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Background: Patients with end-stage renal disease (ESRD) exhibit high morbidity as well as mortality for atherosclerotic cardiovascular diseases (CVD). Therefore, we investigated differences in individual lipoprotein classes and subclasses in ESRD patients under chronic high volume hemodiafiltration (HV-HDF) in comparison with a control group. We also assessed the prognosis of these patients and analyzed these parameters after 5 years follow-up. Methods: 57 patients and 50 controls were enrolled. We analysed high density (HDL) and low density (LDL) lipoprotein subfractions using the Quantimetrix Lipoprint(R) system. Subfractions were correlated with selected clinical-biochemical parameters including risk factors for atherosclerotic CVD at the beginning of and after 5 years follow-up. Results: Fourteen patients survived the 5-year follow-up. Follow-up results revealed a shift toward smaller HDL subfractions. In lipoproteins carrying apolipoprotein B, there was a shift of cholesterol from very low density (VLDL) to intermediate density (IDL) lipoproteins and LDLs. Hypolipidaemic therapy did not influence lipoprotein profiles in HV-HDF patients. Conclusions: 1. HV-HDF patients exhibit specific lipid profiles with elevated triacylglycerol, low HDL and LDL and higher content of cholesterol in remnant particles (VLDL and IDL) at the expense of large LDL. HDL subfractions were linked to the number of risk factors for CVD in the control group only. 2. Baseline lipoprotein profiles did not differ between survivors and non-survivors. Non-survivors had higher CRP and lower HDL-C. 3. During the 5 year follow-up period, cholesterol in HDL particles and lipoproteins carrying apolipoprotein B redistributed in survivors towards smaller particles, thus resembling the profile of control patients.

Mixed results have been obtained regarding the level of insulin resistance induced by high-fat diets rich in saturated fatty acids (SFA) when compared to those enriched by polyunsaturated fatty acids (PUFA), and how metabolic effects of marine PUFA of n-3 series, i.e. docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), depend on dietary lipid background. Here we compared two high-fat diets, in which the major lipid constituent was based either on SFA in the form of pork lard (LHF diet) or PUFA of n-6 series (Omega-6) as corn oil (cHF diet). Both cHF and LHF parental diets were also supplemented with EPA+DHA (∼30 g/kg diet) to produce cHF+F and LHF+F diet, respectively. Male C57BL/6N mice were fed the experimental diets for 8 weeks. Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamps in mice fed LHF and cHF diets, and then metabolic effects of cHF+F and LHF+F diets were assessed focusing on the liver and epididymal white adipose tissue (eWAT). Both LHF and cHF induced comparable weight gain and the level of insulin resistance, however LHF-fed mice showed increased hepatic steatosis associated with elevated activity of stearoyl-CoA desaturase-1 (SCD1), and lower plasma triacylglycerol levels when compared to cHF. Despite lowering hepatic SCD1 activity, which was concomitant with reduced hepatic steatosis reaching the level observed in cHF+F mice, LHF+F did not decrease adiposity and the weight of eWAT, and rather further impaired insulin sensitivity relative to cHF+F, that tended to improve it. In conclusion, high-fat diets containing as much as ∼35 weight% as lipids induce similar weight gain and impairment of insulin sensitivity irrespective whether they are based on SFA or Omega-6. Although the SFA-rich diet containing EPA+DHA efficiently reduced hepatic steatosis, it did so without a corresponding improvement in insulin sensitivity and in the absence of effect on adiposity.

Omega-3 polyunsatuarted fatty acids (PUFA) are associated with hypolipidemic and anti-inflammatory effects. However, omega-3 PUFA, usually administered as triacylglycerols or ethyl esters, could also compromise glucose metabolism, especially in obese type 2 diabetics. Phospholipids represent an alternative source of omega-3 PUFA, but their impact on glucose homeostasis is poorly explored. Male C57BL/6N mice were fed for 8 weeks a corn oil-based high-fat diet (cHF) alone or cHF-based diets containing eicosapentaenoic acid and docosahexaenoic acid (~3%; wt/wt), admixed either as a concentrate of re-esterified triacylglycerols (ω3TG) or Krill oil containing mainly phospholipids (ω3PL). Lean controls were fed a low-fat diet. Insulin sensitivity (hyperinsulinemic-euglycemic clamps), parameters of glucose homeostasis, adipose tissue function, and plasma levels of N-acylethanolamines, monoacylglycerols and fatty acids were determined. Feeding cHF induced obesity and worsened (~4.3-fold) insulin sensitivity as determined by clamp. Insulin sensitivity was almost preserved in ω3PL but not ω3TG mice. Compared with cHF mice, endogenous glucose production was reduced to 47%, whereas whole-body and muscle glycogen synthesis increased ~3-fold in ω3PL mice that showed improved adipose tissue function and elevated plasma adiponectin levels. Besides eicosapentaenoic and docosapentaenoic acids, principal component analysis of plasma fatty acids identified palmitoleic acid (C16:1n-7) as the most discriminating analyte whose levels were increased in ω3PL mice and correlated negatively with the degree of cHF-induced glucose intolerance. While palmitoleic acid from Krill oil may help improve glucose homeostasis, our findings provide a general rationale for using omega-3 PUFA-containing phospholipids as nutritional supplements with potent insulin-sensitizing effects.

Obesity in childhood increases the risk of obesity in adulthood and is predictive for the development of metabolic disorders. The fatty acid composition is associated with obesity and obesity-associated disorders. We investigated the relationship between serum fatty acids composition, adiposity, lipids profile, parameters of glucose metabolism and leptin. The study subjects were 380 adolescents aged 15.0-17.9 years. The study's variables included anthropometric measurements, levels of serum lipids and hormonal parameters. Individual fatty acids were determined in plasma by gas-liquid chromatography. Palmitoleic acid (16:1n-7, PA) significantly positively correlated with percentage of body fat. Saturated fatty acids in phospholipids (PL) positively correlated with BMI and percentage of body fat. PA content in all lipids classes positively correlated with total cholesterol (TC), HDL cholesterol, triglycerides (TG) levels. Stearoyl-CoA desaturase (SCD) activity positively correlated with percentage of body fat and positive correlations of SCD and PA level with leptin were found. Plasma PA content and SCD are associated with adiposity and leptin in obese adolescents. No significant correlation between PA level and insulin resistance was found. Palmitoleate positively correlated with TC, HDL cholesterol, TG and LDL cholesterol levels.

Non-alcoholic fatty liver disease (NAFLD) accompanies obesity and insulin resistance. Recent meta-analysis suggested omega-3 polyunsaturated fatty acids DHA and EPA to decrease liver fat in NAFLD patients. Anti-inflammatory, hypolipidemic, and insulin-sensitizing effects of DHA/EPA depend on their lipid form, with marine phospholipids showing better efficacy than fish oils. We characterized the mechanisms underlying beneficial effects of DHA/EPA phospholipids, alone or combined with an antidiabetic drug, on hepatosteatosis. C57BL/6N mice were fed for 7 weeks an obesogenic high-fat diet (cHF) or cHF-based interventions: (i) cHF supplemented with phosphatidylcholine-rich concentrate from herring (replacing 10% of dietary lipids; PC), (ii) cHF containing rosiglitazone (10 mg/kg diet; R), or (iii) PC + R. Metabolic analyses, hepatic gene expression and lipidome profiling were performed. Results showed that PC and PC + R prevented cHF-induced weight gain and glucose intolerance, while all interventions reduced abdominal fat and plasma triacylglycerols. PC and PC + R also lowered hepatic and plasma cholesterol and reduced hepatosteatosis. Microarray analysis revealed integrated down-regulation of hepatic lipogenic and cholesterol biosynthesis pathways by PC, while R-induced lipogenesis was fully counteracted in PC + R. Gene expression changes in PC and PC + R were associated with preferential enrichment of hepatic phosphatidylcholine and phosphatidylethanolamine fractions by DHA/EPA. The complex down-regulation of hepatic lipogenic and cholesterol biosynthesis genes and the antisteatotic effects were unique to DHA/EPA-containing phospholipids, since they were absent in mice fed soy-derived phosphatidylcholine. Thus, inhibition of lipid and cholesterol biosynthesis associated with potent antisteatotic effects in the liver in response to DHA/EPA-containing phospholipids support their use in NAFLD prevention and treatment.

OBJECTIVES Oxidative stress has been implicated in the pathogenesis of chronic pancreatitis (CP) and pancreatic cancer (PC). The study aim was to assess the oxidative stress markers and antioxidant defense system in patients with CP and those with PC. METHODS Activities of superoxide dismutase 1 (SOD1), catalase (CAT), glutathione peroxidase 1 (GPX1), glutathione reductase (GR), arylesterase (PON1-A) and lactonase (PON1-L) activities of paraoxonase 1 (PON1) and concentrations of reduced glutathione, conjugated dienes in low-density lipoprotein (CD/LDL) and oxidized LDL (ox-LDL/LDL) were assessed in 50 PC and 50 CP patients and 50 age and sex-matched controls. RESULTS Comparison of PC and CP groups to controls found the following changes: glutathione peroxidase 1 (GPX1) (-20.2%, -25.5%; P < 0.001), glutathione reductase (GR) (-9.5%, -11.9%; P < 0.05), SOD1 (+22.9%; P < 0.01), CAT (-10.6%; P < 0.05), PON1-A (-34.3%, -16.0%; P < 0.001), PON1-L (-44.2%; -17.0%; P < 0.01), conjugated dienes in LDL (CD/LDL) (+20%, +33.3%; P < 0.05) and ox-LDL/LDL (+42.2%, +14.4%; P < 0.05). The patients with PC had changed activities and levels of SOD1 (+24.2%), CAT (-10.4); P < 0.01), PON1-A (-21.7%), PON1-L (-32.9%), and ox-LDL/LDL (+24.3%); (all P < 0.01) compared with the patients with CP. CONCLUSIONS Reduced antioxidant defense system capacity and increased markers of oxidative stress were found in PC and CP. PON1-L and CAT activities, along with ox-LDL/LDL levels, were the independent factors differentiating the patients with PC from the patients with CP.

Background: This is the second of two review parts aiming at describing the major physiological roles of fatty acids, as well as their applications in specific conditions related to human health. Results: The review included the current literature published in Pubmed up to March 2011. In humans, fatty acids are a principle energy substrate and structural components of cell membranes (phospholipids) and second messengers. Fatty acids are also ligands of nuclear receptors affecting gene expression. Longer-chain (LC) polyunsaturated fatty acids (PUFA), including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid are precursors of lipid mediators such as eicosanoids (prostaglandins, leukotrienes, thromboxanes), resolvins and neuroprotectins. Lipid mediators produced by EPA and DHA (LC n-3 PUFA; mainly found in oily fish) are considered as inflammation-resolving, and thus, fish oil has been characterised as antiinflammatory. Recommendations for EPA plus DHA intake from oily fish vary between 250-450 mg/day. Dietary reference values for fat vary between nutrition bodies, but mainly agree on a low total and saturated fat intake. The existing literature supports the protective effects of LC n-3 PUFA (as opposed to n-6 PUFA and saturated fat) in maternal and offspring health, cardiovascular health, insulin sensitivity, the metabolic syndrome, cancer, critically ill patients, and immune system disorders. Conclusion: Fatty acids are involved in multiple pathways and play a major role in health. Further investigation and a nutrigenomics approach to the effects of these biocompounds on health and disease development are imperative and highlight the importance of environmental modifications on disease outcome.

Adipose tissue has a key role in the development of metabolic syndrome (MS), which includes obesity, type 2 diabetes, dyslipidaemia, hypertension and other disorders. Systemic insulin resistance represents a major factor contributing to the development of MS in obesity. The resistance is precipitated by impaired adipose tissue glucose and lipid metabolism, linked to a low-grade inflammation of adipose tissue and secretion of pro-inflammatory adipokines. Development of MS could be delayed by lifestyle modifications, while both dietary and pharmacological interventions are required for the successful therapy of MS. Then-3 long-chain (LC) PUFA, EPA and DHA, which are abundant in marine fish, act as hypolipidaemic factors, reduce cardiac events and decrease the progression of atherosclerosis. Thus,n-3 LC PUFA represent healthy constituents of diets for patients with MS. In rodentsn-3 LC PUFA prevent the development of obesity and impaired glucose tolerance. The effects ofn-3 LC PUFA are mediated transcriptionally by AMP-activated protein kinase and by other mechanisms.n-3 LC PUFA activate a metabolic switch toward lipid catabolism and suppression of lipogenesis, i.e. in the liver, adipose tissue and small intestine. This metabolic switch improves dyslipidaemia and reduces ectopic deposition of lipids, resulting in improved insulin signalling. Despite a relatively low accumulation ofn-3 LC PUFA in adipose tissue lipids, adipose tissue is specifically linked to the beneficial effects ofn-3 LC PUFA, as indicated by (1) the prevention of adipose tissue hyperplasia and hypertrophy, (2) the induction of mitochondrial biogenesis in adipocytes, (3) the induction of adiponectin and (4) the amelioration of adipose tissue inflammation byn-3 LC PUFA.

The aim of this study was to investigate the effect of the microsomal triglyceride transfer protein (MTP) −493G/T polymorphism on clinical and biochemical parameters in relation to the presence of metabolic syndrome (MS). A group of 270 participants, 143 men and 127 women [50 men/36 women fulfilled the International Diabetes Federation (IDF) criteria of MS], was categorized on the basis of the MTP −493G/T polymorphism: GG homozygotes (Group GG) and carriers of the T allele (Group TT+TG). In men with MS, the presence of the T allele was associated with elevated concentrations of plasma insulin (by 48%, P

Contains fulltext : 144818.pdf (Publisher’s version ) (Open Access) Elevated circulating lipid levels are known risk factors for cardiovascular diseases (CVD). In order to examine the effects of quercetin on lipid metabolism, mice received a mild-high-fat diet without (control) or with supplementation of 0.33% (w/w) quercetin for 12 weeks. Gas chromatography and (1)H nuclear magnetic resonance were used to quantitatively measure serum lipid profiles. Whole genome microarray analysis of liver tissue was used to identify possible mechanisms underlying altered circulating lipid levels. Body weight, energy intake and hepatic lipid accumulation did not differ significantly between the quercetin and the control group. In serum of quercetin-fed mice, triglycerides (TG) were decreased with 14% (p

Background: n-3 polyunsaturated fatty acids, namely docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), reduce the risk of cardiovascular disease and can ameliorate many of obesity-associated disorders. We hypothesised that the latter effect will be more pronounced when DHA/EPA is supplemented as phospholipids rather than as triglycerides. Methodology/Principal Findings: In a 'prevention study', C57BL/6J mice were fed for 9 weeks on either a corn oil-based high-fat obesogenic diet (cHF; lipids ~35% wt/wt), or cHF-based diets in which corn oil was partially replaced by DHA/EPA, admixed either as phospholipids or triglycerides from marine fish. The reversal of obesity was studied in mice subjected to the preceding cHF-feeding for 4 months. DHA/EPA administered as phospholipids prevented glucose intolerance and tended to reduce obesity better than triglycerides. Lipemia and hepatosteatosis were suppressed more in response to dietary phospholipids, in correlation with better bioavailability of DHA and EPA, and a higher DHA accumulation in the liver, white adipose tissue (WAT), and muscle phospholipids. In dietary obese mice, both DHA/EPA concentrates prevented a further weight gain, reduced plasma lipid levels to a similar extent, and tended to improve glucose tolerance. Importantly, only the phospholipid form reduced plasma insulin and adipocyte hypertrophy, while being more effective in reducing hepatic steatosis and low-grade inflammation of WAT. These beneficial effects were correlated with changes of endocannabinoid metabolome in WAT, where phospholipids reduced 2-arachidonoylglycerol, and were more effective in increasing anti-inflammatory lipids such as N-docosahexaenoylethanolamine. Conclusions/Significance: Compared with triglycerides, dietary DHA/EPA administered as phospholipids are superior in preserving a healthy metabolic profile under obesogenic conditions, possibly reflecting better bioavalability and improved modulation of the endocannabinoid system activity in WAT. © 2012 Rossmeisl et al.

To investigate the activities of the main antioxidative enzymes and oxidative stress in women with depressive disorder (DD).In 35 drug-naive women with DD and 35 age matched healthy women enzymes superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GPX1), glutathione reductase (GR) and paraoxonase (PON1), concentrations of conjugated dienes (CD), reduced glutathione (GSH) and anthropometric and clinical data were investigated.Women with DD were found to have decreased activities of GPX1 (p0.05), decreased concentrations of GSH (p0.05), and increased activities of GR (p0.05), CuZnSOD (p0.001), and concentrations of CD (p0.05). Activity of GPX1 was positively correlated with concentration of GSH (p0.05). Concentrations of CD were positively correlated with TG (p0.01).Our set of depressive women was characterized by changes indicating an increased oxidative stress, as well as by certain features of metabolic syndrome.

Metabolic syndrome (MS) is defined by the clustering of several components (MSC), which include abdominal fat accumulation, impaired glucose homeostasis, hypertriglyceridemia, lowered high-density lipoprotein cholesterol, increased blood pressure, and hyperuricemia. Metabolic syndrome is also accompanied by increased oxidative stress and inflammation as well as by altered composition of esterified fatty acids (FA). Therefore, we have investigated 210 men (categorized into six groups with increasing number of MSC) to find trends in the extent of oxidative stress, FA pattern and frequency of pathological alleles of the selected candidate genes for lipid metabolism. Increasing number of MSC was connected with the raised serum glucose and insulin, increased concentrations of conjugated dienes in low-density lipoprotein (all p < 0.0001), and high frequency of e2 and e4 alleles of the apolipoprotein E gene (p < 0.005). However, the last significance was lost after the adjustment for age. The incidence of 54Thr allele for intestinal isoform of the fatty acid-binding protein (FABP-2) gene was comparable in all groups. The most important findings were the raised content of saturated FA and the increased activities of Delta9 and Delta6 desaturases (all p < 0.0001), and the decreased content of polyunsaturated FA n-6 family and the decreased activity of Delta5 desaturase (both p < 0.001) in connection with increasing number of MSC. In conclusion, the severity of MS is connected with the progression of oxidative stress and the unfavorable changes in the FA composition. These changes are independent of the studied gene polymorphisms.

The aim of this study was to study the effect of adding polyunsaturated fatty acid (PUFA) n-3 or placebo (containing oleic acid) to a combined statin-fibrate treatment on plasma lipoproteins, lipoperoxidation, glucose homeostasis, total homocysteine (tHcy) and microalbuminuria (MA) in patients with diabetic dyslipidemia (DDL). Twenty-four patients, who did not fulfill the recommended target lipid values with combined hypolipidemic therapy (pravastatin 20 mg+micronized fenofibrate 200 mg daily), were supplemented with 3.6 g PUFA n-3 daily for 3 months or placebo (olive oil) for the next 3 months. The concentrations of plasma lipids, fatty acid (FA) profiles of phosphatidylcholine (PC), cholesteryl esters (CE) and triglycerides (TG), tHcy levels, concentrations of conjugated dienes (CD) in low-density lipoprotein (LDL), and MA were determined in baseline state, after the PUFA n-3 and placebo treatment period. Supplementation with PUFA n-3 led to a significant decrease in plasma tHcy (-29%, P < .01) and TG (-28%, P < .05) levels, as well as to a significant decrease in MA (-24%, P < .05). The decrease in MA correlated significantly with the increase in total PUFA n-3 (r = -.509, P < or = .05) and docosahexaenoic acid (r = -.52, P < .01) in TG. The concentrations of CD in LDL increased significantly (+15%, P < .05). The supplementation with PUFA n-3 to the combined statin-fibrate treatment in patients with DDL decreased the TG and tHcy levels as well as MA. It could lead to decreased risk of atherothrombosis and delay of diabetic nephropathy onset and progression.

The composition of polyunsaturated fatty acids (PUFAs) in cell membranes and body tissues is altered in metabolic syndrome (MetS) and depressive disorder (DD). Within the cell, fatty acid coenzyme A (CoA) ligases (FACLs) activate PUFAs by esterifying with CoA. The FACL4 isoform prefers PUFAs (arachidonic and eicosapentaenoic acid) as substrates, and the FACL4 gene is mapped to Xq23. We have analyzed the association between the common single nucleotide polymorphism (SNP) (rs1324805, C to T substitution) in the first intron of the FACL4 gene and MetS or DD. The study included 113 healthy subjects (54Males/59Females), 56 MetS patients (34M/22F) and 41 DD patients (7M/34F). In MetS group, T-carriers and patients with CC or C0 (CC/C0) genotype did not differ in the values of metabolic indices of MetS and M/F ratio. Nevertheless, in comparison with CC/C0, the T-allele carriers were characterized by enhanced unfavorable changes in fatty acid metabolism typical for MetS: higher content of dihomogammalinolenic acid (P < 0.05) and lower content of arachidonic acid in plasma phosphatidylcholine (PC) (P = 0.052), lower index of Δ5 desaturation (P < 0.01) and unsaturation index (UI) (P < 0.001). In contrast, DD patients had higher concentrations of plasma glucose, insulin, conjugated dienes and index of insulin resistance, but showed no significant association with the studied SNP. The present study shows that the common SNP (C to T substitution) in the first intron of the FACL4 gene is associated with altered FA composition of plasma phosphatidylcholines in patients with MetS.