Plasma Phospholipid Concentrations Research Articles

Is there a role for essential fatty acids in osteoporosis?

Inflammatory markers are inversely associated with bone density, geometry, and strength in postmenopausal women, and elderly subjects suggesting that osteoporosis is a low-grade systemic inflammatory condition. But glucocorticoids that are potent anti-inflammatory compounds instead of arresting/preventing osteoporosis induce osteoporosis. These results indicate that IL-6 and TNF-α, post-menopausal state, and steroids produce osteoporosis by an unidentified mechanism. Pro-inflammatory cytokines, estrogen, and steroids bring about their actions by influencing the metabolism of essential fatty acids (EFAs). I propose that EFAs and their metabolites act as second messengers of actions of corticosteroids, cytokines, and estrogen. This implies that EFAs are of benefit in the prevention and management of osteoporosis. This argument is supported by the observation that plasma phospholipid content of unsaturated fatty acids is decreased in those with osteoporosis. The reports that long-chain metabolites of EFAs including arachidonic acid, docosahexaenoic acid and eicosapentaenoic acid, and lipoxin A4 are of benefit in the prevention and management of osteoporosis lends further support to this proposal.

Sex differences in lipid mediators derived from omega-3 fatty acids in older individuals with low-grade chronic inflammation.

The rate of cardiovascular disease (CVD) death is higher in men than women before age 50 y, but the gap between sexes significantly narrows after menopause. Lipid mediators derived from EPA, DHA and AA play a role in inflammation and CVD. The aim of our study was to assess whether plasma concentrations of these lipid mediators differ between postmenopausal women and men. Twelve postmenopausal women and 9 men with low-grade chronic inflammation completed a randomized, double-blind, crossover study consisting of a 4-week lead-in placebo phase (3 g/d high-oleic acid sunflower oil) followed by randomization to either 3 g/d DHA or 3 g/d EPA for 10 weeks and crossover for additional 10 weeks, separated by a washout phase. Plasma phospholipid content of EPA, DHA and AA and plasma concentrations of their derived lipid mediators were measured at the end of the placebo lead-in phase (baseline) and the DHA and EPA supplementation phases. There were no sex differences in plasma phospholipid EPA, DHA and AA at baseline and after DHA and EPA supplementation. However, plasma concentrations of lipid mediators derived from EPA, DHA and AA via 15-lipoxygenase were lower in postmenopausal women than men, especially after supplementation. Sex differences in EPA- and DHA-derived lipid mediators with anti-inflammatory and pro-resolving actions may partly explain the faster rise in CVD in postmenopausal women than age-matched men.

Exploring the Interactions between Obesity and Diabetes: Implications for Understanding Metabolic Dysregulation in a Saudi Arabian Adult Population.

The rising prevalence of obesity in Saudi Arabia is a major contributor to the nation's high levels of cardiometabolic diseases such as type 2 diabetes. To assess the impact of obesity on the diabetic metabolic phenotype presented in young Saudi Arabian adults, participants (n = 289, aged 18-40 years) were recruited and stratified into four groups: healthy weight (BMI 18.5-24.99 kg/m2) with (n = 57) and without diabetes (n = 58) or overweight/obese (BMI > 24.99 kg/m2) with (n = 102) and without diabetes (n = 72). Distinct plasma metabolic phenotypes associated with high BMI and diabetes were identified using nuclear magnetic resonance spectroscopy and ultraperformance liquid chromatography mass spectrometry. Increased plasma glucose and dysregulated lipoproteins were characteristics of obesity in individuals with and without diabetes, but the obesity-associated lipoprotein phenotype was partially masked in individuals with diabetes. Although there was little difference between diabetics and nondiabetics in the global plasma LDL cholesterol and phospholipid concentration, the distribution of lipoprotein particles was altered in diabetics with a shift toward denser and more atherogenic LDL5 and LDL6 particles, which was amplified in the presence of obesity. Further investigation is warranted in larger Middle Eastern populations to explore the dysregulation of metabolism driven by interactions between obesity and diabetes in young adults.

Plasma essential fatty acid on hospital admission is a marker of COVID-19 disease severity

It is important for allocation of resources to predict those COVID patients at high risk of dying or organ failure. Early signals to initiate cellular events of host immunity can be derived from essential fatty acid metabolites preceding the cascade of proinflammatory signals. Much research has focused on understanding later proinflammatory responses. We assessed if remodelling of plasma phospholipid content of essential fatty acids by the COVID-19 virus provides early markers for potential death and disease severity. Here we show that, at hospital admission, COVID-19 infected subjects who survive exhibit higher proportions of C20:4n-6 in plasma phospholipids concurrent with marked proinflammatory cytokine elevation in plasma compared to healthy subjects. In contrast, more than half of subjects who die of this virus exhibit very low C18:2n-6 and C20:4n-6 content in plasma phospholipids on hospital admission compared with healthy control subjects. Moreover, in these subjects who die, the low level of primary inflammatory signals indicates limited or aberrant stimulation of host immunity. We conclude that COVID-19 infection results in early fundamental remodelling of essential fatty acid metabolism. In subjects with high mortality, it appears that plasma n-6 fatty acid content is too low to stimulate cellular events of host immunity.

Assessing the validity of plasma phospholipid fatty acids as biomarkers of dairy fat intake using data from a randomized controlled intervention trial

Plasma phospholipid pentadecanoic acid (C15:0), heptadecanoic acid (C17:0), and trans-palmitoleic acid (trans-C16:1n-7) are correlates of dairy fat intake. However, their relative concentrations may be influenced by other endogenous factors, such as liver fat content, and their validity as biomarkers of dairy fat intake has yet to be established. We investigated whether liver fat content modifies relations between concentrations of C15:0, C17:0, and trans-C16:1n-7 (alone and in combination with iso-C17:0) and known dairy fat intake in the context of a randomized controlled intervention study. We further examined the proportion of dairy fat intake explained by these fatty acids on their own and when considering liver fat content. We used data from a 12-wk intervention trial in which participants (n=62) consumed diets limited in dairy (0.3g/d of dairy fat), rich in low-fat dairy (8.7g/d of dairy fat), or rich in full-fat dairy (28.5g/d of dairy fat). We used linear regression models to examine relations between relative fatty acid concentrations and grams per day of dairy fat intake, liver fat percentage, and their interaction. Only trans-C16:1n-7 in isolation (β: 0.0004±0.0002, P=0.03) and combined with iso-C17:0 (β: 0.002±0.0005, P<0.0001) were consistently positively associated with dairy fat intake regardless of liver fat content. Trans-C16:1n-7 combined with iso-C17:0 also explained the greatest proportion of variation (35.4%) in dairy fat intake. C15:0 and C17:0 were not associated with dairy fat intake after adjusting for liver fat and were predicted to be higher in relation to increased dairy fat intake only among individuals with elevated liver fat. The potential for liver fat to affect relative plasma phospholipid concentrations of C15:0 and C17:0 raises questions about their validity as biomarkers of dairy fat intake. Of the fatty acid measures tested, trans-C16:1n-7 combined with iso-C17:0, especially with adjustment of liver fat, age, and sex, may provide the most robust estimate of dairy fat consumption.

Dietary intake and plasma phospholipid concentrations of saturated, monounsaturated and trans fatty acids and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort.

Epidemiologic studies examining the association between specific fatty acids and colorectal cancer (CRC) risk are inconclusive. We investigated the association between dietary estimates and plasma levels of individual and total saturated (SFA), monounsaturated (MUFA), industrial-processed trans (iTFA), and ruminant-sourced trans (rTFA) fatty acids, and CRC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Baseline fatty acid intakes were estimated in 450 112 participants (6162 developed CRC, median follow-up=15 years). In a nested case-control study, plasma phospholipid fatty acids were determined by gas chromatography in 433 colon cancer cases and 433 matched controls. Multivariable-adjusted hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were computed using Cox and conditional logistic regression, respectively. Dietary total SFA (highest vs lowest quintile, HRQ5vsQ1 =0.80; 95%CI:0.69-0.92), myristic acid (HRQ5vsQ1 =0.83, 95%CI:0.74-0.93) and palmitic acid (HRQ5vsQ1 =0.81, 95%CI:0.70-0.93) were inversely associated with CRC risk. Plasma myristic acid was also inversely associated with colon cancer risk (highest vs lowest quartile, ORQ4vsQ1 =0.51; 95%CI:0.32-0.83), whereas a borderline positive association was found for plasma stearic acid (ORQ4vsQ1 =1.63; 95%CI:1.00-2.64). Dietary total MUFA was inversely associated with colon cancer (per 1-SD increment, HR1-SD =0.92, 95%CI: 0.85-0.98), but not rectal cancer (HR1-SD =1.04, 95%CI:0.95-1.15, Pheterogeneity =0.027). Dietary iTFA, and particularly elaidic acid, was positively associated with rectal cancer (HR1-SD =1.07, 95%CI:1.02-1.13). Our results suggest that total and individual saturated fatty acids and fatty acids of industrial origin may be relevant to the aetiology of CRC. Both dietary and plasma myristic acid levels were inversely associated with colon cancer risk, which warrants further investigation.

Twenty six-week repeat dose oral rat toxicity study of cizolirtine, a substance-P and calcitonin gene-related peptide release modulator

Cizolirtine, a substance-P and calcitonin gene-related peptide release modulator developed for the treatment of pain and urinary incontinence, was orally administered for 26-weeks to rats at dosages of 20, 60 and 200 mg/kg/day. Clinical signs were limited to post-dosing salivation and brown staining on head and muzzle. There were slight decreases in bodyweight gain and slight increases in water consumption among cizolirtine-treated animals. Slight increases in plasma alkaline phosphatase activity, and cholesterol and phospholipid concentrations were observed in mid- and/or high-dose animals. Low urinary volume, pH and sodium and potassium outputs were observed after 12-weeks, and low urinary pH, low sodium and high potassium outputs at end of treatment. Increased relative (to bodyweight) liver weight was observed in high-dose animals. Treated males and high-dose females showed a dose-related increase in the incidence and severity of periacinar hepatocytic hypertrophy and midzonal/periacinar hepatocytic fat vacuolization. Increased incidences of hepatic clear cell foci were observed in all cizolirtine-treated male groups and, to a lesser extent, in treated females. Ovaries of treated females showed a dose-dependent increased incidence of absent corpora lutea and, occasionally, follicular cysts. The dosages of 20 and 60 mg/kg/day were considered as the No-Observed-Adverse-Effect Levels for males and females, respectively.

Phytol supplementation alters plasma concentrations of formate, amino acids, and lipid metabolites in sheep

The phytol moiety in chlorophyll molecules acts as an agonist of peroxisome proliferator-activated receptor-α in monogastric animals. The current study aimed to clarify the effects of dietary supplementation with phytol on the plasma concentrations of formate and amino acids related to one-carbon (1C) donors and its effects on lipid metabolism in sheep. Four mature sheep were fed with a mixed ration (metabolizable energy, 10.7 MJ/kg DM; CP, 150 g/kg DM) comprising barley, rice bran, soybean meal, and oat hay at 1.5 times maintenance metabolizable energy for three consecutive 14-day experimental periods. The first and third periods served as controls without phytol supplementation, while in the second period, phytol was added to the mixed ration at 12 g/kg of dietary DM per day. In each period, feces, urine, and jugular blood samples were collected. Dry matter intake in relation to metabolic BW was slightly lower (P < 0.01) in the first period than the second and third periods but did not differ between the latter two periods. Dry matter digestibility was slightly reduced (P = 0.05) by the phytol treatment. Nitrogen (N) intake and retention showed similar trends to DM intake, but urinary N was unchanged among the periods. Plasma cholesterol and phospholipid concentrations decreased during the phytol treatment period, while triglyceride concentration increased (P < 0.05). In the phytol treatment period, the plasma concentrations of serine and glycine (1C donors) increased, but the glutamate level decreased (P < 0.01). Plasma concentrations of formate and methionine increased (P < 0.01) from the first control period to the phytol supplementation period, but homocysteine and cysteine (intermediate and by-product of the methionine cycle) levels were unchanged among the treatment periods. In conclusion, dietary phytol affects lipid metabolism as well as amino acid metabolism and 1C donors in sheep. These effects may be associated with the activity of phytol as an agonist of the nuclear receptors, although this needs further investigation.

Genetically predicted plasma phospholipid arachidonic acid concentrations and 10 site-specific cancers in UK biobank and genetic consortia participants: A mendelian randomization study

Arachidonic acid (AA) is metabolized by cyclooxygenases and lipoxygenases to pro-inflammatory eicosanoids, which according to experimental research modulate tumor cell proliferation, differentiation, and apoptosis. We employed the Mendelian randomization design to test the hypothesis that higher plasma phospholipid AA concentrations are associated with increased risk of 10 site-specific cancers. Two genetic variants associated with plasma phospholipid concentrations of AA (rs174547 in FADS1 [P=3.0×10-971] and rs16966952 in PDXDC1 [P=2.4×10-10]) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium were used as genetic instruments. The associations of those variants with cancer were taken from the UK Biobank (n=367,643), FinnGen consortium (n=135,638), International Lung Cancer Consortium (n=27,209), Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium (n=140,254), Breast Cancer Association Consortium (n=228,951), Ovarian Cancer Association Consortium (n=66,450), and BioBank Japan (n=212,453). Higher genetically predicted plasma phospholipid AA concentrations were associated with increased risk of colorectal and lung cancer. Results were consistent across data sources and variants. The combined odds ratios per standard deviation increase of AA concentrations were 1.08 (95% CI 1.05-1.11; P=6.3×10-8) for colorectal cancer and 1.07 (95%CI 1.05-1.10; P=3.5×10-7) for lung cancer. Genetically predicted AA concentrations had a suggestive positive association with esophageal cancer (odds ratio 1.09; 95% CI 1.02-1.17; P=0.016) but were not associated with cancers of the stomach, pancreas, bladder, prostate, breast, uterus, or ovary. These results indicate that AA may be implicated in the development of colorectal and lung cancer and possibly esophageal cancer. Treatments with plasma AA-lowering properties should be evaluated for clinical benefit.

Plasma Phospholipid Fatty Acids and Breast Cancer Risk in Alberta’s Tomorrow Project

Abstract Objectives It is estimated that lifestyle factors, such as dietary intake, contribute up to 21% of all breast cancer (BC) cases. High dietary intakes of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) have been associated with a reduced incidence of BC. Dietary intake of n-3 LCPUFA typically correlate with blood fatty acid concentrations, but the relationship between blood fatty acid concentrations and BC risk has not yet been established. We hypothesized that higher plasma phospholipid (PL) content of n-3 LCPUFAs would be associated with a reduced risk of BC. Methods Plasma samples and relevant covariables were obtained from 614 age-matched women (203 with BC/411 control) from a nested case-control within Alberta's Tomorrow Project. PL fatty acid concentration and relative % composition were determined from baseline plasma samples (collected 9–16 years pre-BC diagnosis). Principal component analysis was employed to determine predictive models for fatty acid clusters. Conditional logistic regression models controlled for covariates were used to assess the relative risk of BC (odds ratio-OR) by fatty acid content. Sub-group analyses by menopausal status and BMI at baseline were also performed. Results When adjusted for BMI and menopausal status, individual fatty acids, including linoleic acid (OR = 1.75, 95% confidence interval (CI) = 1.08,2.84, P &amp;lt; 0.04) and arachidonic acid (OR = 1.60, 95% CI = 1.03,2.49, P &amp;lt; 0.04), were positively associated with BC risk. However, composite analysis of grouped fatty acids were found to be stronger indicators of risk – total PUFA (µg/mL; OR = 2.25, 95% CI = 1.4,3.44, P &amp;lt; 0.001), total n-6 PUFA (OR = 2.11, 95% CI = 1.32,3.36, P &amp;lt; 0.002), and total n-3 PUFA (OR = 1.57, 95% CI = 1.06,2.32, P &amp;lt; 0.02), were independent predictors of BC risk. Conclusions In contrast to epidemiological dietary evidence, this study found an increased risk of BC with higher plasma concentrations of n-3 LCPUFA. However, the absolute n-3 concentration in this population was low, and therefore a second cohort is being assessed to validate these results. Overall, this study suggests that risk of BC cannot be predicted by isolated fatty acid blood concentrations, but that the balance of different fatty acids or the combination of n-3 and n-6 fatty acids may be a better predictor of BC. Funding Sources Funded by Women and Children's Health Research Institute.

Decreased plasma phospholipid concentrations and increased acid sphingomyelinase activity are accurate biomarkers for community-acquired pneumonia

BackgroundThere continues to be a great need for better biomarkers and host-directed treatment targets for community-acquired pneumonia (CAP). Alterations in phospholipid metabolism may constitute a source of small molecule biomarkers for acute infections including CAP. Evidence from animal models of pulmonary infections and sepsis suggests that inhibiting acid sphingomyelinase (which releases ceramides from sphingomyelins) may reduce end-organ damage.MethodsWe measured concentrations of 105 phospholipids, 40 acylcarnitines, and 4 ceramides, as well as acid sphingomyelinase activity, in plasma from patients with CAP (n = 29, sampled on admission and 4 subsequent time points), chronic obstructive pulmonary disease exacerbation with infection (COPD, n = 13) as a clinically important disease control, and 33 age- and sex-matched controls.ResultsPhospholipid concentrations were greatly decreased in CAP and normalized along clinical improvement. Greatest changes were seen in phosphatidylcholines, followed by lysophosphatidylcholines, sphingomyelins and ceramides (three of which were upregulated), and were least in acylcarnitines. Changes in COPD were less pronounced, but also differed qualitatively, e.g. by increases in selected sphingomyelins. We identified highly accurate biomarkers for CAP (AUC ≤ 0.97) and COPD (AUC ≤ 0.93) vs. Controls, and moderately accurate biomarkers for CAP vs. COPD (AUC ≤ 0.83), all of which were phospholipids. Phosphatidylcholines, lysophosphatidylcholines, and sphingomyelins were also markedly decreased in S. aureus-infected human A549 and differentiated THP1 cells. Correlations with C-reactive protein and procalcitonin were predominantly negative but only of mild-to-moderate extent, suggesting that these markers reflect more than merely inflammation. Consistent with the increased ceramide concentrations, increased acid sphingomyelinase activity accurately distinguished CAP (fold change = 2.8, AUC = 0.94) and COPD (1.75, 0.88) from Controls and normalized with clinical resolution.ConclusionsThe results underscore the high potential of plasma phospholipids as biomarkers for CAP, begin to reveal differences in lipid dysregulation between CAP and infection-associated COPD exacerbation, and suggest that the decreases in plasma concentrations are at least partially determined by changes in host target cells. Furthermore, they provide validation in clinical blood samples of acid sphingomyelinase as a potential treatment target to improve clinical outcome of CAP.

Comparing docosahexaenoic acid (DHA) concomitant with neoadjuvant chemotherapy versus neoadjuvant chemotherapy alone in the treatment of breast cancer (DHA WIN): protocol of a double-blind, phase II, randomised controlled trial

IntroductionNeoadjuvant chemotherapy for breast cancer treatment is prescribed to facilitate surgery and provide confirmation of drug-sensitive disease, and the achievement of pathological complete response (pCR) predicts improved long-term outcomes. Docosahexaenoic...

Marine n-3 PUFA, heart rate variability and ventricular arrhythmias in patients on chronic dialysis: a cross-sectional study.

Marine n-3 PUFA may improve autonomic dysfunction by an increase in heart rate variability (HRV) and may reduce the risk of malignant ventricular arrhythmias. Only a few smaller studies have examined such effects in patients on chronic dialysis, who often have autonomic dysfunction and a high risk of sudden cardiac death, which accounts for almost 30 % of all deaths. This cross-sectional study investigated the association between the plasma phospholipid content of n-3 PUFA and 24-h HRV or ventricular arrhythmias in patients on chronic dialysis. A 48-h Holter monitoring was performed on 169 patients on in-centre dialysis (83 %), home haemodialysis (10 %) or peritoneal dialysis (7 %) obtaining data on arrhythmias (n 152) and 24-h HRV (n 135). The mean overall HRV (standard deviation of normal intervals (SDNN)) was low and 71 % had a reduced overall HRV (SDNN<100 ms) indicating autonomic dysfunction. No significant associations between plasma phospholipid content of total marine n-3 PUFA, EPA (22 : 5n-3) or DHA (22 : 6n-3) and time-domain or frequency-domain HRV were detected in crude or adjusted linear regression analysis. However, a higher plasma phospholipid content of DHA was associated with a significantly lower proportion of patients with ventricular tachycardia (higher DHA-tertile: 9 % v. lower DHA-tertile: 28 %, P=0·02). In conclusion, the content of marine n-3 PUFA in plasma phospholipids was not associated with 24-h HRV, but a higher plasma phospholipid content of DHA was associated with a lower occurrence of ventricular tachycardia suggesting an antiarrhythmic effect of marine n-3 PUFA in patients on chronic dialysis.

Enhanced Lipid Profile in Plasma and Erythrocytes of Hypertensive Type-2-Diabetes Mellitus Subjects in South-Western Nigeria

The growing burden of hypertension and type 2 diabetes mellitus (T2DM) in Nigeria and related cardiovascular complications is becoming a public health concern. Cardiovascular risk factors were evaluated in control subjects (n=150) and patients (n=470) [hypertensive nondiabetics (n=179), normotensive diabetics (n=132), hypertensive diabetics (n=159)] attending at the Medical Out-Patient Clinic of the State Hospital, Abeokuta, Nigeria. Cholesterol, triacylglycerols and phospholipids were determined spectrophotometrically in plasma, erythrocytes and lipoproteins. The presence of either or both diseases resulted in significant (p&lt;0.05) perturbations in blood lipids of the male and female patients. Dyslipidemia was characterised by increased concentrations of cholesterol and triacylglycerols in plasma, erythrocytes, low density lipoprotein (LDL) and very low-density lipoprotein (VLDL). The increase was more pronounced in hypertensive diabetics. High density lipoprotein (HDL) cholesterol values of the male and female patients were between 35% to 43% and 37% to 43% respectively lower than their control counterparts, while that of HDL triacylglycerols was between 8% to 10% and 6% to 23% respectively lower than their control counterparts. Plasma and erythrocyte phospholipid content increased significantly (p&lt;0.05) in all the patients when compared with their control counterparts except in the erythrocytes of the normotensive diabetic male, where significant decrease was observed. Our findings suggest that enhanced hypercholesterolemia, hypertriacylglycerolemia and hyperphospholipidemia in plasma and erythrocytes may be responsible for increased cardiovascular complications in the comorbidity since the combined dyslipidemia are more pronounced in comorbidity of hypertension and T2DM than when either of the two conditions occurs in isolation.Bangladesh J Med Biochem 2017; 10(2): 45-57

Amelioration of streptozotocin-induced type 2 diabetes mellitus in Wistar rats by arachidonic acid

Traditionally arachidonic acid (AA, 20:4 n-6) is considered as a pro-inflammatory molecule since it forms precursor to prostaglandins (PGs), leukotrienes (LTs) and thromboxanes (TXs) that have pro-inflammatory actions. Type 2 diabetes mellitus (type 2 DM) is considered as a low-grade systemic inflammatory condition in which circulating PGs and LTs are increased. Streptozotocin (STZ)-induced type 2 DM is used as a model of human type 2 DM in which peripheral insulin resistance, increased plasma interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and hyperglycemia occurs. In the present study, we observed that oral supplementation of AA prevented STZ-induced type 2 DM in Wistar rats by restoring hyperglycemia, plasma levels of TNF-α and IL-6; adipose tissue NF-kB and lipocalin 2 (LPCLN2) and pancreatic tissue NF-kB and 5- and 12- lipoxygenase enzymes to normal. AA treatment enhanced insulin sensitivity and plasma lipoxin A4 (LXA4) levels, a potent anti-inflammatory molecule derived from AA. These results are supported by our previous studies wherein it was noted that plasma phospholipid content of AA and circulating LXA4 levels are low in those with type 2 DM. In a preliminary study, we also noted that high-fat-diet (HFD)-induced type 2 DM in Wistar rats can be prevented by oral supplementation of AA. These results suggest AA has anti-inflammatory and anti-diabetic actions by enhancing the production of its anti-inflammatory metabolite LXA4.

Docosahexaenoic Acid Supplementation is Not Anti-Inflammatory in Adipose Tissue of Healthy Obese Postmenopausal Women.

Adipose tissue inflammation is associated with obesity comorbidities. Reducing such inflammation may ameliorate these comorbidities. n-3 fatty acids have been reported to have anti-inflammatory properties in obesity, which may modulate this inflammatory state. In the current study a 1 gram per day oral supplement of the n-3 fatty acid docosahexaenoic acid (DHA) was administered for 12 weeks to 10 grade 1-2 obese postmenopausal women and markers of adipose tissue and systemic inflammation measured and compared before and after supplementation. DHA administration resulted in approximately a doubling of plasma and red cell phospholipid and adipose tissue DHA content but no change in systemic markers of inflammation, such as circulating C-reactive protein (CRP) or interleukins (IL) 6, 8 and 10 (IL-6, IL-8, IL-10). DHA supplementation did not alter the adipose tissue marker of inflammation crown-like structure density nor did it affect any gene expression pathways, including anti-inflammatory, hypoxic and lipid metabolism pathways. The obese postmenopausal women studied were otherwise healthy, which leads us to suggest that in such women DHA supplementation is not an effective means for reducing adipose tissue or systemic inflammation. Further testing is warranted to determine if n-3 fatty acids may ameliorate inflammation in other, perhaps less healthy, populations of obese individuals.

Plasma fatty acid patterns during pregnancy and child's growth, body composition, and cardiometabolic health: The Generation R Study

Exposure to different concentrations of fatty acids during fetal life may affect growth and metabolism. However, most studies examined individual fatty acids, whereas concentrations highly correlate and may interact with each other. We aimed to evaluate patterns of plasma fatty acids during pregnancy and their associations with growth, body composition, and cardiometabolic health of the 6-year-old offspring. This study was performed in 4830 mother-child pairs participating in a population-based cohort in the Netherlands. Around 20 weeks of gestation, we measured plasma phospholipid concentrations of 22 fatty acids, in which we identified three fatty acid patterns using principal component analysis: a 'high n-6 polyunsaturated fatty acid (PUFA)' pattern, a 'monounsaturated and saturated fatty acid (MUFA and SFA)' pattern, and a 'high n-3 PUFA' pattern. When the children were 6 years old, we measured their anthropometrics and detailed body composition (using dual-energy X-ray absorptiometry), and we calculated their body mass index (BMI), fat mass index (FMI), fat-free mass index (FFMI). At the same age, children's blood pressure, and serum insulin, HDL-cholesterol, and triacylglycerol were measured. After adjustment for confounders and the other patterns, a higher score for the 'high n-6 PUFA' pattern during pregnancy was associated with a higher height, BMI, and FFMI in the offspring at 6 years, but not independently with cardiometabolic outcomes. The 'MUFA and SFA' pattern was not consistently associated with child body composition or cardiometabolic health. A higher score for the 'high n-3 PUFA' pattern was associated with a lower FMI, higher FFMI, higher HDL-cholesterol, and lower triacylglycerol. Our results suggest that plasma fatty acid patterns during pregnancy may affect offspring's body composition and cardiometabolic health. Specifically, a pattern characterized by high n-3 PUFA levels was associated with a more favorable body composition and blood lipid profile.

The effects of dietary macronutrients on flight ability, energetics, and fuel metabolism of yellow‐rumped warblers Setophaga coronata

The catabolism of protein from organs and muscles during migratory flight is necessary to produce glucose, key metabolic intermediates, and water, but may have negative effects on flight range and refueling at stopovers. We tested the hypothesis, suggested by previous studies, that birds that eat high‐protein insect diets use more protein for fuel in flight than those that eat high‐carbohydrate fruits. First, we fed migratory yellow‐rumped warblers synthetic fruit or mixed insect/fruit diets, and measured metabolic rates and fuel mixture under basal conditions and during exercise in a hop/hover wheel respirometer. Birds eating the fruit diet had greater plasma triglyceride and non‐esterified fatty acid concentrations, and the higher protein mixed diet increased plasma uric acid only during feeding. Diet did not affect metabolic rates or the fuel mixture under resting or exercise conditions. We then fed yellow‐rumped warblers synthetic diets that differed only in the relative proportion of carbohydrate and protein (60:15 versus 15:60 as % dry mass) and tested them in wind tunnel flights lasting up to six hours. Birds fed the high carbohydrate diet became heavier and fatter than when fed the high protein diet. Plasma uric acid concentration was increased and plasma phospholipid concentration was decreased by the high protein diet in the pre‐flight state (after a 3 h fast), but diet only affected plasma phospholipids during flight (lower in high protein birds). Neither diet nor amount of body fat affected the rate of loss of lean mass or fat during flight. Inter‐individual or seasonal differences in diet do not appear to influence the amount of protein catabolized during endurance flight. However, birds fed the high carbohydrate diet had greater voluntary flight duration, independent of body fatness, suggesting that there may be other performance benefits of high carbohydrate diets for migratory birds.

Combination of aspirin with essential fatty acids is superior to aspirin alone to prevent or ameliorate sepsis or ARDS.

It has been suggested that aspirin may be of benefit in treating sepsis and ARDS in view of its ability to block cyclo-oxygenase-1 (COX-1) and COX-2 activities; inhibit nuclear factor kappa B (NF-κB); enhance the production of endothelial nitric oxide (eNO) and lipoxin A4 (LXA4). Our previous studies revealed that plasma phospholipid content of arachidonic acid (AA) and eicosapentaenoic acid (EPA) is low in patients with sepsis. This implies that beneficial actions of aspirin in sepsis and ARDS is unlikely to be obtained in view of deficiency of AA and EPA, the precursors of LXA4 and resolvins respectively that are potent anti-inflammatory compounds and enhancers of eNO generation. In view of this, I propose that a combination of aspirin and AA and EPA (and possibly, docosahexaenoic acid, DHA) is likely to be superior in the management of sepsis and ARDS compared to aspirin alone. This suggestion is supported by the recent observation that trauma patients with uncomplicated recoveries had higher resolvin pathway gene expression and lower gene expression ratios of leukotriene: resolvin pathways.

Regulation of glucose and lipid metabolism by dietary carbohydrate levels and lipid sources in gilthead sea bream juveniles.

The long-term effects on growth performance, body composition, plasma metabolites, liver and intestine glucose and lipid metabolism were assessed in gilthead sea bream juveniles fed diets without carbohydrates (CH-) or carbohydrate-enriched (20 % gelatinised starch, CH+) combined with two lipid sources (fish oil; or vegetable oil (VO)). No differences in growth performance among treatments were observed. Carbohydrate intake was associated with increased hepatic transcripts of glucokinase but not of 6-phosphofructokinase. Expression of phosphoenolpyruvate carboxykinase was down-regulated by carbohydrate intake, whereas, unexpectedly, glucose 6-phosphatase was up-regulated. Lipogenic enzyme activities (glucose-6-phosphate dehydrogenase, malic enzyme, fatty acid synthase) and ∆6 fatty acyl desaturase (FADS2) transcripts were increased in liver of fish fed CH+ diets, supporting an enhanced potential for lipogenesis and long-chain PUFA (LC-PUFA) biosynthesis. Despite the lower hepatic cholesterol content in CH+ groups, no influence on the expression of genes related to cholesterol efflux (ATP-binding cassette G5) and biosynthesis (lanosterol 14 α-demethylase, cytochrome P450 51 cytochrome P450 51 (CYP51A1); 7-dehydrocholesterol reductase) was recorded at the hepatic level. At the intestinal level, however, induction of CYP51A1 transcripts by carbohydrate intake was recorded. Dietary VO led to decreased plasma phospholipid and cholesterol concentrations but not on the transcripts of proteins involved in phospholipid biosynthesis (glycerol-3-phosphate acyltransferase) and cholesterol metabolism at intestinal and hepatic levels. Hepatic and muscular fatty acid profiles reflected that of diets, despite the up-regulation of FADS2 transcripts. Overall, this study demonstrated that dietary carbohydrates mainly affected carbohydrate metabolism, lipogenesis and LC-PUFA biosynthesis, whereas effects of dietary lipid source were mostly related with tissue fatty acid composition, plasma phospholipid and cholesterol concentrations, and LC-PUFA biosynthesis regulation. Interactions between dietary macronutrients induced modifications in tissue lipid and glycogen content.