Remodeling of lipid landscape in high fat fed very-long chain acyl-CoA dehydrogenase null mice favors pro-arrhythmic polyunsaturated fatty acids and their downstream metabolites.

Very-long chain acyl-CoA dehydrogenase (VLCAD) catalyzes the initial step of mitochondrial long chain (LC) fatty acid ß-oxidation (FAO). Inherited VLCAD deficiency (VLCADD) predisposes to neonatal arrhythmias whose pathophysiology is still not understood. We hypothesized that VLCADD results in global disruption of cardiac complex lipid homeostasis, which may set conditions predisposing to arrhythmia. To test this, we assessed the cardiac lipidome and related molecular markers in seven-month-old VLCAD-/- mice, which mimic to some extent the human cardiac phenotype. Mice were sacrificed in the fed or fasted state after receiving for two weeks a chow or a high-fat diet (HFD), the latter condition being known to worsen symptoms in human VLCADD. Compared to their littermate counterparts, HFD/fasted VLCAD-/- mouse hearts displayed the following lipid alterations: (1) Lower LC, but higher VLC-acylcarnitines accumulation, (2) higher levels of arachidonic acid (AA) and lower docosahexaenoic acid (DHA) contents in glycerophospholipids (GPLs), as well as (3) corresponding changes in pro-arrhythmogenic AA-derived isoprostanes and thromboxane B2 (higher), and anti-arrythmogenic DHA-derived neuroprostanes (lower). These changes were associated with remodeling in the expression of gene or protein markers of (1) GPLs remodeling: higher calcium-dependent phospholipase A2 and lysophosphatidylcholine-acyltransferase 2, (2) calcium handling perturbations, and (3) endoplasmic reticulum stress. Altogether, these results highlight global lipid dyshomeostasis beyond FAO in VLCAD-/- mouse hearts, which may set conditions predisposing the hearts to calcium mishandling and endoplasmic reticulum stress and thereby may contribute to the pathogenesis of arrhythmias in VLCADD in mice as well as in humans.

Docosahexaenoic acid-rich algae oil supplementation in mothers of preterm infants is associated with a modification in breast milk oxylipins profile.

Oxylipins are derived from enzymatic and non-enzymatic oxidation of n-3 and n-6 long-chain polyunsaturated fatty acids. They are known to be involved in inflammatory processes. The aim of this study was to describe the breast milk oxylipin profile following a docosahexaenoic acid (DHA) supplementation of mothers of preterm infants. We examined the oxylipins profile in breast milk collected at day 14 post-delivery, of 40 mothers who delivered before 29 weeks of gestation and who were supplemented with either DHA-rich algae oil (S-DHA) or a placebo (PL). These mothers were selected from the MOBYDIck cohort (NCT02371460 registered on 25/05/2015 in ClinicalTrials.gov) according to the supplementation received (S-DHA vs. PL) and the DHA content quartiles as measured in breast milk (Low vs. High) to generate four study groups. Milk oxylipins, as ng/mL of milk, were analyzed by LC-MS/MS. Ten oxylipins derived from DHA were higher in the S-DHA-High group than the other three groups (P < 0.001). The 18-HEPE, was also higher in the S-DHA-High group (0.11 ± 0.01) compared to the other groups (P = 0.0001). Compared to the PL-Low group, there was a reduction in pro-inflammatory prostaglandins found in the S-DHA-High group with lower levels of prostaglandins PGF2α (0.21 ± 0.45 in the S-DHA-High group vs. 1.87 ± 0.44 in the PL-Low group, P = 0.03) and of PGE2 (0.33 ± 0.26 in the S-DHA-High group vs. 1.28 ± 0.25 in the PL-Low group, P = 0.04).In sum, the DHA supplementation was linked with a predominance of anti-inflammatory oxylipins in breast milk of mothers who delivered very preterm, like 17(S)-HDHA and 18-HEPE, precursors of D and E resolvins respectively. This was also accompanied with a lower level of pro-inflammatory prostaglandins.

Industrial and Ruminant Trans-Fatty Acids-Enriched Diets Differentially Modulate the Microbiome and Fecal Metabolites in C57BL/6 Mice.

Industrially originated trans-fatty acids (I-tFAs), such as elaidic acid (EA), and ruminant trans-fatty acids (R-tFAs), such as trans-palmitoleic acid (TPA), may have opposite effects on metabolic health. The objective was to compare the effects of consuming 2-3% I-tFA or R-tFA on the gut microbiome and fecal metabolite profile in mice after 7 and 28 days. Forty C57BL/6 mice were assigned to one of the four prepared formulations: lecithin nanovesicles, lecithin nanovesicles with EA or TPA, or water. Fecal samples and animals' weights were collected on days 0, 7, and 28. Fecal samples were used to determine gut microbiome profiles by 16S rRNA sequencing and metabolite concentrations by GC/MS. At 28 days, TPA intake decreased the abundance of Staphylococcus sp55 but increased Staphylococcus sp119. EA intake also increased the abundance of Staphylococcus sp119 but decreased Ruminococcaceae UCG-014, Lachnospiraceae, and Clostridium sensu stricto 1 at 28 days. Fecal short-chain fatty acids were increased after TPA while decreased after EA after 7 and 28 days. This study shows that TPA and EA modify the abundance of specific microbial taxa and fecal metabolite profiles in distinct ways.

Marginal Impact of Brown Seaweed Ascophyllum nodosum and Fucus vesiculosus Extract on Metabolic and Inflammatory Response in Overweight and Obese Prediabetic Subjects.

The objective of the present study was to test whether a brown seaweed extract rich in polyphenols combined with a low-calorie diet would induce additional weight loss and improve blood glucose homeostasis in association with a metabolic and inflammatory response in overweight/obese prediabetic subjects. Fifty-six overweight/obese, dysglycemic, and insulin-resistant men and women completed a randomized, placebo-controlled, double-blind, and parallel clinical trial. Subjects were administrated 500 mg/d of either brown seaweed extract or placebo combined with individualized nutritional advice for moderate weight loss over a period of 12 weeks. Glycemic, anthropometric, blood pressure, heart rate, body composition, lipid profile, gut integrity, and oxidative and inflammatory markers were measured before and at the end of the trial. No effect was observed on blood glucose. We observed significant but small decreases in plasma C-peptide at 120 min during 2 h-OGTT (3218 ± 181 at pre-intervention vs. 2865 ± 186 pmol/L at post-intervention in the brown seaweed group; 3004 ± 199 at pre-intervention vs. 2954 ± 179 pmol/L at post-intervention in the placebo group; changes between the two groups, p = 0.002), heart rate (72 ± 10 at pre-intervention vs. 69 ± 9 (n/min) at post-intervention in the brown seaweed group; 68 ± 9 at pre-intervention vs. 68 ± 8 (n/min) at post-intervention in the placebo group; changes between the two groups, p = 0.01), and an inhibition in the increase of pro-inflammatory interleukin-6 (IL-6) (1.3 ± 0.7 at pre-intervention vs. 1.5 ± 0.7 pg/L at post-intervention in the brown seaweed group; 1.4 ± 1.1 at pre-intervention vs. 2.2 ± 1.6 pg/L at post-intervention in the placebo group; changes between the two groups, p = 0.02) following brown seaweed consumption compared with placebo in the context of moderate weight loss. Although consumption of brown seaweed extract had no effect on body weight or blood glucose, an early attenuation of the inflammatory response was observed in association with marginal changes in metabolic parameters related to the prevention of diabetes type 2.

Docosahexaenoic acid-rich algae oil supplementation on breast milk fatty acid profile of mothers who delivered prematurely: a randomized clinical trial.

Preterm infants are deficient in long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), a fatty acid (FA) associated with an increase in bronchopulmonary dysplasia (BPD). In two previous randomized control trials, DHA supplementation did not reduce the risk of BPD. We examined the breast milk FA profile, collected 14 days after birth, of mothers who delivered before 29 weeks of gestation and who were supplemented with DHA-rich algae oil or a placebo within 72 h after birth as part of the MOBYDIck trial. Milk FA were analyzed by gas chromatography. The total amount of FA (mg/mL) was similar in both groups but the supplementation increased DHA (expressed as % of total FA, mean ± SD, treatment vs placebo, 0.95 ± 0.44% vs 0.34 ± 0.20%; P < 0.0001), n-6 docosapentaenoic acid (DPA) (0.275 ± 0.14% vs 0.04 ± 0.04%; P < 0.0001) and eicosapentaenoic acid (0.08 ± 0.08% vs 0.07 ± 0.07%; P < 0.0001) while decreasing n-3 DPA (0.16 ± 0.05% vs 0.17 ± 0.06%; P < 0.05). Supplementation changed the ratio of DHA to arachidonic acid (1.76 ± 1.55% vs 0.60 ± 0.31%; P < 0.0001) and n-6 to n-3 FA (0.21 ± 0.06% vs 0.17 ± 0.04%; P < 0.0001). DHA-rich algae supplementation successfully increased the DHA content of breast milk but also included secondary changes that are closely involved with inflammation and may contribute to changing clinical outcomes.

Resolvin-D2 targets myogenic cells and improves muscle regeneration in Duchenne muscular dystrophy.

Lack of dystrophin causes muscle degeneration, which is exacerbated by chronic inflammation and reduced regenerative capacity of muscle stem cells in Duchenne Muscular Dystrophy (DMD). To date, glucocorticoids remain the gold standard for the treatment of DMD. These drugs are able to slow down the progression of the disease and increase lifespan by dampening the chronic and excessive inflammatory process; however, they also have numerous harmful side effects that hamper their therapeutic potential. Here, we investigated Resolvin-D2 as a new therapeutic alternative having the potential to target multiple key features contributing to the disease progression. Our in vitro findings showed that Resolvin-D2 promotes the switch of macrophages toward their anti-inflammatory phenotype and increases their secretion of pro-myogenic factors. Moreover, Resolvin-D2 directly targets myogenic cells and promotes their differentiation and the expansion of the pool of myogenic progenitor cells leading to increased myogenesis. These effects are ablated when the receptor Gpr18 is knocked-out, knocked-down, or blocked by the pharmacological antagonist O-1918. Using different mouse models of DMD, we showed that Resolvin-D2 targets both inflammation and myogenesis leading to enhanced muscle function compared to glucocorticoids. Overall, this preclinical study has identified a new therapeutic approach that is more potent than the gold-standard treatment for DMD.

The plasma antioxidant vitamin status of the INTAPP cohort examined: The unsuspected importance of ß-carotene and γ-tocopherol in preeclampsia.

OBJECTIVE: Examine the levels of plasma antioxidant vitamins before and during a treatment with placebo or vitamin E + C supplement to prevent preeclampsia (PE). STUDY DESIGN: Per-protocol analysis of a subset group of pregnant women (n = 295) from the International Trial of Antioxidants for the Prevention of PE (INTAPP) randomized case-control study. Normotensive receiving placebo or vitamins (n = 115 and 87 respectively) were compared to gestational hypertension (GH) without proteinuria (n = 30 and 27) and PE (n = 21 and 15). Vitamin quantification was performed at 12-18, 24-26 and 32-34 weeks of gestation. MAIN OUTCOME MEASURES: Coenzyme (Co) Q10, ß-carotene and vitamins E (α and γ forms) plasma levels. RESULTS: Vitamin E + C supplementation was found to increase the α-tocopherol levels by 40% but was associated with a 57% decrease in the γ-tocopherol isoform for all study groups (p < 0.001). The ß -carotene was lower in the PE than in the normotensive and GH groups (p < 0.001) while the level of CoQ10 remained unaffected. CONCLUSIONS: A more personalized approach that target the suboptimal levels of specific antioxidants without disturbing the α/γ-tocopherol ratio could be a more successful approach to counteract oxidative stress in PE.

Impact of Dairy Intake on Plasma F2-IsoProstane Profiles in Overweight Subjects with Hyperinsulinemia: A Randomized Crossover Trial.

F2-IsoProstanes (F2-IsoPs) are major biomarkers of oxidative stress and are associated with type 2 diabetes (T2D). Further, plasma levels of F2-IsoPs may be modified by dairy products. The aim is to investigate the effect of high dairy product (HD) consumption compared to an adequate dairy product (AD) consumption on the level of F2-IsoPs among hyperinsulinemic subjects. In this crossover study, participants were randomized in two groups: HD (≥4 servings/day), or AD (≤2 servings/day) for six weeks. Fasting blood glucose and insulin were measured. The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. Six isomers of F2-IsoPs were quantified by HPLC-MS/MS. Twenty-seven subjects with hyperinsulinemia (mean age; 55 ± 13 years, BMI; 31.4 ± 3.3 kg/m2) were included. Fasting glucose, insulin and HOMA-IR were unchanged after HD or AD intervention. After HD intake, the total level of F2-IsoPs (p = 0.03), 5-F2t-IsoP (p = 0.002), and 8-F2t-IsoP (p = 0.004) decreased compared to AD. The 15-F2t-IsoP tended to be positively correlated with fasting blood glucose (r = 0.39, p = 0.08). Generally, F2-IsoPs levels were higher among men compared to women regardless of the dairy intake. Overall, intake of HD decreased plasma levels of F2-IsoPs compared to AD without modifying glycemic parameters.

High-dose vitamin-C induced prolonged factitious hyperglycemia in a peritoneal dialysis patient: a case report.

BACKGROUND: High-dose vitamin C is increasingly used for sepsis and more recently for coronavirus disease 2019 (COVID-19) infections. Proponents argue that the low cost and near perfect safety profile of vitamin C support its early adoption. Yet, adverse events might be underreported and underappreciated. CASE PRESENTATION: We report a 73-year-old non-diabetic white man with end-stage renal disease on peritoneal dialysis admitted to the intensive care unit with septic shock that was suspected to be due to peritonitis. The patient was enrolled in LOVIT (Lessening Organ Dysfunction with VITamin C; ClinicalTrials.gov identifier: NCT03680274), a randomized placebo-controlled trial of high-dose intravenous vitamin C. He developed factitious hyperglycemia, as measured with a point-of-care glucometer, that persisted for 6 days after discontinuation of the study drug, confirmed to be vitamin C after unblinding. He also had short-lived iatrogenic coma because of hypoglycemia secondary to insulin administration. These events triggered a protocol amendment. CONCLUSIONS: Although factitious hyperglycemia has been reported before using certain glucometers in patients treated with high-dose vitamin C, the persistence of this phenomenon for 6 days after the discontinuation of the therapy is a distinguishing feature. This case highlights the importance of monitoring glucose with a core laboratory assay for up to a week in specific populations, such as patients on peritoneal dialysis.

Maternal vitamin D, oxidative stress, and pre-eclampsia.

OBJECTIVE: To examine the associations between risk of pre-eclampsia and pregnancy levels of maternal 25-hydroxyvitamin D (25[OH]D) and oxidative stress biomarkers. METHODS: A nested case-control study (n = 99; 34 cases; 65 controls) within a prospective pregnancy cohort. Maternal 25(OH)D and oxidative stress markers (six isomers of F2 -isoprostanes; F2 -isoPs) were measured in plasma at 12-18 and 24-26 gestational weeks. Vitamin D deficiency was defined as 25[OH]D less than 50 nmol/L. RESULTS: Maternal vitamin D deficiency was associated with increased 8-iso-PGF2α (P = 0.037), 15(R)-PGF2α (P = 0.004), (±)5-iPF2α -VI (P = 0.026) at 12-18 weeks. Vitamin D deficiency was inversely associated with 8-iso-PGF2α (P = 0.019) and (±)5-iPF2α -VI isomer (P = 0.010) at 24-26 weeks. Both maternal vitamin D deficiency (adjusted odds ratio [aOR], 4.79; 95% confidence interval [CI], 1.67-13.75) and increased (±)5-iPF2α -VI (aOR, 2.46; 95% CI, 1.16-5.22) at 24-26 weeks were associated with risk of pre-eclampsia. However, the interaction test between 25(OH)D and (±)5-iPF2α -VI was not significant (P = 0.143). CONCLUSION: Plasma 25(OH)D below 50 nmol/L was associated with increased oxidative stress levels during pregnancy as measured by two F2 -isoP isomers, including the well-studied marker 8-iso-PGF2α . Whether vitamin D-induced oxidative stress mediates the risk of pre-eclampsia warrants future study.

Long chain omega-3 fatty acids and their oxidized metabolites are associated with reduced prostate tumor growth.

INTRODUCTION: Cancer has been associated with increased oxidative stress and deregulation of bioactive oxylipins derived from long-chain polyunsaturated fatty acids (LC-PUFA) like arachidonic acid (AA). There is a debate whether ω-3 LC-PUFA could promote or prevent prostate tumor growth through immune modulation and reduction of oxidative stress. Our aim was to study the association between enzymatically or non-enzymatically produced oxidized-LC-PUFA metabolites and tumor growth in an immune-competent eugonadal and castrated C57BL/6 male mice injected with TRAMP-C2 prostate tumor cells, fed with ω-3 or ω-6 LC-PUFA-rich diets. MATERIALS AND METHODS: Tumor fatty acids were profiled by gas chromatography and 26 metabolites derived from either AA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were assessed by liquid chromatography-mass spectrometry. RESULTS: The enriched ω-3 diet did not reduce oxidative stress overall in tumors but favored the formation of ω-3 rather than ω-6 derived isoprostanoids. We discovered that EPA and its oxidized-derivatives like F3-isoprostanes and prostaglandin (PG)F3α, were inversely correlated with tumor volume (spearman correlations and T-test, p<0.05). In contrast, F2-isoprostanes, adrenic acid, docosapentaenoic acid (DPAω-6) and PGE2 were positively correlated with tumor volume. Interestingly, F4-neuroprostanes, PGD2, PGF2α, and thromboxane were specifically increased in TRAMP-C2 tumors of castrated mice compared to those of eugonadal mice. DISCUSSION: Decreasing tumor growth under ω-3 diet could be attributed in part to increased levels of EPA and its oxidized-derivatives, a reduced level of pro-angiogenic PGE2 and increased levels of F4-neuroprostanes and resolvins content in tumors, suspected of having anti-proliferative and anti-inflammatory effects.

Statistical and Machine-Learning Analyses in Nutritional Genomics Studies.

Nutritional compounds may have an influence on different OMICs levels, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, and metagenomics. The integration of OMICs data is challenging but may provide new knowledge to explain the mechanisms involved in the metabolism of nutrients and diseases. Traditional statistical analyses play an important role in description and data association; however, these statistical procedures are not sufficiently enough powered to interpret the large integrated multiple OMICs (multi-OMICS) datasets. Machine learning (ML) approaches can play a major role in the interpretation of multi-OMICS in nutrition research. Specifically, ML can be used for data mining, sample clustering, and classification to produce predictive models and algorithms for integration of multi-OMICs in response to dietary intake. The objective of this review was to investigate the strategies used for the analysis of multi-OMICs data in nutrition studies. Sixteen recent studies aimed to understand the association between dietary intake and multi-OMICs data are summarized. Multivariate analysis in multi-OMICs nutrition studies is used more commonly for analyses. Overall, as nutrition research incorporated multi-OMICs data, the use of novel approaches of analysis such as ML needs to complement the traditional statistical analyses to fully explain the impact of nutrition on health and disease.

Increased Dairy Product Intake Alters Serum Metabolite Profiles in Subjects at Risk of Developing Type 2 Diabetes.

SCOPE: Metabolomics is increasingly used to identify biomarkers of diet or chronic diseases, such as type 2 diabetes. Yet, metabolite signatures following dairy intake in hyperinsulinemic subjects have not been identified. The objective is to evaluate the effects of a high dairy diet (HD) for 6 weeks (4 servings or more per day), compared with an adequate dairy diet (AD) (2 servings or less per day), on serum metabolite profiles in hyperinsulinemic adults. METHODS AND RESULTS: In this crossover trial, subjects are randomized to HD or AD for 6 weeks. Serum metabolites are assessed using GC/MS. Twenty-six subjects completed the study. Levels of pentadecanoic acid, tyrosine and lathosterol are increased in HD, while 1,5-anhydrosorbitol, myo-inositol, 3-aminoisobutyric acid and beta-sitosterol are decreased (p < 0.05). Sorbitol levels are increased after AD, while hexanoic acid, lauric acid, l-kynurenine, methionine, and benzoic acid levels are reduced (p < 0.05). Histidine, caprylic acid, nonanoic acid, decanoic acid, lauric acid, heptadecanoic acid, and benzoic acid levels are increased in HD compared to AD, while malic acid levels are increased in AD compared with HD (p < 0.05). CONCLUSION: Higher dairy products intake modifies metabolite profiles in hyperinsulinemic subjects.

Physical fitness is associated with prostaglandin F2α isomers during pregnancy.

INTRODUCTION: Pregnancy and physical activity are associated with oxidative stress and immune changes. We hypothesized that pregnant women physically more active in early pregnancy will display a better oxidative stress management and inflammatory response later in pregnancy compared with less active pregnant women. MATERIAL AND METHODS: Maternal physical activity using accelerometry monitors for 1 week and cardiorespiratory fitness (VO2 at anaerobic threshold) were assessed at 14-18 weeks in 58 pregnant women. Plasma and erythrocytes membrane samples were obtained from maternal blood samples at 14-18 and 34-37 weeks of pregnancy. Pro-inflammatory prostaglandin (PG) F2α and oxidative stress-derived F2-isoprostanes were measured by high-performance liquid chromatography coupled to tandem mass spectrometry. RESULTS: Higher physical activity levels at 14-18 weeks measured by mean counts per minute, >30 min/d of moderate to vigorous activity or >6500 steps/d at 14-18 weeks of pregnancy were associated with lower levels of total plasmatic PGF2α later in pregnancy. Concentrations of 5 F2-isomers in erythrocyte membranes in late pregnancy were significantly higher in the third (17.5-19.5 mL kg-1 min-1) and/or fourth (19.6-27.7 mL kg-1 min-1) quartiles of cardio-respiratory fitness compared to the first quartile (13.9-15.9 mL kg-1 min-1). CONCLUSIONS: Overall, higher cardio-respiratory fitness in early pregnancy is associated with enhanced erythrocyte membranes oxidation at 34-37 weeks reflecting a higher oxygen transfer capacity. Also, the most active women experienced lower circulating levels of pro-inflammatory PGF2α in plasma at 34-37 weeks, a marker associated with adverse antenatal inflammation-associated conditions. These results support the practice of physical activity by pregnant women.

F2-isoprostanes and fatty acids profile in early pregnancy complicated by pre-existing diabetes.

BACKGROUND: Diabetes and pregnancy are both associated with oxidative stress, characterized by an increase of F2-isoprostanes from the non-enzymatic oxidation of arachidonic acid, a n - 6 polyunsaturated fatty acid (PUFA). We hypothesized that pregnant women with pre-existing diabetes will be characterized by elevated levels of specific F2-isoPs isomers and altered PUFA composition in plasma early pregnancy when compared to normoglycemic controls. METHODS: Plasma samples from 23 women with uncomplicated pregnancies and 11 women with pre-existing diabetes in pregnancy were collected between 12 and 18 weeks of pregnancy (MIROS cohort). Six F2-isoprostanes isomers were measured by high-performance liquid chromatography coupled to tandem mass spectrometry. Fatty acids concentrations in plasmatic phospholipids were measured by gas chromatography coupled to a flame ionization detector. RESULTS: F2-isoprostanes, specifically the 8-iso-15(R)-PGF2α levels, were 67% higher in diabetic than normoglycemic pregnancies (p = 0.026). The total n - 6 PUFA and arachidonic acid level did not differ between study groups. In contrast, total n - 3 level was 32% lower in diabetic pregnancies than in controls (p = 0.002); EPA(20:5) and DHA(22:6) being specifically reduced (p = 0.035 and p = 0.003 respectively). Delta-6-desaturase (D6D) activity index, calculated using fatty acid ratios, was 9% lower in pre-existing diabetes than in controls (p = 0.042). CONCLUSIONS: Pre-existing diabetes in early pregnancy displays a distinctive F2-isoprostanes profile when compared to other pathologies of pregnancy, such as preeclampsia, as previously assessed in the same cohort.

Modulation of the biomarkers of inflammation and oxidative stress by ruminant trans fatty acids and dairy proteins in vascular endothelial cells (HUVEC).

This study aimed to determine whether dairy macronutrients alter markers of inflammation and oxidative stress in endothelial cells. Human endothelial cells (HUVEC) were treated with ruminant trans fatty acids (rTFA), either trans-vaccenic acid (tVA) or trans-palmitoleic acid (tPA), whey protein hydrolysate, leucine or combinations of rTFA and dairy protein compounds. Industrial TFA elaidic acid (EA) was also investigated and compared with rTFA. Inflammatory prostaglandins (PG) and F2-isoprostanes (F2-isoP) isomers, markers of oxidative stress, were assessed in cell supernatants by LC-MS/MS. Both tVA and tPA, as well as whey protein hydrolysate, decreased TNFα-induced PG excretion. Combinations of rTFA and dairy protein compounds decreased inflammation to a similar extent than rTFA alone. EA increased class VI F2-isoP isomers, whereas tVA mostly raised class III isomers. In summary, rTFA decreased inflammatory markers and increased oxidative stress markers in endothelial cells. Combinations of rTFA with whey proteins or leucine showed no additive effect.

Alterations of fatty acid profiles in gestational diabetes and influence of the diet.

Gestational diabetes mellitus (GDM) is a pregnancy-induced complication with increased prevalence, especially in overweight women. Fatty acid (FA) composition in tissues can reflect dietary fat intake, especially essential FA intake. Moreover, it has been shown that FA profiles in blood lipid fractions are altered in diabetic patients. Consequently, women with GDM may also have a distinctive FA profile. The objective of this review is compare FA profiles in different blood lipid fractions and the influence of dietary fat intake in women with GDM or normoglycemic pregnancies. Results show that women with GDM have more saturated and less polyunsaturated FA (PUFA) in their red blood cell (RBC) membranes than normoglycemic pregnant women. Moreover, some studies reported that women with GDM have a greater energy intake from total fat and saturated FA, along with a lower energy intake from PUFA, when compared to normoglycemic pregnancies. Clinical trials showed that omega-3 PUFA levels in RBC membranes of GDM women can be restored by a dietary intervention. Further research is required to determine whether FA profiles are altered prior to the diagnosis of GDM and can be prevented by diet.

Trans Fatty Acids Suppress TNF-α-Induced Inflammatory Gene Expression in Endothelial (HUVEC) and Hepatocellular Carcinoma (HepG2) Cells.

Trans fatty acids (TFA) intake has been linked to cardiovascular diseases and liver diseases; yet the effect of TFA on inflammation remains controversial. Accordingly, the objective of this paper was to determine the in vitro effects of TFA on inflammatory gene expression. Human umbilical vein endothelial cells (HUVEC) and human hepatocellular carcinoma (HepG2) cells were treated for 24 h with either trans-vaccenic acid (tVA), trans-palmitoleic acid (tPA) or elaidic acid (EA) at concentrations of 5-150 µM, or with a mixture of tVA and tPA (150/50 µM). All TFA were highly incorporated into cell membranes, as determined by gas chromatography, representing 15-20% of total fatty acids in HUVEC and 3-8% in HepG2 cells. Incorporation of EA, a common industrial TFA, increased the ratio of the stearoyl-CoA desaturase (SCD-1), a key enzyme involved in fatty acid metabolism. Ruminant TFA, including tVA, tPA and the mixture of tVA and tPA, significantly reduced the TNF-α-induced gene expression of TNF, VCAM-1 and SOD2 in HUVEC, as well as TNF and IL-8 in HepG2 cells. EA also decreased inflammatory gene expression in HUVEC, but not in HepG2 cells. The inhibition of peroxisome proliferator-activated receptor (PPAR)-γ did not influence the effects of TFA on gene expression. Overall, physiological and supraphysiological concentrations of TFA, especially tVA and tPA, prevented inflammatory gene expression in vitro. This effect is independent of PPAR-γ activation and may be due to an alteration of fatty acid metabolism in cell membranes caused by the high incorporation of TFA.

Thermal conductivity of the sideledge in aluminium electrolysis cells: Experiments and numerical modelling.

During aluminium electrolysis, a ledge of frozen electrolytes is generally formed, attached to the sides of the cells. This ledge acts as a protective layer, preventing erosion and chemical attacks of both the electrolyte melt and the liquid aluminium on the side wall materials. The control of the sideledge thickness is thus essential in ensuring a reasonable lifetime for the cells. The key property for modelling and predicting the sideledge thickness as a function of temperature and electrolyte composition is the thermal conductivity. Unfortunately, almost no data is available on the thermal conductivity of the sideledge. The aim of this work is to alleviate this lack of data. For seven different samples of sideledge microstructures, recovered from post-mortem industrial electrolysis cells, the thermal diffusivity, the density, and the phase compositions were measured in the temperature range of 423 K to 873 K. The thermal diffusivity was measured with a laser flash technique and the average phase compositions by X-ray diffraction analysis. The thermal conductivity of the sideledge is deduced from the present experimental thermal diffusivity and density, and the thermodynamically assessed heat capacity. In addition to the present experimental work, a theoretical model for the prediction of the effective thermal transport properties of the sideledge microstructure is also proposed. The proposed model considers an equivalent microstructure and depends on phase fractions, porosity, and temperature. The strength of the model lies in the fact that only a few key physical properties are required for its parametrization and they can be predicted with a good accuracy via first principles calculations. It is shown that the theoretical predictions are in a good agreement with the present experimental measurements.

Experimental Determination of the Thermal Diffusivity of α-Cryolite up to 810 K and Comparison with First Principles Predictions.

In aluminum electrolysis cells, a ledge of frozen electrolyte is formed on the sides. Controlling the side ledge thickness (a few centimeters) is essential to maintain a reasonable life span of the electrolysis cell, as the ledge acts as a protective layer against chemical attacks from the electrolyte bath used to dissolve alumina. The numerical modeling of the side ledge thickness, by using, for example, finite element analysis, requires some input data on the thermal transport properties of the side ledge. Unfortunately, there is a severe lack of experimental data, in particular, for the main constituent of the side ledge, the cryolite (Na3AlF6). The aim of this study is twofold. First, the thermal transport properties of cryolite, not available in the literature, were measured experimentally. Second, the experimental data were compared with previous theoretical predictions based on first principle calculations. This was carried out to evaluate the capability of first principle methods in predicting the thermal transport properties of complex insulating materials. The thermal diffusivity of a porous synthetic cryolite sample containing 0.9 wt % of alumina was measured over a wide range of temperature (473-810 K), using the monotone heating method. Because of limited computational resources, the first principle method can be used only to determine the thermal properties of single crystals. The dependence of thermal diffusivity of the Na3AlF6 + 0.9 wt % Al2O3 mixture on the microstructural parameters is discussed. A simple analytical function describing both thermal diffusivity and thermal conductivity of cryolite as a function of temperature is proposed.