Models predict change in plasma triglyceride concentrations and long-chain n-3 polyunsaturated fatty acid proportions in healthy participants after fish oil intervention.

Introduction: Substantial response heterogeneity is commonly seen in dietary intervention trials. In larger datasets, this variability can be exploited to identify predictors, for example genetic and/or phenotypic baseline characteristics, associated with response in an outcome of interest. Objective: Using data from a placebo-controlled crossover study (the FINGEN study), supplementing with two doses of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs), the primary goal of this analysis was to develop models to predict change in concentrations of plasma triglycerides (TG), and in the plasma phosphatidylcholine (PC) LC n-3 PUFAs eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA), after fish oil (FO) supplementation. A secondary goal was to establish if clustering of data prior to FO supplementation would lead to identification of groups of participants who responded differentially. Methods: To generate models for the outcomes of interest, variable selection methods (forward and backward stepwise selection, LASSO and the Boruta algorithm) were applied to identify suitable predictors. The final model was chosen based on the lowest validation set root mean squared error (RMSE) after applying each method across multiple imputed datasets. Unsupervised clustering of data prior to FO supplementation was implemented using k-medoids and hierarchical clustering, with cluster membership compared with changes in plasma TG and plasma PC EPA + DHA. Results: Models for predicting response showed a greater TG-lowering after 1.8 g/day EPA + DHA with lower pre-intervention levels of plasma insulin, LDL cholesterol, C20:3n-6 and saturated fat consumption, but higher pre-intervention levels of plasma TG, and serum IL-10 and VCAM-1. Models also showed greater increases in plasma PC EPA + DHA with age and female sex. There were no statistically significant differences in PC EPA + DHA and TG responses between baseline clusters. Conclusion: Our models established new predictors of response in TG (plasma insulin, LDL cholesterol, C20:3n-6, saturated fat consumption, TG, IL-10 and VCAM-1) and in PC EPA + DHA (age and sex) upon intervention with fish oil. We demonstrate how application of statistical methods can provide new insights for precision nutrition, by predicting participants who are most likely to respond beneficially to nutritional interventions.

Randomized Trial of Ciprofloxacin Doxycycline and Hydroxychloroquine Versus Budesonide in Active Crohn's Disease.

BACKGROUND: Increased mucosa-associated E. coli are present in Crohn's disease, but their role in pathogenesis is uncertain. AIMS: To assess efficacy and safety of an antibiotic/hydroxychloroquine combination effective against E. coli inside macrophages. METHODS: Adults with moderately active disease (CDAI > 220-450 plus C reactive protein ≥ 5 mg/l and/or fecal calprotectin > 250 µg/g) were randomized to receive (open-label) oral budesonide (Entocort CR 9 mg/day 8 weeks, 6 mg/day 2 weeks, 3 mg/day 2 weeks) or oral ciprofloxacin 500 mg bd, doxycycline 100 mg bd, hydroxychloroquine 200 mg tds for 4 weeks, followed by doxycycline 100 mg bd and hydroxychloroquine 200 mg tds for 20 weeks. Primary endpoints were remission (CDAI ≤ 150) at 10 weeks, remission maintained to 24 weeks, and remission maintained to 52 weeks. Patients not responding (CDAI fall by > 70) by 10 weeks were invited to crossover onto the alternative therapy. RESULTS: Fifty-nine patients were recruited across 8 sites. Including crossover, 39 patients received antibiotics/hydroxychloroquine and 39 received budesonide. At 10 weeks, 24 weeks, and 52 weeks on initial therapy, only 2/27, 2/27, and 1/27 were in remission on antibiotics/hydroxychloroquine compared with 8/32, 1/32, and 1/32 on budesonide (P = 0.092 at 10 weeks). Withdrawals by 10 weeks due to adverse events were seen in 15 receiving antibiotics/hydroxychloroquine and 6 budesonide. Results including crossover were more promising with 9/24 patients receiving antibiotics/hydroxychloroquine per protocol in remission by 24 weeks. No correlation was seen between response to antibiotics/hydroxychloroquine and ASCA/OmpC antibody status or disease location. CONCLUSION: Overall results with this antibiotic/hydroxychloroquine combination were unimpressive, but long-term remission is seen in some patients and justifies further study.

The nutritional and cardiovascular health benefits of rapeseed oil-fed farmed salmon in humans are not decreased compared with those of traditionally farmed salmon: a randomized controlled trial.

PURPOSE: Farmed fish are increasingly raised on feeds containing vegetable oils, which affects their composition and possibly health properties. We investigated the effects of consuming farmed salmon, raised on different feeding regimes, on nutrient status and health outcomes in healthy subjects. METHODS: Salmon were grown on feeds containing mainly fish oil (FO) or rapeseed oil (RO), resulting in an eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) content of fillets of 2.1 or 0.9 g/100 g, respectively. In a randomized parallel controlled trial, 51 healthy subjects were allocated to consume 2 portions/week of FO salmon (n = 17), RO salmon (n = 17) or no additional salmon (Control, n = 17) as part of their habitual diet, for 18 weeks. We collected blood at 0, 9 and 18 weeks to measure omega-3 index (O3I) in red blood cells, plasma markers of cardiovascular risk, serum 25(OH)-vitamin D3 (25(OH)D3) and plasma trace elements. RESULTS: After 18 weeks, O3I was similarly increased in subjects consuming 2 portions/week of FO or RO salmon compared to control (both p < 0.05). Serum 25(OH)D3 was significantly higher, whereas plasma triacylglycerols were significantly lower in subjects consuming RO salmon compared to control (both p < 0.05). Heart rate was significantly lower in subjects consuming FO salmon after 9 weeks, compared to control (p < 0.01). Salmon consumption did not affect other markers. CONCLUSION: Consuming two portions/week of salmon raised on rapeseed oil rather than fish oil increased the O3I and vitamin D status, and decreased plasma triacylglycerols. These outcomes endorse opportunities for developing more sustainable feeds within aquaculture food systems. CLINICAL TRIAL REGISTRY: This trial was registered at clinicaltrials.gov as NCT01916434.

The potential impact of compositional changes in farmed fish on its health-giving properties: is it time to reconsider current dietary recommendations?

Assessment of national dietary guidelines in a number of European countries reveals that some are based on cohort studies, focusing on total seafood consumption, while others are based on the content of EPA and DHA, distinguishing between oily and other fish. The mean actual intake of fish in most countries is around or below the recommended intake, with differences in intake of fish being present between sex and age groups. Many people do not reach the national recommendation for total fish intake. Dietary recommendations for fish and EPA/DHA are based mainly on data collected more than 10 years ago. However, methods of farmed fish production have changed considerably since then. The actual content of EPA and DHA in farmed salmon has nearly halved as the traditional finite marine ingredients fish meal and fish oil in salmon diets have been replaced with sustainable alternatives of terrestrial origin. As farmed salmon is an important source of EPA and DHA in many Western countries, our intake of these fatty acids is likely to have decreased. In addition, levels of vitamin D and Se are also found to have declined in farmed fish in the past decade. Significant changes in the EPA and DHA, vitamin D and Se content of farmed fish means that average intakes of these nutrients in Western populations are probably lower than before. This may have consequences for the health-giving properties of fish as well as future dietary recommendations for fish intake.

Fish oil supplemented for 9 months does not improve glycaemic control or insulin sensitivity in subjects with impaired glucose regulation: a parallel randomised controlled trial.

The effects of fish oil (FO) supplementation on glycaemic control are unclear, and positive effects may occur only when the phospholipid content of tissue membranes exceeds 14% as n-3 PUFA. Subjects (n 36, thirty-three completed) were paired based on metabolic parameters and allocated into a parallel double-blind randomised trial with one of each pair offered daily either 6 g of FO (3·9 g n-3 PUFA) or 6 g of maize oil (MO) for 9 months. Hyperinsulinaemic-euglycaemic-euaminoacidaemic (HIEGEAA) clamps (with [6,6 2H2 glucose]) were performed at the start and end of the intervention. Endogenous glucose production (EGP) and whole-body protein turnover (WBPT) were each measured after an overnight fast. The primary outcome involved the effect of oil type on insulin sensitivity related to glycaemic control. The secondary outcome involved the effect of oil type on WBPT. Subjects on FO (n 16) had increased erythrocyte n-3 PUFA concentrations >14%, whereas subjects on MO (n 17) had unaltered n-3 PUFA concentrations at 9%. Type of oil had no effect on fasting EGP, insulin sensitivity or total glucose disposal during the HIEGEAA clamp. In contrast, under insulin-stimulated conditions, total protein disposal (P=0·007) and endogenous WBPT (P=0·001) were both increased with FO. In an associated pilot study (n 4, three completed), although n-3 PUFA in erythrocyte membranes increased to >14% with the FO supplement, the enrichment in muscle membranes remained lower (8%; P<0·001). In conclusion, long-term supplementation with FO, at amounts near the safety limits set by regulatory authorities in Europe and the USA, did not alter glycaemic control but did have an impact on WBPT.

Supplementation with a 9c,11t-rich conjugated linoleic acid blend shows no clear inhibitory effects on platelet function in healthy subjects at low and moderate cardiovascular risk: a randomized controlled trial.

SCOPE: The 9cis,11trans-conjugated linoleic acid (9c,11t-CLA) is reported to have anti-atherogenic properties in animal models and to modulate protein expression in unstimulated human platelets in vivo. Platelet function was therefore investigated after dietary supplementation with 9c,11t-CLA enriched oil (CLA80:20) in a randomized, baseline-controlled cross-over trial. METHODS AND RESULTS: Forty-three healthy adults at low to moderate risk of cardiovascular disease received 4 g/day of CLA80:20 or placebo for two weeks each. Platelet function, inflammation, and endothelial activation were assessed before and after each phase. Compared with placebo, supplementation had no significant effects on platelet function measured by Platelet Function Analyzer-100. Inhibitory effects on collagen-induced aggregation were sex-dependent (p = 0.005) that reached significance only in women (p = 0.045). Thrombin receptor-activating peptide (TRAP)-induced P-selectin expression was higher after supplementation in all subjects (p = 0.017). TRAP-induced platelet fibrinogen binding was also dependent on sex (p = 0.015), with fibrinogen binding after CLA80:20 being higher in males (p = 0.035). Plasma monocyte chemoattractant protein-1 was higher (p = 0.041) after CLA80:20. CONCLUSION: No clear evidence was found for inhibition or activation of platelet function as well as inflammation by CLA80:20 in a low to moderate cardiovascular risk group.

Postprandial cell defense system responses to meal formulations: stratification through gene expression profiling.

SCOPE: Cell defenses regulating homeostatic control of postprandial stress are influenced by interindividual variation, food composition and health status. This study investigates effects of food composition on individual postprandial responses and associations with health. METHODS AND RESULTS: Volunteers (n = 16) consumed four food formulations (50% unsaturated/saturated fat, with/without beetroot extract 10 g/100 g) on separate occasions. GeXP assay measured whole blood postprandial gene expression profiles of 28 cell defense markers at baseline and postprandial time points 1, 2, 4, 6, 24 h. Plasma markers of metabolic lipids, hormones, inflammatory cytokines, oxidative stress, and DNA damage/repair were also assessed. SIRT 1, UCP2, HO1, GSS, PTGS2, TP53, CDKN2A, PPIA, SOCS3, and APE1 expression profiles revealed distinct stratified subgroups associated with plasma HDLs, TNF-α and postprandial responses of SOCS3, and PPIA. Leptin, IL6, and DNA strand breaks revealed differing responses to fat type consumed. CONCLUSION: This study demonstrates postprandial immune, inflammatory, redox, metabolic, and DNA repair responses that are largely independent of fat type consumed (unsaturated/saturated) or addition of beetroot extract, in apparently healthy individuals. However, postprandial responses can be characterized by regulation of gene expression associated with markers linked to health status and are subject to interindividual variation that can influence postprandial responses.

Folate in pregnancy and imprinted gene and repeat element methylation in the offspring.

BACKGROUND: Epigenetic regulation of imprinted genes and transposable elements has been implicated in human disease and may be affected by maternal diet. OBJECTIVE: The objective was to determine the effect on offspring epigenetic status of nutritional and genetic factors that influence folate exposure in pregnancy. DESIGN: We measured folate intake from diet, the use of folic acid supplements and the period of consumption, maternal and cord red blood cell (RBC) folate, and genotypes for 5 methylation cycle enzymes in a prospective cohort study of pregnancies in the United Kingdom between 2000 and 2006. We related these to offspring methylation status within 3 maternally methylated imprinted genes: paternally expressed gene 3 (PEG3), insulin-like growth factor 2 (IGF2), and small nuclear ribonucleoprotein polypeptide N, and the long interspersed nuclear element 1 (LINE-1) in genomic DNA extracted from whole blood in 913 pregnancies. RESULTS: Supplement use after 12 wk of gestation was associated with a higher level of methylation in IGF2 (+0.7%; 95% CI: 0.02, 1.4; P = 0.044) and reduced methylation in both PEG3 (-0.5%; 95% CI: -0.9, -0.1; P = 0.018) and LINE-1 (-0.3%; 95% CI: -0.6, -0.04; P = 0.029). The same pattern was observed in relation to RBC folate in the cord blood at birth: IGF2 (P = 0.038), PEG3 (P < 0.001), and LINE-1 (P < 0.001). LINE-1 methylation was related to maternal RBC folate (P = 0.001) at 19 wk. No effect of supplement use up to 12 wk (current recommendation) was found. CONCLUSIONS: Folic acid use after 12 wk of gestation influences offspring repeat element and imprinted gene methylation. We need to understand the consequences of these epigenetic effects.

Vitamin D in pregnancy at high latitude in Scotland.

The aims of the present study were to determine compliance with current advice on vitamin D and to assess the influence of season, dietary intake, supplement use and deprivation on vitamin D status in pregnant mothers and newborns in the north of Scotland where sunlight exposure is low. Pregnant women (n 1205) and their singleton newborns were studied in the Aberdeen Maternity Hospital (latitude 57°N) between 2000 and 2006. Plasma 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 were measured at 19 weeks of gestation in mothers and at delivery in newborns. During pregnancy, 21·0 (95 % CI 18·5, 23·5) % of women took vitamin D supplements. The median intake was 5 µg/d and only 0·6 (95 % CI 0·1, 1·0) % took the recommended 10 µg/d. Supplement use, adjusted for season, dietary intake and deprivation, significantly increased maternal 25-hydroxyvitamin D (25(OH)D) by 10·5 (95 % CI 5·7, 15·2) nmol/l (P< 0·001); however, there was no significant effect on cord 25(OH)D (1·4 (95 % CI - 1·8, 4·5) nmol/l). The biggest influence on both maternal and cord 25(OH)D was season of birth (P< 0·001). Compared with the least deprived women (top three deciles), the most deprived pregnancies (bottom three deciles) were characterised by a significantly lower seasonally adjusted 25(OH)D ( - 11·6 (95 % CI - 7·5, - 15·7) nmol/l in the mother and - 5·8 (95 % CI - 2·3, - 9·4) nmol/l in the cord), and a lower level of supplement use (10 (95 % CI 4, 17) v. 23 (95 % CI 20, 26) %). More should be done to promote vitamin D supplement use in pregnancy but the critical importance of endogenous vitamin D synthesis, and known adaptations of fat metabolism specific to pregnancy, suggest that safe sun advice may be a useful additional strategy, even at high latitude.

Alperujo extract, hydroxytyrosol, and 3,4-dihydroxyphenylglycol are bioavailable and have antioxidant properties in vitamin E-deficient rats--a proteomics and network analysis approach.

SCOPE: Olive products are rich in phenolic compounds, which are natural antioxidants in vitro. We tested the in vivo effects of alperujo, an olive production by-product, as well as hydroxytyrosol and 3,4-dihydroxyphenylglycol (DHPG) isolated from alperujo, on indices and pathways of oxidative and metabolic stress in a vitamin E-deficient rat model. METHODS AND RESULTS: Rats were fed a vitamin E-deficient diet for 10 weeks, followed by this diet supplemented with either 100 mg/kg diet dα-tocopherol, alperujo extract, hydroxytyrosol, or 10 mg/kg diet DHPG, for a further 2 weeks. We detected alperujo phenolics in tissues and blood, indicating they are bioavailable. Alperujo extract partially ameliorated elevated plasma levels of thiobarbituric acid reactive substances and also lowered plasma cholesterol levels, whereas hydroxytyrosol increased plasma triglyceride levels. Proteomics and subsequent network analysis revealed that hepatic mitochondrial aldehyde dehydrogenase (ALDH2), of which protein and activity levels were regulated by dα-tocopherol and olive phenolics, represents a novel central regulatory protein hub affected by the dietary interventions. CONCLUSION: The in vivo free radical scavenging properties of olive phenolics appear relatively modest in our model. But alternative mechanisms, including regulation of ALDH2, may represent relevant antioxidant mechanisms by which dietary olive phenolics could have beneficial impact on cardiovascular health.

Effect of supplementation with an 80:20 cis9,trans11 conjugated linoleic acid blend on the human platelet proteome.

SCOPE: The dietary fatty acid cis9,trans11 conjugated linoleic acid (cis9,trans11 CLA) has been shown to modify the function of endothelial cells, monocytes, and platelets, all of which are involved in the development of atherosclerosis. Potential mechanisms for the platelet effects have not been assessed previously. In this study, we assessed how supplementation of the diet with an 80:20 cis9,trans11 CLA blend affects the platelet proteome. METHODS AND RESULTS: In a double-blind, randomized, placebo-controlled, parallel-group trial, 40 overweight but apparently healthy adults received either 4 g per day of cis9,trans11 CLA-enriched oil or placebo oil, consisting of palm oil and soybean oil, for 3 months. Total platelet proteins were extracted from washed platelets, separated using two-dimensional gel electrophoresis and differentially regulated protein spots were identified by LC-ESI-MS/MS. Supplementation with the CLA blend, compared with placebo, resulted in significant alterations in levels of 46 spots (p < 0.05), of which 40 were identified. Network analysis revealed that the majority of these proteins participate in regulation of the cytoskeleton and platelet structure, as well as receptor action, signaling, and focal adhesion. CONCLUSION: The platelet proteomics approach revealed novel insights into regulation of cellular biomarkers of atherogenic and thrombotic pathways by an 80:20 cis9,trans11 CLA blend.

Effect of a tomato-rich diet on markers of cardiovascular disease risk in moderately overweight, disease-free, middle-aged adults: a randomized controlled trial.

BACKGROUND: Cardiovascular disease (CVD) is a major cause of mortality in the United Kingdom. Epidemiologic studies suggest that consumption of tomato-based foods may lower CVD risk. Such potential benefits have been ascribed in part to high concentrations of lycopene in the tomatoes. However, these findings have not yet been validated by comprehensive intervention trials. OBJECTIVE: The aim of this study was to conduct a single-blind, randomized controlled intervention trial with healthy middle-aged volunteers to assess whether the consumption of tomato-based foods affects recognized biomarkers of CVD risk. DESIGN: After a 4-wk run-in period with a low-tomato diet, 225 volunteers (94 men and 131 women) aged 40-65 y were randomly assigned into 1 of 3 dietary intervention groups and asked to consume a control diet (low in tomato-based foods), a high-tomato-based diet, or a control diet supplemented with lycopene capsules (10 mg/d) for 12 wk. Blood samples were collected at baseline, at 6 wk, and after the intervention and were analyzed for carotenoid and lipid profiles and inflammatory markers. Blood pressure, weight, and arterial stiffness were also measured. Dietary intake was also determined during the intervention. RESULTS: None of the systemic markers (inflammatory markers, markers of insulin resistance and sensitivity) changed significantly after the dietary intervention. Moreover, lipid concentrations and arterial stiffness were also unaffected by the interventions. CONCLUSION: These data indicate that a relatively high daily consumption of tomato-based products (equivalent to 32-50 mg lycopene/d) or lycopene supplements (10 mg/d) is ineffective at reducing conventional CVD risk markers in moderately overweight, healthy, middle-aged individuals. This trial was registered at isrctn.org as ISRCTN34203810.

Ginger phytochemicals mitigate the obesogenic effects of a high-fat diet in mice: a proteomic and biomarker network analysis.

SCOPE: Natural dietary anti-obesogenic phytochemicals may help combat the rising global incidence of obesity. We aimed to identify key hepatic pathways targeted by anti-obsogenic ginger phytochemicals fed to mice. METHODS AND RESULTS: Weaning mice were fed a high-fat diet containing 6-gingerol (HFG), zerumbone (HFZ), a characterized rhizome extract of the ginger-related plant Alpinia officinarum Hance (high fat goryankang, HFGK) or no phytochemicals (high-fat control, HFC) for 6 wks and were compared with mice on a low-fat control diet (LFC). Increased adiposity in the HFC group, compared with the LFC group, was significantly (p<0.05) reduced in the HFG and HFGK groups without food intake being affected. Correlation network analysis, including a novel residuals analysis, was utilized to investigate relationships between liver proteomic data, lipid and cholesterol biomarkers and physiological indicators of adiposity. 6-Gingerol significantly increased plasma cholesterol but hepatic farnesyl diphosphate synthetase, which is involved in cholesterol biosynthesis was decreased, possibly by negative feedback. Acetyl-coenzyme A acyltransferase 1 and enoyl CoA hydratase, which participate in the ß-oxidation of fatty acids were significantly (p<0.05) increased by consumption of phytochemical-supplemented diets. CONCLUSION: Dietary ginger phytochemicals target cholesterol metabolism and fatty acid oxidation in mice, with anti-obesogenic but also hypercholesterolemic consequences.

Effects of a high-protein, low-carbohydrate v. high-protein, moderate-carbohydrate weight-loss diet on antioxidant status, endothelial markers and plasma indices of the cardiometabolic profile.

There are concerns that weight-loss (WL) diets based on very low carbohydrate (LC) intake have a negative impact on antioxidant status and biomarkers of cardiovascular and metabolic health. Obese men (n 16) participated in a randomised, cross-over design diet trial, with food provided daily, at approximately 8.3 MJ/d (approximately 70 % of energy maintenance requirements). They were provided with two high-protein diets (30 % of energy), each for a 4-week period, involving a LC (4 % carbohydrate) and a moderate carbohydrate (MC, 35 % carbohydrate) content. Body weight was measured daily, and weekly blood samples were collected. On average, subjects lost 6.75 and 4.32 kg of weight on the LC and MC diets, respectively (P < 0.001, SED 0.350). Although the LC and MC diets were associated with a small reduction in plasma concentrations of retinol, vitamin E (α-tocopherol) and ß-cryptoxanthin (P < 0.005), these were still above the values indicative of deficiency. Interestingly, plasma vitamin C concentrations increased on consumption of the LC diet (P < 0.05). Plasma markers of insulin resistance (P < 0.001), lipaemia and inflammation (P < 0.05, TNF-α and IL-10) improved similarly on both diets. There was no change in other cardiovascular markers with WL. The present data suggest that a LC WL diet does not impair plasma indices of cardiometabolic health, at least within 4 weeks, in otherwise healthy obese subjects. In general, improvements in metabolic health associated with WL were similar between the LC and MC diets. Antioxidant supplements may be warranted if LC WL diets are consumed for a prolonged period.

Functional effects of a common single-nucleotide polymorphism (GPX4c718t) in the glutathione peroxidase 4 gene: interaction with sex.

BACKGROUND: Selenium is essential for health in humans. Selenium is present as selenocysteine in selenoproteins such as the glutathione peroxidases (GPx). Selenocysteine incorporation requires specific structures in the 3'untranslated region (3'UTR) of selenoprotein mRNAs. OBJECTIVE: This study investigated the functional significance of the single-nucleotide polymorphism (SNP) GPx4c718t within the 3'UTR of the GPx4 gene. DESIGN: A selenium supplementation trial was carried out with prospectively genotyped individuals of both homozygote genotypes for this SNP. Blood samples were analyzed at baseline, after a 6-wk supplementation with 100 mug Se as sodium selenite/d, and during a 6-wk washout period. RNA-protein binding studies were carried out in vitro. RESULTS: Both lymphocyte GPx1 protein concentrations and plasma GPx3 activity increased significantly after selenium supplementation in CC but not TT participants. After selenium withdrawal, there was a significant fall in both lymphocyte GPx4 protein concentrations and GPx4 activity in TT but not in CC participants; this effect was modulated by sex. RNA-protein binding assays showed that both T and C variants of transcripts corresponding to the GPx4 3'UTR formed complexes in vitro and that the C variant bound more strongly than did either the T variant or the GPx1 3'UTR. CONCLUSIONS: The GPX4c718t SNP both alters protein binding to the 3'UTR in vitro and influences the concentration of lymphocyte GPx4 and other selenoproteins in vivo. The latter is consistent with competition for selenium in selenoprotein synthesis, and, at low selenium intake, the SNP thus may influence susceptibility to disease.

Extra virgin olive oils increase hepatic fat accumulation and hepatic antioxidant protein levels in APOE-/- mice.

We assessed the effects of Picual and Arbequina olive oil, rich and poor in polyphenols, respectively, on plasma lipid and glucose metabolism, hepatic fat content, and the hepatic proteome in female Apoe-/- mice. Both olive oils increased hepatic fat content and adipophilin levels (p < 0.05), though Picual olive oil significantly decreased plasma triglycerides (p < 0.05). Proteomics identified a range of hepatic antioxidant enzymes that were differentially regulated by both olive oils as compared with palm oil. We found a clear association between olive oil consumption and differential regulation of adipophilin and betaine homocysteine methyl transferase as modulators of hepatic triglyceride metabolism. Therefore, our "systems biology" approach revealed hitherto unrecognized insights into the triglyceride-lowering and anti-atherogenic mechanisms of extra virgin olive oils, wherein the up-regulation of a large array of anti-oxidant enzymes may offer sufficient protection against lesion development and diminish oxidative stress levels instigated by hepatic steatosis.