Plasma LDL Levels Research Articles

Utilization of Untreated and Treated Olive Pulp Meal in Feeding Broiler Chicks الاستفادة من مسحوق تفل الزيتون المعامل وغير المعامل في تغذية کتاکيت التسمين

Two hundred and ten unsexed one day old Cobb 500 broiler chicks were used until 6 weeks of age to study the effect of Trichoderma reesei fungus(108 CFU /ml)and sodium hydroxide(NaOH, 10 g/kg OPM)addition in olive pulp meal(OPM)broiler diets on growth rate, digestion coefficients, some blood parameters, carcass traits and the economic efficiency of feed. The chicks were randomly distributed into seven equal treatments, 30 chicks/treatment with three replicates each. The treatments were control, C (The basal diet without OPM),T1(Basal diet+12% OPM),T2 (Basal diet +12% OPM+fungus), T3 (Basal diet+12% OPM+NaOH), T4 (Basal diet +15% OPM), T5 (Basal diet + 15% OPM + fungus) and T6 (Basal diet + 15% OPM + NaOH). The treated OPM with NaOH showed similar results of body weight and gain as the control .The control treatment recorded the highest value(P<0.01)of feed intake. The best value (P<0.05) of feed conversion ratio was noticed with T3. The treated OPM showed a significant (P<0.05) in CP, CF, NFE, DCP, TDN (%) and ME(kcal/kg)compared to the untreated OPM; The treated and untreated OPM increased plasma cholesterol, LDL and HDL levels, While Triglycerides were decreased with all treatments compared to the control. All treatments recorded high values (P<0.05) of gizzard (%), cecum weight and cecum length compared to the control, the treated and untreated OPM decreased the feed cost/kg meat and increased the net return/kg meat.The results concluded that treating OPM with NaOH or fungus improved the nutritive value of OPM without any adverse effects on birds.

LDLR gene polymorphism (rs688) affects susceptibility to cardiovascular disease in end-stage kidney disease patients

BackgroundThe low-density lipoprotein receptor (LDLR) plays a significant role in maintaining the cellular cholesterol homeostasis. Mutations in the LDLR gene can lead to a significant rise in plasma LDL levels that may result in an increased risk of atherosclerosis and coronary heart disease. The purpose of this study was to assess the potential association of the LDLR rs688 polymorphism with cardiovascular disease (CVD) in patients with end-stage kidney disease (ESKD) undergoing hemodialysis.MethodsIn this case-control study the polymorphism was genotyped by the allele specific PCR method in 800 patients with ESKD and 500 healthy controls. The genotype and allele distribution was compared in subgroups of patients with CVD (552) versus those without CVD (248).ResultsA significant difference was observed in genotype distribution among ESKD patients and healthy controls. The frequencies of the T allele and TT genotype in ESKD group were significantly higher, with OR (95% CI) 2.2 (1.87–2.6), p < 0.0001 and 5.84 (3.94–8.65), p < 0.0001, respectively. In the he ESKD cohort the distribution of the rs688 was compared between CVD+ and CVD- subgroups. A strong association of the polymorphism with the CVD risk was observed in this analysis. The frequencies of the T allele and TT genotype were significantly higher in CVD+ subgroup, with OR (95% CI) 3.4 (2.71–4.26), p < 0.0001 and 13.2 (7.87–22.09), p < 0.0001, respectively. A multivariate logistic regression analysis was performed to estimate the association between rs688 T variant and risk of CVD. After adjustment for age, sex, BMI, hypertension and diabetes, both CT and TT genotypes were associated with an increased risk of developing CVD in the dominant, recessive and codominant models of inheritance. No significant differences in serum LDL cholesterol levels were found when compared between genotypes.ConclusionsThe present study is the first to demonstrate the association of the LDLR gene polymorphism with increased susceptibility to cardiovascular disease in ESKD patients. This finding needs further investigation to confirm that LDLR rs688 might be a novel genetic risk factor with some prognostic capacity for CVD in ESKD patients.

Antioxidant Effect of Lonicera caerulea L. in the Cardiovascular System of Obese Zucker Rats

Lonicera caerulea L. (Loni) represents a promising source of beneficial polyphenols with therapeutical potential in cardiovascular diseases. We aimed to study the effects of Loni and coenzyme Q10 (CoQ10) on selected cardiometabolic parameters and NO/ROS balance in obese Zucker rats. Male Zucker rats were divided into the control group and groups treated with CoQ10 (30 mg/kg/day) or Loni (5 g/kg/day) for 6 weeks. Blood pressure, body weight, heart weight, and plasma lipid profile were determined. NOS activity and protein expressions of eNOS, SOD, NADPH oxidase, and NF-kappa B were measured in the heart and aorta. Neither body weight nor blood pressure were significantly changed after six weeks of Loni or CoQ10 treatment. Both Loni and CoQ10 decreased the plasma LDL level. Moreover, Loni decreased the total cholesterol level. The total NOS activity did not change in the heart after the treatments. However, in the aorta, Loni treatment increased NOS activity and protein expression of SOD and decreased expressions of NADPH oxidase and NF-kappa B compared to both the control and CoQ10 groups. There were no changes in the eNOS protein expression within the groups. In conclusion, it seems that the antioxidant effect of Loni was responsible for both the decrease of plasma LDL and the total cholesterol levels and the increase of vascular NOS activity.

Some Factors Affecting Blood Parameters of Broiler Chickens

The present study was aimed to investigate the effect of flock age, air pressure during incubation period and litter types on blood plasma constituents of broiler chicks. A total number of 600 one day old hatching chicks (ROSS 308) were taken randomly nearly a similar in live body weight were used in this study. Chicks were randomly divided into equal 12 groups in a 2×2×3 factorial arrangement experiment according to flock age (younger breeder flock 33 WKS and older breeder flock 43 WKS), air pressure (normal 100719 and high, 1011000 Pascal) and three litter types (wood shaving, plastic and sand). The results obtained showed that, broiler chicks produced from younger breeder flock recorded significantly (p < 0.001) the higher levels of plasma total protein (TP), albumin (A) and globulin (G). However, broiler chicks produced from older breeder flock found to be significantly decreased levels of plasma triglycerides, total cholesterol, low density lipoprotein, aspartate aminotransferase (AST), alanine aminotransferase (ALT) creatinine, uric acid and malondialdehyde (MDA).Broiler chicks produced from eggs incubated at high air pressure (HAP) showed significant(p < 0.001) the higher levels of plasma TP, A , G and MDA. While, chicks produced from eggs incubated at low air pressure decreased significantly the levels of plasma triglycerides, total cholesterol, LDL, AST, ALT, creatinine, uric acid and significantly increased plasma levels of high density lipoprotein (HDL) and glutathione peroxidase (GPX). Blood plasma constituents significantly varied due to the effect of litter type, it was found that broiler chicks raised on sand litter type showed the higher levels of plasma TP, A and G. While, the lower levels of plasma triglycerides, total cholesterol, LDL, AST, ALT, creatinine, uric acid, MDA and higher levels of HDL and GPX were found in broiler chicks raised on plastic (PL) litter type. According to the interaction between the studied factors, it could be concluded that the interaction between 43 WKS × HAP ×PL seemed to be adequate to achieve the favorable results of blood parameters.

Antibody-Based Therapeutics for Atherosclerosis and Cardiovascular Diseases.

Cardiovascular disease is the leading cause of death worldwide, and its prevalence is increasing due to the aging of societies. Atherosclerosis, a type of chronic inflammatory disease that occurs in arteries, is considered to be the main cause of cardiovascular diseases such as ischemic heart disease or stroke. In addition, the inflammatory response caused by atherosclerosis confers a significant effect on chronic inflammatory diseases such as psoriasis and rheumatic arthritis. Here, we review the mechanism of action of the main causes of atherosclerosis such as plasma LDL level and inflammation; furthermore, we review the recent findings on the preclinical and clinical effects of antibodies that reduce the LDL level and those that neutralize the cytokines involved in inflammation. The apolipoprotein B autoantibody and anti-PCSK9 antibody reduced the level of LDL and plaques in animal studies, but failed to significantly reduce carotid inflammation plaques in clinical trials. The monoclonal antibodies against PCSK9 (alirocumab, evolocumab), which are used as a treatment for hyperlipidemia, lowered cholesterol levels and the incidence of cardiovascular diseases. Antibodies that neutralize inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-17, and IL-12/23) have shown promising but contradictory results and thus warrant further research.

Menaquinone 4 increases plasma lipid levels in hypercholesterolemic mice

In calcific aortic valve disease (CAVD) progressive valvular calcification causes aortic valve dysfunction. CAVD has several risk factors such as age and dyslipidemia. Vitamin K was shown to inhibit vascular calcification in mice and valvular calcification in patients with CAVD. We studied the effect of menaquinone 4 (MK4/vitamin K2) on valvular calcification in the hypercholesterolemic mouse model of CAVD. LDLr−/−ApoB100/100 male mice were fed with a Western diet for 5 months, with (n = 10) or without (n = 10) added 0.2 mg/g MK4. Body weight gain was followed weekly. Morphology of aortic valves and liver was assessed with immunohistochemistry. Plasma cholesterol levels and cytokines from hepatic tissue were assessed in the end of the study. Hepatic gene expression of lipid metabolism regulating genes were assessed after 18 h diet. MK4 exacerbated the lipoprotein lipid profile without affecting aortic valve morphology in hypercholesterolemic LDLr−/− ApoB100/100 mice. The MK4-containing WD diet increased plasma levels of LDL and triglycerides, hepatic steatosis, and mRNA expression of genes required for triglyceride and cholesterol synthesis. MK4 diminished levels of several cytokines and chemokines in liver, including IL-6, TNFα and MCP1, as measured by hepatic cytokine array. Consequently, MK4 may exert non-beneficial effects on circulating lipid levels, especially in hypercholesterolemic individuals.

Ganoderma lucidum ethanol extract abrogates metabolic syndrome in rats: In vivo evaluation of hypoglycemic, hypolipidemic, hypotensive and antioxidant properties

Metabolic syndrome (MetS), characterized by hyperglycemia, dyslipidemia, hypertension, and central obesity remains a global menace. Ganoderma lucidum possesses various beneficial bioactivities. This study, thus, evaluated the efficacy of Ganoderma lucidum ethanol extract (GLEE) against MetS complications in rats. Thirty male rats were randomized into six groups (n = 5): Control, MetS control, MetS + standard drugs, MetS + GLEE (26 mg/kg), MetS + GLEE (44 mg/kg), and MetS + GLEE (70 mg/kg). Bodyweight, blood sugar, and pressure were monitored. Animals were sacrificed following two weeks of GLEE treatment post-MetS induction. Blood, pancreas, heart, liver, and kidney were collected for biochemical and histopathological analyses. Plasma triacylglycerol (TAG), plasma and lipoproteins (HDL and LDL) cholesterol (CHOL) levels, and activities of superoxide dismutase (SOD), and catalase (CAT), as well as malondialdehyde (MDA) level, were estimated in the pancreas, heart, liver, and kidneys. GLEE Phyto-analysis revealed terpenoids, flavonoids, alkaloids, and saponins. A dose-dependent total antioxidant capacity and, a near dose-dependent DPPH radical scavenging, and ferric ion reducing ability were exhibited by GLEE in vitro. GLEE (70 mg/kg) reversed significantly (p < 0.05) the MetS-induced hyperglycemia and hypertension. Furthermore, increments in plasma TAG, CHOL, LDL, and MDA levels reduced dose-dependently. Increased CAT (pancreas and heart) and SOD (the four organs) activities and, NRF2 protein levels significantly reduced in GLEE-treated group relative to MetS control. Histological evidence suggests that GLEE abated the MetS- induced cytomorphological derangements in the organs. This study concludes that GLEE may be a viable regimen against MetS and its attendant complications.

On the possible existence of a liver LDL-ostat, and its malfunctioning in familial hypercholesterolemia

The investigation of familial hypercholesterolemia (FH) and its relationship to atherosclerosis has led to enormous scientific and medical progress, including the identification of genetic defects underlying FH, the elucidation of molecular mechanisms crucial for cellular cholesterol homeostasis and the development of current pharmaceutical tools for FH treatment (which are directed at increasing LDL uptake). These successes also led to the establishment of a model centered on cellular rather than whole organism processes, and a view of FH as resulting from a deficiency in LDL uptake. On the other hand, whole organism fluxes of cholesterol (like those of other nutrients) are centered on the liver, LDL (ultimately derived from the liver) is the main cholesterol transporter in plasma, and there is evidence of evolutionary pressure favoring mechanisms to maintain LDL plasma concentrations. Furthermore, the alterations in cellular metabolism observed in FH are consistent with a coordinated response by the liver to increase the levels of plasma LDL, suggesting that a signaling defect (rather than an uptake deficiency) is the fundamental problem underlying hypercholesterolemia – an hypothesis that explains the occurrence of hypercholesterolemia in CESD, despite normal LDL binding and uptake. I therefore propose that the liver contains a mechanism to assess and regulate plasma levels of LDL (an “LDL-ostat”), and that hypercholesterolemia is caused by defects in it. This model has implications for future research directions, and suggests alternative therapeutic approaches, particularly centered on efforts to restore LDL measurement/signaling (rather than its uptake), some of which are in stark contrast to those currently in use.

Fructose-Induced Intestinal Microbiota Shift Following Two Types of Short-Term High-Fructose Dietary Phases.

High consumption of fructose and high-fructose corn syrup is related to the development of obesity-associated metabolic diseases, which have become the most relevant diet-induced diseases. However, the influences of a high-fructose diet on gut microbiota are still largely unknown. We therefore examined the effect of short-term high-fructose consumption on the human intestinal microbiota. Twelve healthy adult women were enrolled in a pilot intervention study. All study participants consecutively followed four different diets, first a low fructose diet (< 10 g/day fructose), then a fruit-rich diet (100 g/day fructose) followed by a low fructose diet (10 g/day fructose) and at last a high-fructose syrup (HFS) supplemented diet (100 g/day fructose). Fecal microbiota was analyzed by 16S rRNA sequencing. A high-fructose fruit diet significantly shifted the human gut microbiota by increasing the abundance of the phylum Firmicutes, in which beneficial butyrate producing bacteria such as Faecalibacterium, Anareostipes and Erysipelatoclostridium were elevated, and decreasing the abundance of the phylum Bacteroidetes including the genus Parabacteroides. An HFS diet induced substantial differences in microbiota composition compared to the fruit-rich diet leading to a lower Firmicutes and a higher Bacteroidetes abundance as well as reduced abundance of the genus Ruminococcus. Compared to a low-fructose diet we observed a decrease of Faecalibacterium and Erysipelatoclostridium after the HFS diet. Abundance of Bacteroidetes positively correlated with plasma cholesterol and LDL level, whereas abundance of Firmicutes was negatively correlated. Different formulations of high-fructose diets induce distinct alterations in gut microbiota composition. High-fructose intake by HFS causes a reduction of beneficial butyrate producing bacteria and a gut microbiota profile that may affect unfavorably host lipid metabolism whereas high consumption of fructose from fruit seems to modulate the composition of the gut microbiota in a beneficial way supporting digestive health and counteracting harmful effects of excessive fructose.

The relationship between circulating lipids and breast cancer risk: A Mendelian randomization study.

A number of epidemiological and genetic studies have attempted to determine whether levels of circulating lipids are associated with risks of various cancers, including breast cancer (BC). However, it remains unclear whether a causal relationship exists between lipids and BC. If alteration of lipid levels also reduced risk of BC, this could present a target for disease prevention. This study aimed to assess a potential causal relationship between genetic variants associated with plasma lipid traits (high-density lipoprotein, HDL; low-density lipoprotein, LDL; triglycerides, TGs) with risk for BC using Mendelian randomization (MR). Data from genome-wide association studies in up to 215,551 participants from the Million Veteran Program (MVP) were used to construct genetic instruments for plasma lipid traits. The effect of these instruments on BC risk was evaluated using genetic data from the BCAC (Breast Cancer Association Consortium) based on 122,977 BC cases and 105,974 controls. Using MR, we observed that a 1-standard-deviation genetically determined increase in HDL levels is associated with an increased risk for all BCs (HDL: OR [odds ratio] = 1.08, 95% confidence interval [CI] = 1.04-1.13, P < 0.001). Multivariable MR analysis, which adjusted for the effects of LDL, TGs, body mass index (BMI), and age at menarche, corroborated this observation for HDL (OR = 1.06, 95% CI = 1.03-1.10, P = 4.9 × 10-4) and also found a relationship between LDL and BC risk (OR = 1.03, 95% CI = 1.01-1.07, P = 0.02). We did not observe a difference in these relationships when stratified by breast tumor estrogen receptor (ER) status. We repeated this analysis using genetic variants independent of the leading association at core HDL pathway genes and found that these variants were also associated with risk for BCs (OR = 1.11, 95% CI = 1.06-1.16, P = 1.5 × 10-6), including locus-specific associations at ABCA1 (ATP Binding Cassette Subfamily A Member 1), APOE-APOC1-APOC4-APOC2 (Apolipoproteins E, C1, C4, and C2), and CETP (Cholesteryl Ester Transfer Protein). In addition, we found evidence that genetic variation at the ABO locus is associated with both lipid levels and BC. Through multiple statistical approaches, we minimized and tested for the confounding effects of pleiotropy and population stratification on our analysis; however, the possible existence of residual pleiotropy and stratification remains a limitation of this study. We observed that genetically elevated plasma HDL and LDL levels appear to be associated with increased BC risk. Future studies are required to understand the mechanism underlying this putative causal relationship, with the goal of developing potential therapeutic strategies aimed at altering the cholesterol-mediated effect on BC risk.

The Association between the Plasma Sugar and Lipid Profile with the Gene Expression of the Regulatory Protein of mTOR (Raptor) in Patients with Rheumatoid Arthritis

ABSTRACT Background Rheumatoid arthritis (RA) is an autoinflammatory and self-perpetuating disease with both articular and extra-articular manifestations, such as cardiovascular complications, which are the leading cause of mortality and morbidity in RA patients. Impaired sugar and lipid metabolism are considered as the critical risk factors for cardiovascular disease (CVD). Regarding the regulatory function of Raptor in the immunometabolism, in this study, we evaluated the association between plasma sugar and lipid profiles with the gene expression of Raptor and the cytokine tumor necrosis factor-α (TNF-α), as an inflammatory mediator, in peripheral blood leukocyte of RA patients. Material and methods Thirty-five RA patients who received combinational disease modified anti-rheumatoid drugs (DMARD) regimen and thirty healthy subjects enrolled in this study. The gene expression of Raptor was assessed by the real-time PCR method, and the Plasma levels of glucose and lipids, as well as TNF-α, were obtained using Hitachi device and enzyme-linked immunosorbent assay (ELISA) technique, respectively. Results The gene expression of Raptor was reduced significantly in RA patients compared to the healthy subjects (p = .001). The plasma level of HDL was significantly higher in RA patients than the control group (p = .001), while the plasma level of LDL was reduced significantly in these patients (p = .001). Conclusion In our study, the reduced gene expression of Raptor may contribute to the impaired immunometabolism in RA patients, which is independent of plasma sugar and lipid profile.

Daily White kwao krua dietary supplement alleviates LDL oxidative susceptibility, plasma LDL level and improves vasculature in a hypercholesterolemia rabbit model

Background and aimWhite kwao krua is an edible plant that grows in Southeast Asia. It is very rich in natural phytoestrogens. Previous clinical studies revealed that the use of White kwao krua as a hormone replacement therapy has beneficial effects on the lipid profile of menopause women. In this present study, we utilized the hypercholesterolemia rabbit model to demonstrate the effect of White kwao krua on the daily intake of high-fat diet. Experimental procedureWe induced hypercholesterolemia in rabbits by feeding with high-fat diet (1% cholesterol-containing diet). The animals were maintained 12 weeks for the experimentation. The White kwao krua supplement was administered 100 mg/kg/day, and the effects were monitored comparing with Statins and turmeric. Blood was collected periodically to monitor the plasma cholesterol level and the oxidative susceptibility of isolated LDL-cholesterol. At the end of the experiment, the aorta was collected from the animal and performed endothelial-dependent relaxation and endothelial-independent relaxation assays. The relative ratio of intima to media layer was microscopically evaluated from hematoxylin/eosin-stained tissues. Results and conclusionWe showed that the White kwao krua supplement reduced LDL-cholesterol about 40% compared with high-fat diet consumption alone. Administration of White kwao krua had significantly prolonged the susceptibility of LDL-cholesterol to oxidation. Besides, it led to the improvement of vascular function by recovering endothelium-dependent relaxation and alleviating vascular structure impairment induced by high-fat dietary intake. Together, we suggest that White kwao krua should be used as a dietary supplement to reduce the atherogenesis in high-fat dietary consumption. SectionDietary therapy/nutrients supplements. TaxonomyInflammation, Disease.

Comparison of interleukin-6, C-reactive protein, and low-density lipoprotein cholesterol as biomarkers of residual risk in contemporary practice: secondary analyses from the Cardiovascular Inflammation Reduction Trial.

In epidemiologic cohorts initiated >30 years ago, inflammatory biomarkers, such as interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) were shown to independently predict future cardiovascular events with a magnitude of effect comparable to that of low-density lipoprotein cholesterol (LDLC). Whether aggressive contemporary therapy for atherosclerosis has altered these relationships is unknown yet has major implications for future drug development. Interleukin-6, hsCRP, and LDLC were measured at baseline in up to 4168 North American patients enrolled in the contemporary Cardiovascular Inflammation Reduction Trial with prior myocardial infarction or multivessel coronary disease who additionally had diabetes or metabolic syndrome and were followed for a period of up to 5 years for incident major recurrent cardiovascular events and all-cause mortality. Three-quarters of the cohort were previously revascularized and the great majority was taking statins, angiotensin blocking agents, beta-blockers, and antithrombotic agents. Participants were randomly allocated to low-dose methotrexate 15 mg weekly or to placebo. Randomized use of methotrexate had no effect on event rates nor plasma levels of IL-6, hsCRP, or LDL over time. Yet, baseline levels of IL-6, hsCRP, and LDLC were all predictors of major recurrent cardiovascular events; adjusted hazard ratios [HR; 95% confidence interval (CI)] for the lowest to highest baseline quartiles of IL-6 were 1.0 (referent), 1.66 (1.18-2.35), 1.92 (1.36-2.70), and 2.11 (1.49-2.99; P < 0.0001), while adjusted HRs for increasing quartiles of hsCRP were 1.0 (referent), 1.28 (0.92-1.79), 1.73 (1.25-2.38), and 1.79 (1.28-2.50; P < 0.0001) and adjusted HRs for increasing quartiles of LDLC were 1.0 (referent), 1.12 (0.78-1.62), 1.25 (0.87-1.79), and 2.38 (1.72-3.30; P < 0.0001). Effect estimates were not statistically different in these analyses for comparisons between IL-6, hsCRP, or LDLC, although IL-6 was the strongest predictor of all-cause mortality. The highest absolute risks were observed among those with elevated levels of both cholesterol and inflammation [HR 6.4 (95% CI 2.9-14.1) for those in the top quartiles of baseline IL-6 and LDLC, HR 4.9 (95% CI 2.6-9.4) for those in the top quartiles of baseline hsCRP and LDLC, both P < 0.0001]. Despite aggressive contemporary secondary prevention efforts, the relationships between inflammation, cholesterol, and cardiovascular risk are largely unchanged from those described two decades ago. These data are consistent with the hypothesis that future treatments for atherosclerosis may require a combination of inflammation inhibition and additional cholesterol reduction. ClinicalTrials.gov NCT01594333.

The effects of brain-friendly diet on cognitive performance (Brave study)

AbstractIntroduction:Cognitive performance is related to lipid and glucose metabolism and metabolic activation that are regulated by diet. The Brave study has shown beneficial effects of brain-friendly diet (Brainfood) on metabolic health in office workers with elevated metabolic risk. We further examined the effects of Brainfood on cognitive performance.Materials and methods:We conducted a diet-switch, 4-week intervention study on 84 volunteers with elevated plasma LDL levels in pre-screening. During the control period participants continued their habitual eating pattern and were offered an optional lunch following western-type diet, and they did not receive nutritional guidance. In Brainfood period, lunch, snack and breakfast offering was optimised for the quality of carbohydrates and fat and the intake of salt and protein. Educated nutritionist instructed the participants to follow the Brainfood diet and regular meal pattern.Participants kept a 3-day food record at the end of control and Brainfood periods. For each participant, we calculated the Brainfood ratio comparing the total frequencies of consumption of brain-friendly and brain-unfriendly foods. We ranked the subjects also according to the change in brain-friendly nutrient intake (saturated fat, polyunsaturated fat, fibre, sugar and salt) from control to Brainfood period.Cognitive performance (cognitive control and flexibility, attention, inhibition, learning, and memory) were measured with a combination of traditional standardized neuropsychological tests (Bourdon-Wiersma double task, Stroop Colour and Word Test, WMS-III: Letter-Number Sequencing, Rey Auditory Verbal Learning Test) and modern computer and mobile tests (Flexible Attention Test FAT, N-Back task and Task-switching task) before and after the Brainfood diet. In addition, participants evaluated their vigilance, task load and performance after each test with the Karolinska Sleepiness Scale (KSS) and NASA Task Load Index (NASA-TLX).We compared the change in cognitive performance before and after Brainfood diet between the subgroups with the highest and lowest Brainfood ratio and the highest and lowest brain-friendly nutrient intake using repeated measures analysis of variance.Results:Brainfood diet reduced intakes of saturated fat and salt, and increased intakes of polyunsaturated fat, fibre, vitamin C and D, iron and magnesium (p &lt; 0,03). Participants with the highest Brainfood ratio improved reaction time (FAT; p-value for interaction 0,01, multiple comparison correction not applied), switch cost (Task-switching; p = 0,02) and inhibition tendency (Stroop; p = 0,047). Better dietary fat quality decreased self-reported physical strain (NASA-TLX; p-values &lt; 0,007), and higher fibre intake decreased self-reported sleepiness (KSS; p = 0,033).Discussion:Brainfood diet may positively affect cognitive performance in office workers with elevated metabolic risk.

The effects of a brain-friendly diet on metabolic and physiological parameters and cognitive performance (Brave study)

AbstractCognitive performance is related to lipid and glucose metabolism and metabolic activation that are regulated by diet. Further, there is good evidence to support that change in lifestyle, for instance in diet, may promote cognitive health. However, vast majority of the existing studies have focused on children or older adults. We studied the effects of a brain-friendly diet (Brainfood) on metabolic and physiological parameters and cognitive performance in office workers at assumed metabolic risk. We conducted a diet-switch, 4-week intervention study on 84 volunteers with elevated plasma LDL levels in pre-screening. The brainfood diet was planned to be optimal for metabolism and cognitive function; special attention was paid for regular meal frequency, a well-balanced light lunch at work and optimised recipes ensuring quality of carbohydrates and fat, and sufficient protein amount. The control diet was a typical western diet. Breakfast supplies, lunch and afternoon snacks were provided to participants, and they received nutritional counselling. Participants' sociodemographic characteristics, such as age and sex, were queried in the beginning of the intervention. Plasma samples were collected at the end of the 2-week lead-in period, and control and intervention periods. The samples were analysed using high-throughput nuclear magnetic resonance (NMR) spectrometry for quantification of lipoprotein subclasses and particle sizes, cholesterol, glycerides, phospholipids, apolipoproteins, fatty acids, amino acids, ketone bodies, fluid balance, glycolysis and inflammation markers. Participants completed a 3-day food diary at the end of the 2-week lead-in period, and control and intervention periods. Anthropometric measurements (height and weight) were measured at the same timepoints by a study nurse. Physical activity was instructed to be maintained at the pre-study level during the whole study period and it was monitored by using a 3-axial accelerometer (Active style Pro HJA, Omron, Japan). Cognition was measured with standardized neuropsychological tests (Bourdon-Wiersma, FAT, N-Back, NASA-TLX, KSS, RAVLT, Stroop, WMS-III, task-switching) under a psychologist's supervision and as tablet, PC or online tests. Brainfood reduced saturated fat and salt intakes and increased polyunsaturated fat, fibre, vitamin C and D, iron and magnesium intakes. Favourable effects were seen in the atherogenic lipid measurements, such as fatty acids, LDL, IDL and small VLDL, as well as fatty acids, phospholipids and glutamine. Intervention did not affect the physiological or cognitive parameters except for a decrease in inaccuracy of visual attention (p = 0.027). In conclusion, the Brainfood diet could be recommended for office workers as a healthy diet following Nordic nutrition recommendations.

Metabo groups in response to micronutrient intervention: Pilot study.

Micronutrients and their metabolites are cofactors in proteins involved in lipid metabolism. The present study was a subproject of the Harmonized Micronutrient Project (ClinTrials.gov # NCT01823744). Twenty participants were randomly selected from 136 children and adolescents that consumed a daily dose of 12 vitamins and 5 minerals supplementation for 6 weeks. The 20 individuals were divided into two pools of 10 individuals, according to their lipid profile at baseline (Pool 1 with lower triglycerides, LDL, and VLDL). The individuals were analyzed at baseline, after 6 weeks of daily supplementation, and after 6 weeks of a washout period in relation to anthropometric, body composition, food intake, lipid profile, micronutrient levels, and iTRAQ proteomic data. Genetic ancestry and its association with vitamin serum levels were also determined. After supplementation, LDL levels decreased while alpha‐tocopherol and pantothenic acid levels increased in pool 2; lipid profiles in pool 1 did not change but had higher plasma levels of pantothenic acid, pyridoxal, and pyridoxic acid. In pool 2, expression of some proteins increased, and expression of other ones decreased after intervention, while in pool 1, the same proteins responded inversely or did not change their levels. Plasma alpha‐tocopherol and Native American genetic ancestry explained a significant fraction of LDL plasma levels at baseline and in response to the intervention. After intervention, changes in expression of alpha‐1 antitrypsin, haptoglobin, Ig alpha‐1 chain C region, plasma protease C1 inhibitor, alpha‐1‐acid glycoprotein 1, fibrinogen alpha, beta, and gamma‐chain in individuals in pool 2 may be associated with levels of LDL and vitamin E. Vitamin E and Native American genetic ancestry may also be implicated in changes of vitamin E and LDL levels. The results of this pilot study must be validated in future studies with larger sample size or in in vitro studies.

Isolation and Characterization of metabolites from Clathria procera Ridley extract and Evaluation of its antidiabetic ef-fects in Streptozotocin-induced diabetic rats

Diabetes mellitus is a lethal metabolic disorder in humankind, which induce chronic complications. The present study investigated the effects of ethyl acetate extract from C. procera (EAE) and its isolates on antioxidant and in vitro antidiabetic activities, along with effects of EAE on plasma blood glucose concentrations in STZ-diabetic rats. For the first time, two known metabolites- N-((2S,3R,E)-1,3-dihydroxyoctadec-4-en-2-yl)stearamide (1) and N-((2S,3R,4E,8E)-1,3-dihydroxyoctadeca-4,8-dien-2-yl)palmitamide (2) are reported from EAE. 1, 2 and EAE depicted significant DPPH, superoxide free radicals, α-glucosidase and α-amylase inhibitory profile, indeed, 1 and 2 showed mild inhibitory profile against aldose reductase. In addition, the EAE (200 mg/kg b.w) revealed significant reduction in plasma glucose, body weight, total cholesterol, total glycerides and LDL levels in STZ-induced diabetic rats. The HDL levels were markedly augmented in EAE treated diabetic rats, when compared with control group. EAE abolished the increased lipid peroxidation in pancreas, liver and kidneys. The histopathological examination of pancreas of EAE protected the Langerhans islets with the number of islet cells were found statistically significant, when compared to diabetic control pancreas. Our data suggest that the C. procera has a potentiality to act against diabetes (both, in vitro and in vivo models) by inhibiting particularly digestive enzymes namely α-glucosidase and α-amylase, however further studies are required for proper establishment of mechanism of action and validating clinical effects.

Abstract 643: Integrated Systems Genetics Analysis of Tmem43 Mouse Model and Murine Genetic Reference Population of Bxd Strains Defines Novel Genetic Modifiers and Pathogenic Mechanisms in Arrhythmogenic Cardiomyopathy

Background: Arrhythmogenic cardiomyopathies (ACMs) are heritable diseases characterized by arrhythmias, related sudden death, fibro-fatty infiltration and progressive heart failure. Although the pathogenic variant p.S358L in TMEM43/ LUMA causes fully penetrant ACM (ARVC5) in patients, little in vivo evidence has been reported and the roles of Tmem43 in normal cardiac function and disease remain obscure and controversial. This study explored Tmem43-associated genetic modifiers using forward, reverse, and systems genetics analyses in vivo . Methods: Microarray of cardiac and jejunal tissues were performed in a newly created Tmem43 S358L knock-in mouse and in forty BXD strains, used as a murine genetic reference population (GRP). Levels of plasma and fecal lipids and Pparγ activities were defined in heart and jejunum of Tmem43 animals. Immunohistochemistry was performed in the myocardium of patients with non-TMEM43 origin ACM. Results: BXD strain cardiac tissues demonstrated high levels of Tmem43 expression that was significantly negatively correlated with heart mass and heart rate, while positively correlated with plasma HDL and LDL levels. Expression of Tmem43 was also significantly (r&gt;0.5, p&lt;0.00075) correlated with Ppargc1a ( Pcg1a ) in the heart and intestine of BXDs and Tmem43 mutants. In the Tmem43 S358L mouse heart, Tmem43 and Ppargc1a were downregulated resulting in reduced Pparγ activities. Conversely, Tmem43 and Ppars- regulated genes, including Mogat2, responsible for cholesterol, bile acid, and lipid absorption and re-esterification, were upregulated in the jejunum, resulting in elevated lipid absorption in the gut lumen and hyperlipidemia in Tmem43 S358L mutants. Expression of TMEM43 was disrupted in cardiomyocyte intercalated disks in ACM patients’ myocardium in contrast to normal controls. Conclusions: Tmem43 is an essential gene for cardiac and small intestine signaling and function. The S358L-Tmem43 pathogenic variant is significantly associated with downregulation of Tmem43 , Ppagc1a and Ppar γ in the myocardium and upregulation of Pparγ and Pparα signaling in small intestine in vivo . Testing plasma lipid levels and TMEM43 expression in ACM patients may provide critical information for personalized predictive care.

N-acetylcysteine with low-dose estrogen reduces cardiac ischemia-reperfusion injury.

Myocardial damage and mitochondrial dysfunction caused by cardiac ischemia-reperfusion (I/R) injury are intensified by endogenous estrogen deprivation. Although N-acetylcysteine (NAC) exerted cardioprotective effects, its benefits when used in combination with hormone therapy are unknown. We tested the hypothesis that a combination of NAC with low-dose estrogen improves cardiometabolic function and protects cardiac mitochondria against I/R injury, to a similar extent to regular-dose estrogen treatment, in estrogen-deprived rats. Female Wistar rats had a bilateral ovariectomy (OVX) or sham operation. Twelve weeks after the operation, OVX rats were treated with regular-dose estrogen (E; 50 µg/kg/day), low-dose estrogen (e; 25 µg/kg/day), NAC (N; 100 mg/kg/day) or combined low-dose estradiol with NAC (eN) for 4 weeks (n = 6/group). Metabolic parameters, echocardiography, heart rate variability and then cardiac I/R protocol involving 30-min coronary artery ligation, followed by 120-min reperfusion, were performed. OVX rats had increased body weight, visceral fat, fasting plasma glucose, HOMA-IR index, triglycerides, cholesterol and LDL levels (P < 0.05 vs sham). Only OVX-E and OVX-eN had a similarly improved HOMA-IR index. LVEF was increased in all treatment groups, but HRV was restored only by OVX-E and OVX-eN. After I/R, myocardial infarct size was decreased in both OVX-E and OVX-eN groups. OVX-E and OVX-eN rats similarly had a reduced mitochondrial ROS level and increased mitochondrial membrane potential in the ischemic myocardium. In conclusion, combined NAC with low-dose estrogen and regular-dose estrogen therapy similarly improve cardiometabolic function, prevent cardiac mitochondrial dysfunction and reduces the infarct size in estrogen-deprived rats with cardiac I/R injury.

Correlation of serum uric acid levels with traditional risk factors and cardiovascular disease in the area of Blida (Algeria)

To investigate the relationship of Serum Uric Acid (SUA) levels with the traditional risk factors and fatal cardiovascular disease (CVD) in the area of Blida (Algeria). We prospectively enrolled 1954 hypertensive patients: 912 men (57.4 ± 8.5 years old) and 1042 women (56.3 ± 8.7 years old) consulting for evaluation in our hypertension clinic. In all subjects; routine blood chemistry, including SUA determination, echocardiographic examination, office and 24 h ambulatory blood pressure (BP) monitoring were obtained along with data regarding lifestyle habits. The risk of fatal cardiovascular disease was evaluated by using the SCORE risk chart for countries with low CVD risk based on the following risk factors: age, sex, smoking, systolic BP and total cholesterol. Spearman analysis showed that the SUA levels were significantly and positively associated with the average 24 hours systolic BP levels (RS = 0.088, P < 0.02 for SBP) but not with diastolic BP levels (RS = 0.051, P > 0.05). Furthermore, the Kruskal Wallis analysis revealed that SUA levels were significantly associated with fatal CVD risk ( P < 0.01). Specifically, patients with SCORE risk < 1%, between 1–5%, risk > 5% had SUA levels of 5.3 ± 1.1 mg/dl, 5.9 ± 1.3 mg/dl and 6.7 ± 1.7 mg/dl respectively (Z:- 6.9 P< 0.001). SUA levels were significantly associated with almost all major risk factors. Specifically SUA levels were significantly higher in males (Mann-Whitney U = 17384.70, P < 0.01), in elder patients (RS = 0.12, P < 0.01), in patients with increased body mass index (RS = 0.381, P < 0.01), with diabetes (U = 17745.70, P < 0.05) and with increased systolic BP levels (RS = 0.087, P < 0.04). In contrast, smoking status was not related with SUA levels ( P = NS). Regarding lipoproteins, only serum HDL levels were significantly associated with SUA levels (RS= – 0.327, P < 0.01) but not total cholesterol and LDL plasma levels (NS). Subjects with lower SUA levels presented lower BP levels as well as SCORE risk for fatal cardiovascular disease. SUA levels were significantly associated with SBP levels. The relative importance of these associations has made it possible to specify the possible role of uric acid in the cardiovascular continuum.