Endothelial HO-1 induction by model TG-rich lipoproteins is regulated through a NOX4-Nrf2 pathway

Circulating levels of chylomicron remnants (CMRs) increase postprandially and their composition directly reflects dietary lipid intake. These TG-rich lipoproteins likely contribute to the development of endothelial dysfunction, albeit via unknown mechanisms. Here, we investigated how the FA composition of CMRs influences their actions on human aortic endothelial cells (HAECs) by comparing the effects of model CMRs—artificial TG-rich CMR-like particles (A-CRLPs)—containing TGs extracted from fish, DHA-rich algal, corn, or palm oils. HAECs responded with distinct transcriptional programs according to A-CRLP TG content and oxidation status, with genes involved in antioxidant defense and cytoprotection most prominently affected by n-3 PUFA-containing A-CRLPs. These particles were significantly more efficacious inducers of heme oxygenase-1 (HO-1) than n-6 PUFA corn or saturated FA-rich palm CRLPs. Mechanistically, HO-1 induction by all CRLPs requires NADPH oxidase 4, with PUFA-containing particles additionally dependent upon mitochondrial reactive oxygen species. Activation of both p38 MAPK and PPARβ/δ culminates in increased nuclear factor erythroid 2-related factor 2 (Nrf2) expression/nuclear translocation and HO-1 induction. These studies define new molecular pathways coupling endothelial cell activation by model CMRs with adaptive regulation of Nrf2-dependent HO-1 expression and may represent key mechanisms through which dietary FAs differentially impact progression of endothelial dysfunction

High-fat meals rich in EPA plus DHA compared with DHA only have differential effects on postprandial lipemia and plasma 8-isoprostane F-2 alpha concentrations relative to a control high-oleic acid meal: a randomized controlled trial

Background: Eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) supplementation has beneficial cardiovascular effects, but postprandial influences of these individual fatty acids are unclear. Objectives: The primary objective was to determine the vascular effects of EPA + DHA compared with DHA only during postprandial lipemia relative to control high–oleic acid meals; the secondary objective was to characterize the effects of linoleic acid–enriched high-fat meals relative to the control meal. Design: We conducted a randomized, controlled, double-blind crossover trial of 4 high-fat (75-g) meals containing 1) high–oleic acid sunflower oil (HOS; control), 2) HOS + fish oil (FO; 5 g EPA and DHA), 3) HOS + algal oil (AO; 5 g DHA), and 4) high–linoleic acid sunflower oil (HLS) in 16 healthy men (aged 35–70 y) with higher than optimal fasting triacylglycerol concentrations (mean ± SD triacylglycerol, 1.9 ± 0.5 mmol/L). Results: Elevations in triacylglycerol concentration relative to baseline were slightly reduced after FO and HLS compared with the HOS control (P < 0.05). The characteristic decrease from baseline in plasma nonesterified fatty acids after a mixed meal was inhibited after AO (Δ 0–3 h, P < 0.05). HLS increased the augmentation index compared with the other test meals (P < 0.05), although the digital volume pulse–reflection index was not significantly different. Plasma 8-isoprostane F(2α) analysis revealed opposing effects of FO (increased) and AO (reduced) compared with the control (P < 0.05). No differences in nitric oxide metabolites were observed. Conclusions: These data show differential postprandial 8-isoprostane F(2α) responses to high-fat meals containing EPA + DHA–rich fish oil compared with DHA-rich AO, but these differences were not associated with consistent effects on postprandial vascular function or lipemia. More detailed analyses of polyunsaturated fatty acid–derived lipid mediators are required to determine possible divergent functional effects of single meals rich in either DHA or EPA. This trial was registered at clinicaltrials.gov as NCT01618071

Differential modulation of hepatic very low-density lipoprotein secretion by triacylglycerol-rich lipoproteins derived from different oleic-acid rich dietary oils

Minor components from dietary oils can modulate the atherogenic response of the TAG-rich lipoproteins (TRL) in which they are transported. In the present study we investigated the influence of TRL isolated from man after the intake of oleic acid-rich oils with different minor component compositions on VLDL secretion by rat primary hepatocytes. TRL were isolated from nine men after the intake of meals enriched with high-oleic sunflower oil (HOSO) or virgin olive oil (VOO) or VOO enriched with minor components (EVO). TRL were incubated with rat primary hepatocytes and the lipid accumulation was analysed in the cells and the secreted VLDL. The expression of genes for proteins related to hepatic lipid metabolism and VLDL production was also measured. Incubation of hepatocytes with TRL derived from HOSO as compared to VOO led to lower intracellular lipid accumulation and VLDL production despite higher mRNA expression for diacylglycerol-acyltransferase, microsomal TAG transfer protein, apoB and PPARα. When TRL derived from EVO were used there were no changes in VLDL secretion. These results suggest that incorporation of minor components from dietary high-oleic oils into TRL modulates the effect of these atherogenic particles on VLDL secretion. © 2007 The Authors.This work was supported by funds from Comision Interministerial de Ciencia y Tecnologia (CYCIT, AGL2005-00 572), Fondo de Investigaciones Sanitarias (FIS. Red Corporativa ISCIII G03/140-2002) and a Juan de la Cierva contract to J. S. P.Peer Reviewe

Abundance changes and habitat availability drive species’ responses to climate change

There is little consensus as to why there is so much variation in the rates at which different species’ geographic ranges expand in response to climate warming[1,2]. Here, we show for British butterfly species that the relative importance of species’ abundance trends and habitat availability vary over time. Species with high habitat availability expanded more rapidly from the 1970s to mid-1990s, when abundances were generally stable, whereas habitat availability effects were confined to the subset of species with stable abundances from the mid-1990s to 2009, when abundance trends were generally declining. This suggests that stable (or positive) abundance trends are a prerequisite for range expansion. Given that species’ abundance trends vary over time[3] for non-climatic as well as climatic reasons, assessment of abundance trends will help improve predictions of species’ responses to climate change, and help understand the likely success of different conservation strategies for facilitating their expansions

Understanding Postprandial Inflammation and Its Relationship to Lifestyle Behaviour and Metabolic Diseases

Postprandial hyperlipidemia with accumulation of remnant lipoproteins is a common metabolic disturbance associated with atherosclerosis and vascular dysfunction, particularly during chronic disease states such as obesity, the metabolic syndrome and, diabetes. Remnant lipoproteins become attached to the vascular wall, where they can penetrate intact endothelium causing foam cell formation. Postprandial remnant lipoproteins can activate circulating leukocytes, upregulate the expression of endothelial adhesion molecules, facilitate adhesion and migration of inflammatory cells into the subendothelial space, and activate the complement system. Since humans are postprandial most of the day, the continuous generation of remnants after each meal may be one of the triggers for the development of atherosclerosis. Modulation of postprandial lipemia by lifestyle changes and pharmacological interventions could result in a further decrease of cardiovascular mortality and morbidity. This paper will provide an update on current concepts concerning the relationship between postprandial lipemia, inflammation, vascular function, and therapeutic options

High fat diet-induced non alcoholic fatty liver disease in rats is associated with hyperhomocysteinemia caused by down regulation of the transsulphuration pathway

<p>Abstract</p> <p>Background</p> <p>Hyperhomocysteinemia (HHcy) causes increased oxidative stress and is an independent risk factor for cardiovascular disease. Oxidative stress is now believed to be a major contributory factor in the development of non alcoholic fatty liver disease, the most common liver disorder worldwide. In this study, the changes which occur in homocysteine (Hcy) metabolism in high fat-diet induced non alcoholic fatty liver disease (NAFLD) in rats were investigated.</p> <p>Methods and results</p> <p>After feeding rats a standard low fat diet (control) or a high fat diet (57% metabolisable energy as fat) for 18 weeks, the concentration of homocysteine in the plasma was significantly raised while that of cysteine was lowered in the high fat as compared to the control diet fed animals. The hepatic activities of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CGS), the enzymes responsible for the breakdown of homocysteine to cysteine via the transsulphuration pathway in the liver, were also significantly reduced in the high fat-fed group.</p> <p>Conclusions</p> <p>These results indicate that high fat diet-induced NAFLD in rats is associated with increased plasma Hcy levels caused by down-regulation of hepatic CBS and CGL activity. Thus, HHcy occurs at an early stage in high fat diet-induced NAFLD and is likely to contribute to the increased risk of cardiovascular disease associated with the condition.</p