Plasma Very Low Density Lipoprotein Research Articles

Review of the efficacy and safety of PCSK9 inhibitors in the therapy of lipid metabolism disorders

Lipid metabolism disorder with a predominance of very-low-density lipoproteins (VLDL), triglycerides (TG), and cholesterol (CS) in the blood plasma contributes to the development of atherosclerotic diseases, which to date remain the main cause of death among the population, ranking first among all causes of death in the world and claiming the lives of 4 million Earth inhabitants every year. In this regard, there is a need to search for drugs that reduce the level of cholesterol, triglycerides, and VLDL in blood plasma. Such a group of drugs is PCSK9 inhibitors. Purpose of the study: to evaluate the efficacy and safety of the new class of lipid-lowering drugs — PCSK9 inhibitors.

Application of enzymatic fluorometric assays to quantify phosphatidylcholine, phosphatidylethanolamine and sphingomyelin in human plasma lipoproteins

Phosphatidylcholine (PC), phosphatidylethanolamine (PE) and sphingomyelin (SM) are important surface components of plasma lipoproteins, including very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL) and high-density lipoproteins (HDL). However, the pathophysiological roles of PC, PE and SM in lipoproteins have not been well characterized owing to the difficulties in quantifying phospholipid classes in lipoproteins. In this study, we assessed the precision and accuracy of the enzymatic fluorometric assays for measuring PC, PE and SM in VLDL, LDL and HDL, which were isolated from human plasma by ultracentrifugation. The within-run coefficients of variation (CV) for the measurements of PC, PE and SM in lipoproteins were 1.5–2.8 %, 1.1–2.4 % and 0.9–2.3 %, respectively, whereas the between-run CVs for the PC, PE and SM assays were 2.7–4.7 %, 2.1–4.5 % and 1.6–3.3 %, respectively. Excellent linearity and almost complete recovery were achieved for all assays measuring PC, PE and SM in VLDL, LDL and HDL. Our preliminary results using these enzymatic fluorometric assays suggested that the phospholipid compositions were different among VLDL, LDL and HDL. In conclusion, we established high-throughput enzymatic fluorometric assays to quantify PC, PE and SM in human plasma VLDL, LDL and HDL, which will be useful for further investigation of pathophysiological roles of phospholipids in lipoproteins.

Omega 3 Improves Both apoB100-containing Lipoprotein Turnover and their Sphingolipid Profile in Hypertriglyceridemia.

Evidence for an association between sphingolipids and metabolic disorders is increasingly reported. Omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) improve apolipoprotein B100 (apoB100)-containing lipoprotein metabolism, but their effects on the sphingolipid content in lipoproteins remain unknown. In subjects with hypertriglyceridemia, we analyzed the effect of n-3 LC-PUFAs on the turnover apoB100-containing lipoproteins and on their sphingolipid content and looked for the possible association between these lipid levels and apoB100-containing lipoprotein turnover parameters. Six subjects underwent a kinetic study before and after n-3 supplementation for 2 months with 1 g of fish oil 3 times day containing 360 mg of eicosapentaenoic acid (EPA) and 240 mg of docosahexaenoic acid (DHA) in the form of triglycerides. We examined apoB100-containing lipoprotein turnover by primed perfusion labeled [5,5,5-2H3]-leucine and determined kinetic parameters using a multicompartmental model. We quantified sphingolipid species content in lipoproteins using mass spectrometry. Supplementation decreased very low-density lipoprotein (VLDL), triglyceride, and apoB100 concentrations. The VLDL neutral and polar lipids showed increased n-3 LC-PUFA and decreased n-6 LC-PUFA content. The conversion rate of VLDL1 to VLDL2 and of VLDL2 to LDL was increased. We measured a decrease in total apoB100 production and VLDL1 production. Supplementation reduced the total ceramide concentration in VLDL while the sphingomyelin content in LDL was increased. We found positive correlations between plasma palmitic acid and VLDL ceramide and between VLDL triglyceride and VLDL ceramide, and inverse correlations between VLDL n-3 LC-PUFA and VLDL production. Based on these results, we hypothesize that the improvement in apoB100 metabolism during n-3 LC-PUFA supplementation is contributed to by changes in sphingolipids.

The effect of acute intragastric vs. intravenous alcohol administration on inflammation markers, blood lipids and gallbladder motility in healthy men.

Ethanol intake increases plasma concentrations of triglycerides and chronic ethanol use impairs lipid metabolism and causes chronic inflammation. The gut plays an important role in metabolic handling of nutrients, including lipids, and a leaky gut associated with alcohol intake, allowing inflammatory signals to the portal vein, has been proposed to constitute a mechanism by which ethanol induces hepatic inflammation. We compared the effects of enteral and parenteral administration of ethanol on a range of circulating inflammation markers (including soluble CD163, a marker of liver macrophage activation), lipids, cholecystokinin (CCK) and fibroblast growth factor 19 (FGF19) as well as gallbladder volume. On two separate and randomized study days, we subjected healthy men (n=12) to double-blinded intragastric ethanol infusion (IGEI) and isoethanolemic intravenous ethanol infusion (IVEI). Blood was sampled and ultrasonographic evaluation of gallbladder volume was performed at frequent intervals for 4h after initiation of ethanol administration on both days. Little or no effects were observed on plasma levels of inflammation markers during IGEI and IVEI, respectively. Circulating levels of total, low-density lipoprotein and high-density lipoprotein cholesterol decreased after ethanol administration independently of the administration form. Triglyceride and very low-density lipoprotein (VLDL) cholesterol concentrations increased more after IGEI compared to IVEI. IVEI had no effect on plasma CCK and caused an increased gallbladder volume whereas IGEI elicited a CCK response (P<0.0001) without affecting gallbladder volume. Circulating FGF19 concentrations decreased equally in response to both ethanol administration forms. In conclusion, by evaluating a range of circulating inflammation markers during IGEI and IVEI we were not able to detect signs of systemic low-grade inflammation originating from the presence of ethanol in the gut. IVEI increased gallbladder volume whereas IGEI increased plasma CCK (with neutral effect on gallbladder volume), increased plasma VLDL cholesterol and triglyceride concentrations; indicating that the enteral route of administration may influence ethanol's effects on lipid metabolism.

Predictive value of plasma lipid levels for coronary artery disease (CAD)

Coronary artery disease (CAD) is a major cause of mortality and morbidity all over the world including Pakistan. CAD events are caused by the interplay of genetic and environmental factors, the effects of which are mainly mediated through cardiovascular risk factors. The major risk factors for CAD include hypertension, dyslipidemia, family history of premature atheroscleclerotic disease, obesity and sedentary lifestyle. However, it is clear from the existing literature that dyslipidemia plays a central role. This study was designed to examine the plasma lipid profile in coronary artery disease patients of both sexes receiving clinical care at various government hospitals in Lahore. Blood samples were collected from a total of 500 CAD patients and 250 healthy (control) subjects and subsequently analyzed for total cholesterol (TC), triglyceride (TG) and very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein cholesterol (HDL) levels. These measurements showed that TC, LDL, TG and VLDL levels were significantly elevated, whereas HDL levels were significantly reduced in CAD patients as compared to ethnically matched controls (p < 0.0001). However, lipid levels did not differ significantly between the male and female patients. Furthermore, the lipid profile parameters were strongly associated with CAD status and association of LDL/HDL remained significant even after making an adjustment for confounders. In addition, patients with comorbidities exhibited severe lipid abnormalities. In conclusion, this study revealed elevated plasma TG, TC, VLDL and LDL levels and attenuated plasma HDL levels in the Pakistani patients with coronary artery disease. Also, plasma lipid levels have the potential to serve as biomarkers for CAD in Pakistani population.

Plant-derived oleanolic acid ameliorates markers associated with non-alcoholic fatty liver disease in a diet-induced pre-diabetes rat model.

BackgroundThe increased prevalence of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus (T2DM) patients is becoming a worldwide health burden. Studies have indicated, however, that the onset of NAFLD occurs during pre-diabetes, a condition that often precedes the onset of T2DM. Oleanolic acid has been reported to improve glucose homeostasis in diet-induced pre-diabetes; however, the effects of this triterpene on liver function have not been evaluated.PurposeThis study was aimed at evaluating the therapeutic effects of oleanolic acid (OA) on selected markers of NAFLD in a pre-diabetes rat model.Methods and materialsPre-diabetes was induced by exposing Sprague Dawley rats to a high-fat high-carbohydrate diet for 20 weeks. The pre-diabetic rats were then treated with OA (80 mg/kg) or metformin (500 mg/kg) in the presence and absence of dietary interventions for a period of 12 weeks. The effects of OA were evaluated on parameters including plasma triglycerides (TGs), very low-density lipoprotein (VLDL) particles, bilirubin, AST, ALT, SREBP and antioxidant profile while the livers were collected for histological analysis.ResultsThe findings of this study showed that the administration of OA to pre-diabetic rats ameliorated body/liver weights ratio and significantly decreased plasma triglycerides (TGs) and VLDL. Furthermore, OA also ameliorated hepatic oxidative stress, lowered the SREBP expression and intrahepatic TGs. In addition, OA administration decreased plasma concentrations of bilirubin and liver damage enzyme biomarkers.ConclusionThe findings of the study suggest that OA ameliorates the risk of developing pre-diabetes-related NAFLD through the prevention of intrahepatic fat accumulation while also lowering hepatic inflammation.

Increased fat synthesis and limited apolipoprotein B cause lipid accumulation in the liver of broiler chickens exposed to chronic heat stress.

Chronic heat stress can enhance fat synthesis in broilers, and excessive triglyceride (TG) synthesized by the liver needs to be transported to extrahepatic tissues by very low density lipoprotein (VLDL) otherwise will accumulate in the liver, which may even result in hepatic steatosis. To investigate the molecular mechanisms by which chronic heat stress enhances fat synthesis and results in lipid accumulation in the liver of chickens, 144 broilers (Arbor Acres, 28-day-old) were randomly allocated to the normal control (NC, 22°C), heat stress (HS, consistent 32°C), or pair-fed (PF, 22°C) groups for a 14-D trial. The 7 D of heat exposure significantly increased the respiratory rate, relative weight of abdominal fat, the levels of glucose, TG, corticosterone, insulin, and VLDL in plasma, as well as the levels of TG, total cholesterol, acyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) in the liver, and mRNA expression levels of carbohydrate response element-binding protein (ChREBP), ACC, FAS, and microsomal triglyceride transfer protein (MTTP) in comparison with the other 2 groups. After 14 D of heat exposure, the relative weights of abdominal fat and liver and levels of TG and FAS in the liver were significantly higher in the HS group than in the other 2 groups, and there were no significant differences in the respiratory rate, plasma corticosterone concentration, apolipoprotein B (ApoB) level in the liver, and mRNA expression levels of key genes of fat synthesis among the 3 groups. In conclusion, chronic heat exposure activated LXRα pathway and enhanced fat synthesis in the liver after 7 D of heat exposure. After 14 D of heat exposure, heat-stressed broilers exhibited an adaptation to the high temperature in parameters of stress and fat synthesis gene expression levels. Moreover, chronic heat stress resulted in lipid accumulation in the liver of broilers, which is probably because the limited ApoB was not enough to transport the excessive TG synthesized by the liver in chronic heat-stressed broilers.

Genome-wide association study for plasma very low-density lipoprotein concentration in chicken.

The plasma very low-density lipoprotein (VLDL) concentration is an effective blood biochemical indicator that could be used to select lean chicken lines. In the current study, we used Genome-wide association study (GWAS) method to detect SNPs with significant effects on plasma VLDL concentration. As a result, 38 SNPs significantly associated with plasma VLDL concentration were identified using at least one of the three mixed linear model (MLM) packages, including GRAMMAR, EMMAX and GEMMA. Nearly, all these SNPs with significant effects on plasma VLDL concentration (except Gga_rs16160897) have significantly different allele frequencies between lean and fat lines. The 1-Mb regions surrounding these 38 SNPs were extracted, and twelve important regions were obtained after combining the overlaps. A total of 122 genes in these twelve important regions were detected. Among these genes, LRRK2, ABCD2, TLR4, E2F1, SUGP1, NCAN, KLF2 and RAB8A were identified as important genes for plasma VLDL concentration based on their basic functions. The results of this study may supply useful information to select lean chicken lines.

Association of Dyslipidemia, Oxidative Stress, and Inflammation With Redox Status in VLDL, LDL, and HDL Lipoproteins in Patients With Renal Disease.

Some cardiovascular complications in patients with chronic kidney disease and end-stage renal disease may be caused by structurally and functionally modified lipoproteins. Redox status (advanced oxidation protein products [AOPPs]), prooxidant-antioxidant balance, total protein sulfhydryl (SH-groups), and paraoxonase 1 (PON1) activity were assessed in 77 renal patients and 20 controls. Lipoproteins were isolated using ultracentrifugation. PON1, PON3, and pentraxin-3 concentration were determined by enzyme-linked immunosorbent assay (ELISA). Dyslipidemia-Oxy-Inflammation (DOI) score was calculated as a sum of dyslipidemia, oxidative stress, and inflammation scores. The dyslipidemia score ( P < .001), oxy score ( P < .01), inflammation score (P < .001), and the DOI score ( P < .001) were higher in patient groups compared with controls. The very-low-density lipoprotein (VLDL) fraction contained the highest amount of AOPP ( P < .001) compared with other lipoprotein fractions in all groups. The low-density lipoprotein (LDL) fraction contained elevated AOPP in all groups compared with the high-density lipoprotein (HDL) fraction ( P < .001). Significant positive correlation was observed between AOPP in LDL fraction and DOI score (ρ = 0.510, P < .01). Dyslipidemia, oxidative stress, and inflammation play an interactive role in renal disease and are mutually associated with redox status in VLDL, LDL, and HDL lipoproteins in plasma of renal patients.

The Antioxidant Status and Biochemical Parameters in Kid Goats Naturally Infected with Peste Des Petits Ruminants Virus

Background: Peste des petits ruminants (PPR) is an acute and highly contagious viral disease of small ruminants. The disease is high economical importance because of the high mortality rate. Oxidative stress is an active field of research in small ruminant medicine and has been implicated in numerous disease processes including sepsis, mastitis, acidosis, enteritis, pneumonia, respiratory, and joint diseases. Compared to human medicine, only a limited number of conditions have been investigated in regard to the effects of oxidative stress in small ruminants. The aim of this study was to determined and compared the oxidative status and some biochemical parameters in kid goats with PPR.Materials, Methods &amp; Results: The study was performed on 15 healthy hair of kid goats (control group) and 15 kids naturally infected with Peste des Petits Ruminants (PPR). Competitive enzyme linked immunosorbent assay (C-ELISA) was used for serological detection of PPRV specific antibodies, and a reverse transcription polymerase chain reaction (RT-PCR) was performed for the detection of PPR virus. Concentrations of plasma biochemical parameters were analysed by a clinical chemistry analyser, and blood biochemical indices determined, including total protein, albumin, alkaline phosphatase (ALP), aspartate amino transferase (AST), γ- glutamyl transferase (GGT), lactate dehydrogenase (LDH), glucose, very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL). The plasma CAT activity, plasma GSHPx activity and plasma lipid peroxidation level was measured according to the specific methods. Besides, vitamin C values were colorimetrically determined using a phosphotungustic method acid method and vitamin E values were determined spectrophotometrically method. Plasma MDA concentrations were markedly increased in the group of kid goats with PPR (P &lt; 0.001) whereas GSHPx (P &lt; 0.01), and CAT (P &lt; 0.01) activities were significantly depressed as well as concentrations of vitamins E (P &lt; 0.05) and vitamin C (P &lt; 0.001). Significant differences between groups were showed relative to plasma total protein (P &lt; 0.05), albumin (P &lt; 0.05), ALP (P &lt; 0.05), AST (P &lt; 0.01), GGT (P &lt; 0.05), LDH (P &lt; 0.05), glucose (P &lt; 0.001), VLDL (P &lt; 0.05), LDL (P &lt; 0.01), and HDL (P &lt; 0.05)Discussion: The clinical and postmortem findings of PPRV infection may be sufficient for the diagnosis in the endemic areas, yet labaratory confirmation is essential for definitive diagnosis because of the clinical similarity of PPR to rinderpest. In this study used both C-ELISA and RT-PCR in the diagnosis of suspected disease. The decrease level of VLDL, LDL, and HDL in the kids with PPR were consistent findings with liver damage, and the cause of decrease could be inadequate synthesis of cholesterol that main structure of lipoproteins due to liver dysfunction. Plasma MDA concentrations were found to be increased in the kid goats with PPR compared to the control group, while decreases of GSHPx and CAT activities were observed. Because of GSHPx and CAT are involved in the conversion of radicals into less effective metabolites, these changes coupled to the increase of MDA concentrations, suggest that an excessive ROS production occurred during PPR infection. This study has highlighted the occurrence of an oxidative stress with important differences in antioxidant status as reflected by assessment of some enzymatic and non-enzymatic antioxidants in kids infected by PPRV. In conclusion, this study has highlighted the occurrence of an oxidative stress with important differences in antioxidant status as reflected by assessment of some enzymatic and non-enzymatic antioxidants in kids infected by PPRV. Furthermore, the liver was effected by PPRV infection.

DGAT2 Inhibition Alters Aspects of Triglyceride Metabolism in Rodents but Not in Non-human Primates

Diacylglycerol acyltransferase 2 (DGAT2) catalyzes the final step in triglyceride (TG) synthesis and has been shown to play a role in regulating hepatic very-low-density lipoprotein (VLDL) production in rodents. To explore the potential of DGAT2 as a therapeutic target for the treatment of dyslipidemia, we tested the effects of small-molecule inhibitors and gene silencing both invitro and invivo. Consistent with prior reports, chronic inhibition of DGAT2 in amurine model of obesity led to correction of multiple lipid parameters. In contrast, experiments in primary human, rhesus, and cynomolgus hepatocytes demonstrated that selective inhibition of DGAT2 has only a modest effect. Acute and chronic inhibition of DGAT2 in rhesus primates recapitulated the invitro data yielding no significant effects on production of plasma TG or VLDL apolipoprotein B. These results call into question whether selective inhibition of DGAT2 is sufficient for remediation of dyslipidemia.

Effects of dietary xylooligosaccharides on the performance, egg quality, nutrient digestibility and plasma parameters of laying hens

This study was conducted to determine the effects of dietary supplementation with xylooligosaccharides (XOS) on the laying performance, egg quality, nutrient digestibility and plasma parameters of Lohmann hens. A total of 1080 Lohmann laying hens (28 weeks of age) were assigned to six treatment diets that included XOS at concentrations of 0, 0.1, 0.2, 0.3, 0.4 or 0.5g/kg for 8 weeks. Each treatment had six replicates with 10 cages (3 birds/cage). Egg production, egg weight and feed intake were recorded daily. Egg quality traits were recorded every 4 weeks. Plasma parameters were evaluated, and a metabolic experiment using 36 birds from each replicate was conducted at the end of the study. The results show that XOS supplementation had no effect on the production performance but could significantly improve the quality of the eggshell; eggshell thickness and eggshell relative weight showed a linear or quadratic response to increasing dietary XOS (P<0.05). However, XOS supplementation did not influence other egg quality characteristics, such as yolk relative weight, Haugh unit, yolk color and shell strength. On the other hand, XOS supplementation could significantly increase the apparent digestibility of the calcium (P<0.05). Moreover, plasma glutamic–pyruvic transaminase (GPT), cholesterol, high-density lipoprotein (HDL), and very low-density lipoprotein (VLDL) decreased linearly (P<0.05) with the increasing dietary XOS concentration. XOS can be concluded to be an effective feed additive because it improves the quality of the eggshell by increasing the apparent digestibility of calcium and because it decreases the plasma GPT, cholesterol, HDL, and VLDL of laying hens.

Exercise Training Reduces Liver Fat and Increases Rates of VLDL Clearance But Not VLDL Production in NAFLD.

Randomized controlled trials in nonalcoholic fatty liver disease (NAFLD) have shown that regular exercise, even without calorie restriction, reduces liver steatosis. A previous study has shown that 16 weeks of supervised exercise training in NAFLD did not affect total very low-density lipoprotein (VLDL) kinetics. The objective of the study was to determine the effect of exercise training on intrahepatocellular fat (IHCL) and the kinetics of large triglyceride (TG)-rich VLDL1 and smaller denser VLDL2, which has a lower TG content. This was a 16-week randomized controlled trial. A total of 27 sedentary patients with NAFLD participated in the trial. The intervention was composed of supervised exercise with moderate-intensity aerobic exercise or conventional lifestyle advice (control). VLDL1 and VLDL2-TG and apolipoprotein B (apoB) kinetics were investigated using stable isotopes before and after the intervention. In the exercise group, maximal oxygen uptake increased by 31% ± 6% (mean ± SEM) and IHCL decreased from 19.6% (14.8%, 30.0%) to 8.9% (5.4%, 17.3%) (median [interquartile range]) with no significant change in maximal oxygen uptake or IHCL in the control group (change between groups, P < .001 and P = .02, respectively). Exercise training increased VLDL1-TG and apoB fractional catabolic rates, a measure of clearance, (change between groups, P = .02 and P = .01, respectively), and VLDL1-apoB production rate (change between groups, P = .006), with no change in VLDL1-TG production rate. Plasma TG did not change in either group. An increased clearance of VLDL1 may contribute to the significant decrease in liver fat after 16 weeks of exercise in NAFLD. A longer duration or higher-intensity exercise interventions may be needed to lower the plasma TG and VLDL production rate.

Comparison of the DASH (Dietary Approaches to Stop Hypertension) diet and a higher-fat DASH diet on blood pressure and lipids and lipoproteins: a randomized controlled trial1–3

Background: The DASH (Dietary Approaches to Stop Hypertension) dietary pattern, which is high in fruit, vegetables, and low-fat dairy foods, significantly lowers blood pressure as well as low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol.Objective: The study was designed to test the effects of substituting full-fat for low-fat dairy foods in the DASH diet, with a corresponding increase in fat and a reduction in sugar intake, on blood pressure and plasma lipids and lipoproteins.Design: This was a 3-period randomized crossover trial in free-living healthy individuals who consumed in random order a control diet, a standard DASH diet, and a higher-fat, lower-carbohydrate modification of the DASH diet (HF-DASH diet) for 3 wk each, separated by 2-wk washout periods. Laboratory measurements, which included lipoprotein particle concentrations determined by ion mobility, were made at the end of each experimental diet.Results: Thirty-six participants completed all 3 dietary periods. Blood pressure was reduced similarly with the DASH and HF-DASH diets compared with the control diet. The HF-DASH diet significantly reduced triglycerides and large and medium very-low-density lipoprotein (VLDL) particle concentrations and increased LDL peak particle diameter compared with the DASH diet. The DASH diet, but not the HF-DASH diet, significantly reduced LDL cholesterol, HDL cholesterol, apolipoprotein A-I, intermediate-density lipoprotein and large LDL particles, and LDL peak diameter compared with the control diet.Conclusions: The HF-DASH diet lowered blood pressure to the same extent as the DASH diet but also reduced plasma triglyceride and VLDL concentrations without significantly increasing LDL cholesterol. This trial was registered at clinicaltrials.gov as NCT01404897.

Down Regulation of Atrial Gap Junction in Metabolic Syndrome is Associated with VLDL-Induced O-Linked Glycosylation

Background: The prevalence ofatrial fibrillation (AF) increased in patients with the metabolic syndrome (MetS) compared with the general population. MetS is often accompanied with very-low-density lipoprotein (VLDL) elevation, we examined whether VLDL, isolated from MetS patients, may adversely affect the physiology of gap junction as an underlying mechanism of AF.Methods and Results: Pooled plasma VLDL was isolated from normal and MetS individuals. Wild type C57BL/6 male mice were divided into 3 groups to receive tail-vein injections of saline (Control), normal-VLDL (N-VLDL, 15 µg/g) or MetS-VLDL (MetS-VLDL, 15 µg/g) three times/week for 6 consecutive weeks. After eletrocardiography recordings, hearts were harvested for RNA using quantitative RT-PCR and tissue histology. Compared with Control, MetS-VLDL significantly retarded atrial conduction (widening P wave of electrocardiography 30.2±4.3 ms vs 38.8±5.8 ms, P=0.0187, and PR prolongation 49.4±10.9 ms vs 72.2±17.3 ms, P=0.0224; n=5), but N-VLDL did not. MetS-VLDL also significantly reduced gap junction GJA5 mRNA from the Control value of 1.00±0.68 (folds to control in AU) to 0.53±0.14 (P=0.01; n=6); the changes induced by N-VLDL (1.64±0.68) were not significant. Immunohistologic analysis confirmed reduction of the GJA5 protein connexin 40 (Cx40) in atrial tissues. Immunoprecipitation showed O-GlcNAc-Cx40 in MetS-VLDL-treated atrial myocytes. Conclusions: The VLDL-induced morphological (gap junction) and electrophysiological (atrial conduction) disturbances may explain the increased prevalence of AF in MetS. This study strongly suggests VLDL as a treatment target in MetS.

Effect of pre-partum supplementation of rumen protected methionine plus lysine and choline on the performance of crossbred cows

The study was conducted to determine rumen escape potential (REP) of commercial rumen protected methionine (RPM), lysine (RPL) and choline (RPC) products and to examine the effect of supplementing RPM plus RPL and RPC on the performance of preparturient crossbred cows. Crossbred cows (27; 2nd to 4th lactation) were randomly assigned to 3 groups of 9 animals each, on the basis of most probable production ability (MPPA). Cows in control group (T1), were fed basal diet as per NRC (2001). The cows in second group (T2), were supplemented with 5 g RPM and 20 g RPL, and those in third group (T3), were fed 54 g RPC per cow/day for 40 days pre-partum. In sacco study revealed that REP of RPM, RPL and RPC was 75.20, 54.97 and 72.89%, respectively. Supplementation of RPM plus RPL and RPC resulted in higher body condition score (BCS) in crossbred cows on the day of parturition. Nutrient intake was similar among the groups, except that duodenal supply of methionine and lysine was higher in T2 group. Plasma triglycerides, VLDL (very low density lipoproteins) and phosphatidylcholine levels were higher in T2 and T3 groups while vitamin E level was higher in T3 group, on the day of parturition, indicating better immune status. It was concluded that fortification of ration with RPM plus RPL and RPC resulted in improved body condition score, duodenal supply of methionine and lysine and better immune status in cows during prepartum period.

Lipid Profiles are Altered in Rats Fed with Different Garlic Cultivars

Garlic has antioxidant and hypocholesterolemic properties that are attributed to its organosulfur compounds being allicin, which is reported to be the most active of these compounds. We hypothesized that allicin content could reduce plasma concentrations of triglycerides (TG), total cholesterol (TC), HDL (high density lipoproteins), VLDL (very low density lipoproteins), and glucose. Two different cultivars of commercial garlic, Peruano and Jinxiang, were used. Thirty male Wistar rats were distributed into 6 groups and fed for 15 days with standard diet (Control), Control with Peruano garlic treatment (CGP), Control with Jinxiang garlic treatment (CGCH), cholesterol-added control diet (CholC), cholesterol-added diet with Peruano garlic treatment (CholGP), and cholesterol-added diet with Jinxiang garlic treatment (CholGCH). Garlic treatment consisted of a daily oral dose of 1ml of lyophilized garlic. We observed that garlic treatment in Control group significantly reduced plasma TG and VLDL concentrations. The CGCH group presented a significant increase in plasma TC levels (25.5%) and glucose (11%). No significant changes in TC, HDL, TG and VLDL were observed in CholGP and CholGCH, but levels of fasting plasma glucose were increased: CholGP (23%) and CholGCH (27.5%). Results suggested allicin treatments alter lipid profile in rats. Nevertheless, further studies are necessary to address the increase in plasma glucose levels. (Int J Biomed. 2015;5(3):155-161.)

Effect of apolipoprotein C3 genetic polymorphisms on serum lipid levels and the risk of intracerebral hemorrhage.

BackgroundSerum lipid levels are associated with the risk of intracerebral hemorrhage (ICH). Genetic variants in the apolipoprotein C3 (APOC3) gene were associated with plasma triglyceride (TG) and very-low-density lipoprotein (VLDL) levels. The aim of this study was to evaluate the effect of two genetic variants (1100 C/T and 3238 C/G) of APOC3 on serum lipid levels and risk of ICH.MethodsA prospective hospital-based case–control design and logistic regression analysis were utilized. We enrolled 150 ICH patients and 150 age- and gender-matched controls. The APOC3 gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).ResultsICH patients had a significantly higher frequency of APOC3 3238 GG genotype [odds ratio (OR) =2.97, 95 % confidence interval (CI) = 1.20, 7.38; P = 0.02] and APOC3 3238 G allele (OR =1.53, 95 % CI = 1.03, 2.27; P = 0.04) than controls. The APOC3 3238 G allele was significantly associated with increasing plasma TG levels and VLDL levels both in ICH cases (P = 0.01) and controls (P = 0.02). No association was found between APOC3 1100 C/T polymorphisms and ICH.ConclusionTo the best of our knowledge, this is the first report in the literature that the APOC3 3238 GG genotype and G allele might contribute to an increased risk of ICH as a result of its effect on serum lipid levels.

Three novel single nucleotide polymorphisms of the 3-hydroxy-3-methylglutaryl coenzyme A reductase gene associated with egg-production in chicken.

Different single-strand conformation polymorphism (SSCP) patterns of the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) gene amplified by six pairs of primers were sequenced. Comparisons among the six nucleotide sequences of three genotypes revealed three base substitutions (G-789-A, C-937-G, and A-2316-C) in the HMGCR gene. The genotypes of single nucleotide polymorphism 1 (SNP1) and SNP3 were significantly associated with the number of eggs (P < 0.01), and the different genotypes of SNP2 did not significantly influence the number of eggs. The genotypes of all three SNPs were not related to the hatching rate of fertilized eggs (P > 0.05). Of the three SNPs of the HMGCR gene, those genotypes with lower plasma very low-density lipoprotein (VLDL) concentrations had higher egg production. The 300-day egg production of the six studied haplotypes showed three levels (P < 0.01). The ADE and ACE haplotypes showed lower egg production than the other haplotypes. The ADE haplotype had the highest plasma VLDL concentration, and the ACE haplotype had the lowest plasma VLDL concentration. We concluded that specific variants of the HMGCR gene are associated with chicken egg production, and haplotypes with higher and lower plasma VLDL concentrations showed lower egg production than other haplotypes.

Diets naturally rich in polyphenols improve fasting and postprandial dyslipidemia and reduce oxidative stress: a randomized controlled trial

The postprandial triglyceride-rich lipoprotein (TRL) concentration is a recognized independent cardiovascular disease risk factor. Diet is the natural approach for these postprandial alterations. Dietary polyphenols and long chain n-3 polyunsaturated fatty acids (LCn3s) are associated with a lower cardiovascular disease risk. This randomized controlled study evaluated, in persons with a high risk of cardiovascular disease, the effects of diets naturally rich in polyphenols and/or marine LCn3s on plasma TRLs and urinary 8-isoprostane concentrations, a biomarker of oxidative stress. According to a 2 × 2 factorial design, 86 overweight/obese individuals with a large waist circumference and any other component of the metabolic syndrome were randomly assigned to an isoenergetic diet 1) poor in LCn3s and polyphenols, 2) rich in LCn3s, 3) rich in polyphenols, or 4) rich in LCn3s and polyphenols. The diets were similar in all other components. Before and after the 8-wk intervention, fasting and postmeal TRLs and 8-isoprostane concentrations in 24-h urine samples were measured. Dietary adherence was good in all participants. Polyphenols significantly reduced fasting triglyceride concentrations (2-factor ANOVA) in plasma (P = 0.023) and large very-low-density lipoproteins (VLDLs) (P = 0.016) and postprandial triglyceride total area under the curve in plasma (P = 0.041) and large VLDLs (P = 0.004). LCn3s reduced postprandial chylomicron cholesterol and VLDL apolipoprotein B-48. The concentrations of urinary 8-isoprostane decreased significantly with the polyphenol-rich diets. Lipoprotein changes induced by the intervention significantly correlated with changes in 8-isoprostane. Diets naturally rich in polyphenols positively influence fasting and postprandial TRLs and reduce oxidative stress. Marine LCn3s reduce TRLs of exogenous origin. Through their effects on postprandial lipemia and oxidative stress, polyphenols may favorably affect cardiovascular disease risk.