3.8 mg/g, P < 0.001) could explain that malondialdehyde content, a marker of lipid oxidation intensity, was 0.63 µg/g in SI after 8 days in aerobic packaging conditions, whereas it remaining steady at 0.16 µg/g in forage legumes-grazing lambs. Dietary forage alfalfa thus improved FA composition of lamb LT muscle and their stability to oxidation when compared to SI lambs. However, supplementation of alfalfa-grazing lambs with CT-rich sainfoin pellets did not affect the nutritional quality of LT muscle FAs.     

Biochemical characterization of polyunsaturated fatty acid synthesis in Schizochytrium: Release of the products as free fatty acids

In marine bacteria and some thraustochytrids (marine stramenopiles) long-chain polyunsaturated fatty acids (LC-PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are produced de novo by PUFA synthases. These large, multi-domain enzymes carry out the multitude of individual reactions required for conversion of malonyl-CoA to the final LC-PUFA products. Here we report on the release of fatty acids from the PUFA synthase found in Schizochytrium, a thraustochytrid that has been developed as a commercial source for DHA-enriched biomass and oil. Data from in vitro activity assays indicate that the PUFAs are released from the enzyme as free fatty acids (FFAs). Addition of ATP and Mg²⁺ to in vitro assays facilitates appearance of radiolabel from ¹⁴C-malonyl-CoA in a triacylglycerol fraction, suggesting the involvement of acyl-CoA synthetases (ACS). Furthermore, addition of triascin C, an inhibitor of ACSs, to the assays blocks this conversion. When the Schizochytrium PUFA synthase is expressed in Escherichia coli, the products of the enzyme accumulate as FFAs, suggesting that the thioesterase activity required for fatty acid release is an integral part of the PUFA synthase.