Serum High-density Lipoprotein Cholesterol Concentrations Research Articles

Antisense Oligonucleotides in Dyslipidemia Management: A Review of Clinical Trials.

Elevated serum total cholesterol levels, very low-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, or a decreased serum high-density lipoprotein cholesterol concentration characterize dyslipidemia. Antisense Oligonucleotide therapy in dyslipidemia targets apolipoprotein B (ApoB), an essential component of low-density lipoprotein (LDL) associated with atherosclerosis development. This review aims to critically evaluate the efficacy and safety of this group of medications in mitigating dyslipidemia in at-risk individuals and its potential role in advancing personalized medicine in the management of dyslipidemias. A detailed search was conducted from multiple databases adhering to the PRISMA guidelines. Clinical trials and randomized controlled trials on antisense oligonucleotides for management of dyslipidemias were included, excluding non-English studies, case reports and all forms of reviews. Data was screened, with duplicates removed, and key findings were synthesized using a narrative approach. The potential of antisense oligonucleotides (ASOs) to treat dyslipidemia and other disorders has attracted much interest. Several studies and clinical trials have been conducted on the safety and tolerability of ASOs for dyslipidemia. Although statins are the mainstay management of hypercholesterolemia, there is evidence from clinical trials that ASOs can even be more effective with little to no side effects. Novel therapeutic approaches such as antisense oligonucleotides (ASOs) offer tailored therapeutic alternatives. ASOs such as Mipomersen and Volanesorsen provide additional treatment options for patients with inherited lipid abnormalities by lowering certain atherogenic lipoproteins such as apo B and ApoC-III, respectively.

Biomolecules of Adipose Tissue in Atherosclerotic Plaques of Men With Coronary Atherosclerosis.

To study metabolic molecules (adiponectin, adipsin, resistin, glucagon-like peptide-1 (GLP-1), glucagon, secretin) of adipose tissue in atherosclerotic plaques (AP) and their associations with AP instability in men with coronary atherosclerosis. Metabolic molecules (adipocytokines and metabolic hormones) of adipose tissue can act as enzymes, hormones or growth factors in modulating insulin resistance and lipid and glucose metabolism and indirectly influence the course of the atherosclerotic process. This study included 48 men from whom 139 coronary artery (CA) samples were collected during coronary artery bypass grafting, after obtaining the informed consent. According to the histological conclusion, 84 (60.4%) CA plaques were stable, 44 (31.7%) were unstable, and 11 histological samples had a conditionally unchanged CA intima (7.9%). The concentrations of adiponectin, adipsin, resistin, GLP-1, glucagon, and secretin were measured in AP homogenates by multiplex analysis using the Human Metabolic Hormone V3 panel (MILLIPLEX, Germany). During the study, demographic and anthropometric characteristics, medical history, and presence of chronic diseases were recorded. The glucagon concentration in the conditionally unchanged intima was 16.7% lower and in the fragments of unstable atherosclerotic plaques 41.2% lower than in fragments of stable APs. However, the glucagon concentration in stable APs was 28% higher than in unstable APs. The secretin concentration in the conditionally unchanged intima was also lower than in stable APs by 41.2%, while in stable APs, the secretin concentration was 20% higher than in unstable APs. The adiponectin concentrations were directly correlated with serum high-density lipoprotein cholesterol (HDL-C) concentrations (r=0.286; p=0.002), while the secretin concentrations were inversely correlated with serum HDL-C concentrations (r= -0.199; p=0.038). The probability of having an unstable AP (in relation to conditionally unchanged intima) increases by 35.8% with an increase in the AP glucagon concentration by 1 pg/mg protein. The probability of having a stable AP (in relation to unchanged intima) increases by 29.4% with an increase in the AP glucagon concentration by 1 pg/mg protein and by 10.1% with an increase in the AP secretin concentration by 1 pg/mg protein. The AP adiponectin concentration directly correlates and the AP secretin concentration inversely correlates with the serum concentration of HDL-C. The presence of both stable and unstable APs is directly associated with the AP glucagon concentration in men with coronary atherosclerosis. The AP secretin concentration is directly associated with plaque stability in men with coronary atherosclerosis. Further thorough study of the identified markers in atherosclerotic lesions will allow using them as potential targets for therapy.

Assessment of leukocyte and systemic inflammation index ratios in dyslipidemia patients with dry eye disease: a retrospective case‒control study

BackgroundDry eye disease (DED) is a complication of dyslipidemia (DLP) that is caused by metabolic syndrome and increased inflammation. This research aimed to assess leukocyte and systemic inflammation index ratios as potential biomarkers for systemic inflammation in dyslipidemia patients with dry eye disease (DLP-DED).MethodsSeveral blood biomarkers were studied in 32 patients with DLP-DED (study group) and 63 patients with DLP-only (control group). The evaluated blood biomarkers included specific systemic inflammation index ratios, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-lymphocyte and platelet ratio (NLPR), and lipid profiles, such as total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglyceride (TG), albumin (ALB), and C-reactive protein (CRP) levels.ResultsLymphocyte levels were significantly greater in the DLP-DED group than in the DLP-only group (P = 0.044). In addition, a significant negative correlation between HDL and the NLPR (P = 0.007; r= -0.428) and a significant negative correlation between the serum ALB concentration and the PLR (P = 0.008; r= -0.420) were identified as potential inflammatory predictors of DLP-DED.ConclusionThe findings of this study suggest that patients with DLP-DED may benefit from routine blood monitoring of their elevated lipid profile and blood inflammatory biomarkers, such as CRP, leukocytes, and systemic inflammation index ratios (NLR, PLR, MLR, and NLPR), to reduce the complications of DLP on ocular health. The correlation data suggest that the NLPR, PLR, serum ALB concentration, and serum HDL concentration may be valuable inflammatory biomarkers in DLP-DED patients. More research is required to ascertain the significance of the NLR, PLR, MLR, and NLPR and the additive role that leukocytes play.

Association between HDL cholesterol with diabetic retinopathy in diabetic patients: a cross-sectional retrospective study

ObjectiveDiabetic patients are often comorbid with dyslipidemia, however, the relationship between high-density lipoprotein cholesterol(HDL-C) and diabetic retinopathy (DR) in the adult diabetic population remains to be fully elucidated.The aim of this study is to evaluate the associations between HDL-C and DR in the United States adults with diabetes.MethodsA total of 1708 participants from the National Health and Nutrition Examination Survey (NHANES) 2005–2008 were enrolled in the present study. Fundus images of all study subjects were captured and evaluated using a digital camera and an ophthalmic digital imaging system, and the diagnosis of DR was made by the severity scale of the Early Treatment Diabetic Retinopathy Study (ETDRS).Roche Diagnostics were used to measure serum HDL-C concentration. The relationship of DR with HDL-C was investigated using multivariable logistic regression. The potential non-line correlation was explored with smooth curve fitting approach.ResultsThe fully-adjusted model showed that HDL-C positively correlated with DR(OR:1.69, 95%CI: 1.25–2.31).However, an inverted U-shaped association between them was observed by applying the smooth curve fitted method. The inflection point of HDL-C(1.99mmol/l) was calculated by utilizing the two-piecewise logistic regression model. In the subgroup analysis, the inverted U-shaped nonlinear correlation between HDL-C and DR was also found in female, Non-Hispanic White, and lower age groups.ConclusionOur study revealed an inverted U-shaped positive relationship between HDL-C and DR.The findings may provide us with a more comprehensive understanding of the association between HDL-C and DR.

Association of a genetic variant in angiopoietin-like 3 with serum HDL-C and risk of cardiovascular disease: A study of the MASHAD cohort over 6 years.

Loss-of-function (LOF) variants of the angiopoietin-like 3 (ANGPTL3) gene are reported to be associated with serum triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) concentrations and thereby affect the risk of cardiovascular disease (CVD). In the present study, we examined the association of rs10789117 in the ANGPTL 3 gene locus and the risk of CVD in the group of people who were part of the Mashhad-Stroke and Heart-Atherosclerotic-Disorders (MASHAD) cohort. One thousand and two healthy individuals enrolled in this study of whom 849 subjects were healthy and 153 subjects developed CVD outcomes after 6 years of follow-up. After a 12-h overnight fasting, 20 mL of blood samples were collected for the measurement of fasting blood glucose and lipid profile. DNA was extracted, and the Tetra-ARMS PCR (amplification refractory mutation system) was used for genotyping of rs10789117 in the ANGPTL3 gene. The genotype frequencies of the variant of rs10789117 in the ANGPTL3 gene were estimated using χ2 tests. Eventually, the statistical analysis was done by SPSS version 20. Individuals with AC/CC genotypes (rs10789117) were found to have to greater risk of CVD events compared to AA genotype (OR = 1.43, 95%CI = 1.01-2.02, p = 0.041). There was a 1.3-fold increase in cardiovascular events in individuals carrying the C allele of rs10789117 variant compared to non-carriers (OR = 1.32, 95%CI = 1.06-1.72, p value = 0.038). There were significant differences between different genotypes for serum triglyceride levels within the control group, but this difference was not significant in the group with CVD. Moreover, there was a significant association between CC genotype and CVD risk in the individuals with a normal serum HDL-C. We have found that a rs10789117 C>A in ANGPTL3 gene polymorphism was associated with incident CVD events, and this may be of value as a risk stratification biomarker in CVD in the Iranian population.

A four-week dietary intervention with mycoprotein-containing food products reduces serum cholesterol concentrations in community-dwelling, overweight adults: A randomised controlled trial

BackgroundSubstituting dietary meat and fish for mycoprotein, a fungal-derived food source rich in protein and fibre, decreases circulating cholesterol concentrations in laboratory-controlled studies. However, whether these findings can be translated to a home-based setting, and to decrease cholesterol concentrations in overweight and hypercholesterolemic individuals, remains to be established. ObjectiveWe investigated whether a remotely-delivered, home-based dietary intervention of mycoprotein-containing food products would affect various circulating cholesterol moieties and other markers of cardio-metabolic health in overweight (BMI >27.5 kg·m-2) and hypercholesterolaemic (>5.0 mmol·L-1) adults. MethodsSeventy-two participants were randomized into a controlled, parallel-group trial conducted in a free-living setting, in which they received home deliveries of either meat/fish control products (CON; n=39; BMI 33±1 kg·m-2; 13 males, 26 females) or mycoprotein-containing food products (MYC; n=33; BMI 32±1 kg·m-2; 13 males, 20 females) for 4 weeks. Fingertip blood samples were collected and sent via postal service before and after the dietary intervention period and analysed for concentrations of serum lipids, blood glucose and c-peptide. ResultsSerum total cholesterol concentrations were unchanged throughout the intervention in CON, but decreased by 5±2% in MYC (from 5.4±0.2 to 5.1±0.2 mmol·L-1; P<0.05). Serum low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol concentrations were also unchanged in CON, but decreased in MYC by 10±3% and 6±2% (both by 0.3±0.1 mmol·L-1; P<0.05). Serum high-density lipoprotein cholesterol and free triglyceride concentrations were unaffected in CON or MYC. Post-intervention, MYC displayed lower mean blood glucose (3.7±0.2 versus 4.3±0.2 mmol·L-1) and c-peptide (779±76 vs. 1064±86 pmol·L-1) concentrations (P<0.05) vs. CON. ConclusionsWe show that a home-based dietary intervention of mycoprotein-containing food products effectively lowers circulating cholesterol concentrations in overweight, hypercholesterolemic adults. This demonstrates that mycoprotein consumption is a feasible and ecologically valid dietary strategy to improve markers of cardio-metabolic health in an at-risk population under free living conditions. Clinical trial registrationNCT04773483 (https://classic.clinicaltrials.gov/ct2/show/NCT04773483)

Impacts of dietary lipids derived from animal or vegetable sources on healthy rats

ABSTRACT This study sought to assess the health impact of feeding adult healthy rats with either 7% (w/w) animal-derived fat (subcutaneous rump fat or peri-kidney fat) from domestic buffalo or vegetable oil (corn oil or olive oil) for 8 weeks on bioactivity; lipid profile; hepatic and cardiac histological changes. Twenty-four male albino rats were randomly categorized into four dietary groups (six rats/group): 1) diet contains 7% (w/w) corn oil; 2) diet contains 7% (w/w) olive oil; 3) diet contains 7% (w/w) subcutaneous rump fats and 4) diet contains 7% (w/w) Peri-kidney fats. Animal fats intake significantly increased serum total lipids (TL), triacylglycerol (TG), low-density lipoprotein cholesterol (LDLC), cardiac troponin-I (CTn-I) concentration as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), creatine kinase MB (CK-MB) and lactate dehydrogenase (LDH) activities compared to vegetable oils intake. In histopathological research, liver and heart sections excised from rats consumed animal-derived fats showed several signs of extensive damage, including inflammation as well as fibrosis. Compared to animal-derived fats, vegetable oils consumption markedly increased serum high-density lipoprotein cholesterol (HDLC) concentration and exhibited a potential attenuation effect on liver and heart enzymes activities and a potential role in the reduction of TG in the bloodstream of rats as well as revealed normal liver and heart histopathological architectures. In conclusion, this study suggests that, replacing animal fats, especially peri-kidney fat with vegetable oils, particularly olive oil in diets, liver and heart can be protected.

Effect of dyslipidemia, obesity, and atopic status on exhaled and alveolar nitric oxide in asthmatic children.

Dyslipidemia and obesity contribute to a pro-inflammatory state. Eosinophilic airway inflammation can be indirectly measured by fractional exhaled nitric oxide (FeNO) produced in the airways of asthmatic subjects. To compare exhaled nitric oxide (NO) and alveolar NO in asthmatic children with and without dyslipidemia. Asthmatic children (5-18 years old) had fasting serum low-density lipoprotein cholesterol, triglyceride, and high-density lipoprotein cholesterol (HDL-C) concentrations, and C-reactive protein (CRP) concentrations measured. FeNO was measured at constant flow rates of 20, 50, 100, and 300 ml/s by the chemiluminescence method. NO concentrations in tissue of the upper airways (CawNO) and the total flux of NO in the conducting airways (JawNO) were determined through FeNO at 20, 100, and 300 ml/s using a mathematical model. The atopic status was assessed using the skin prick test for aero-allergens. One hundred forty-one asthmatic children were enrolled with a mean (standard deviation) age of 11.82 (3.38) years. Sixty-four (45.4%) children had dyslipidemia and 20 (14.2%) were obese. Children with low HDL-C concentrations had significantly higher CawNO and JawNO than those with normal HDL-C concentrations (both p = 0.03). Asthmatic children with obesity had higher CRP concentrations than those with a normal weight (p < 0.001). Atopic children had a significantly higher FeNO, CawNO, and JawNO than non-atopic children (all p < 0.05). This study suggests an effect of HDL-C on CawNO and JawNO in asthmatic children. An intervention that normalizes HDL-C concentrations may be beneficial for airway inflammation in asthmatic children.

Evaluation of (sdLDLc*HCYc)/HDLc ratio in clinical auxiliary diagnosis of primary cerebral infarction

BackgroundTimely detection of cerebral infarction is of vital importance in planning intervention effect of rapid rehabilitation. The clinical auxiliary diagnosis value of single biomarker, including small dense low-density lipoprotein concentration (sdLDLc), homocysteine concentration (HCYc) and high-density lipoprotein cholesterol concentration (HDLc) for cerebral infarction has been confirmed by many studies. Whether the use of three biomarkers in combination by calculating (sdLDLc*HCYc)/HDLc ratio could improve the diagnosis ability for primary cerebral infarction remains to be unclear. In the present study, we conducted a cross-sectional study to evaluate the value of (sdLDLc*HCYc)/HDLc ratio in clinical auxiliary diagnosis of primary cerebral infarction.MethodsA total of 583 participants, including 299 healthy participants as control group and 284 participants diagnosed with first cerebral infarction as experiment group, were included in this respective study. The serum sdLDLc, HDLc and HCYc were measured by peroxidase method, enzyme‐linked immunosorbent assay and an enzymatic method, respectively.ResultsThe average concentration of sdLDL and HCY (0.69 ± 0.29 mmol/L and 18.14 ± 6.62 μmol/L) in experiment group was significantly higher than those in the control group (0.55 ± 0.22 mmol/L and 10.77 ± 2.67 μmol/L, P < 0.05). However, the average concentration of HDL (1.47 ± 0.25 mmol/L) in the control group was higher than that in the experiment group (1.33 ± 0.28 mmol/L, P < 0.05). Spearman correlation coefficient showed the three indicators are independent of each other. The positive predictive value of (sdLDLc*HCYc)/HDLc ratio (61.27%, 95% CI: 55.31–66.92) is higher than that in single biomarker (sdLDLc: 6.69 95% CI: 4.19–10.42, HCYc: 38.38%, 95% CI: 32.75–44.33, HDLc: 3.87%, 95% CI: 2.05–7.02). Receiver-operating characteristic curve (ROC) analysis illustrated that predictive power of (sdLDLc*HCYc)/HDLc was higher than single biomarker, including sdLDLc, HCYc and HDLc, in primary cerebral infarction.ConclusionsTherefore, (sdLDLc*HCYc)/HDLc ratio might be a better new indicator in clinical auxiliary diagnosis of primary cerebral infarction, which could be contributed to predicting cerebral infarction occurrence and provide a scientific basis for early prevention.

Limb-girdle muscular dystrophy type 2B causes HDL-C abnormalities in patients and statin-resistant muscle wasting in dysferlin-deficient mice

Limb-girdle muscular dystrophy (MD) type 2B (LGMD2B) and Duchenne MD (DMD) are caused by mutations to the Dysferlin and Dystrophin genes, respectively. We have recently demonstrated in typically mild dysferlin- and dystrophin-deficient mouse models that increased plasma cholesterol levels severely exacerbate muscle wasting, and that DMD patients display primary dyslipidemia characterized by elevated plasma cholesterol and triglycerides. Herein, we investigate lipoprotein abnormalities in LGMD2B and if statin therapy protects dysferlin-deficient mice (Dysf) from muscle damage. Herein, lipoproteins and liver enzymes from LGMD2B patients and dysferlin-null (Dysf) mice were analyzed. Simvastatin, which exhibits anti-muscle wasting effects in mouse models of DMD and corrects aberrant expression of key markers of lipid metabolism and endogenous cholesterol synthesis, was tested in Dysf mice. Muscle damage and fibrosis were assessed by immunohistochemistry and cholesterol signalling pathways via Western blot. LGMD2B patients show reduced serum high-density lipoprotein cholesterol (HDL-C) levels compared to healthy controls and exhibit a greater prevalence of abnormal total cholesterol (CHOL)/HDL-C ratios despite an absence of liver dysfunction. While Dysf mice presented with reduced CHOL and associated HDL-C and LDL-C-associated fractions, simvastatin treatment did not prevent muscle wasting in quadriceps and triceps muscle groups or correct aberrant low-density lipoprotein receptor (LDLR) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) protein expression. LGMD2B patients present with reduced serum concentrations of HDL-C, a major metabolic comorbidity, and as a result, statin therapy is unlikely to prevent muscle wasting in this population. We propose that like DMD, LGMD2B should be considered as a new type of genetic dyslipidemia.

Effects of pemafibrate on lipid metabolism in patients with type 2 diabetes and hypertriglyceridemia: A multi-center prospective observational study, the PARM-T2D study

AimsPemafibrate, a novel selective peroxisome proliferator-activated receptor modulator, was shown to ameliorate lipid abnormalities in a phase III clinical trial of patients with type 2 diabetes mellitus (T2DM). However, its efficacy has not been demonstrated in real-world clinical practice in patients with T2DM. MethodsWe performed a multi-center prospective observational study of the use of pemafibrate in patients with T2DM and hypertriglyceridemia versus conventional therapy, with or without a fibrate. The primary outcomes were the changes from baseline in fasting serum triglyceride (TG) and high-density lipoprotein-cholesterol (HDL-C) concentrations at week 52. ResultsWe recruited 650 patients, and data from 504 (252 per group) were analyzed after propensity score matching. In the pemafibrate group, both TG and HDL-C showed significant improvements (p < 0.001), and several indices reflecting TG-rich lipoproteins, low-density lipoprotein-cholesterol particle size, and liver enzyme elevations were significantly ameliorated compared with the control group, but there was no difference in glycemic control markers. One of the key secondary endpoints showed that switching from conventional fibrates to pemafibrate improved eGFR but increased uric acid concentration. ConclusionsIn patients with T2DM, pemafibrate has superior effects on lipid profile as well as liver and renal dysfunction to conventional fibrates.

Association of maternal HDL2-c concentration in the first trimester and the risk of large for gestational age birth

BackgroundMaternal lipid levels during pregnancy are critical for fetal development. Recent studies revealed that high-density lipoprotein cholesterol (HDL-c) levels during pregnancy were negatively correlated with birthweight. High-density lipoprotein 2 cholesterol (HDL2-c) is one of the major subclasses of HDL-c, and its relationship with birthweight is unclear. Association of HDL2-c concentration in the first trimester and risk of large for gestational age (LGA) was explored.MethodsThis study recruited pregnant women who registered in Fuxing Hospital from October 2018 to January 2020, had regular obstetric examinations during pregnancy, and delivered between June 2019 and September 2020. Finally, 549 participants were recruited for the study. Maternal demographic characteristics and venous blood were collected at the 6th-14th gestational week, and serum total cholesterol (TC), triglyceride (TG), HDL-c, HDL2-c, high-density lipoprotein 3 cholesterol (HDL3-c), and low-density lipoprotein cholesterol (LDL-c) concentrations were detected. Neonatal characteristics were collected at delivery. A logistic regression model was used to explore the relationship between the first trimester HDL2-c concentration and LGA incidence. A nomogram was developed, and the performance was evaluated with a concordance index.ResultsSeventy-five mothers delivered LGA infants, and the LGA incidence was 13.66%. LGA mothers had significantly lower serum HDL-c and HDL2-c concentrations than appropriate for gestational age (AGA) mothers. A logistic regression model showed that HDL2-c concentration was negatively correlated with LGA risk (odds ratio (OR) = 0.237, 95% confidence intervals (CI): 0.099–0.567, P = 0.001) when adjusted for age, prepregnancy body mass index (BMI), and parity. A nomogram was generated using all these risk factors. The area under the curve (AUC) was 0.663 (95% CI: 0.593–0.732).ConclusionsMaternal HDL2-c concentration in the first trimester was negatively correlated with the risk of LGA.

The Association Between Plasma Copper Concentration and Prevalence of Diabetes in Chinese Adults With Hypertension.

ObjectiveThe relationship between plasma copper concentration and prevalence of diabetes in adults with hypertension is unclear. We aimed to determine the association between plasma copper concentration and prevalence of diabetes in Chinese adults with hypertension.MethodsA total of 2,579 participants (697 cases and 1,882 controls) was included in this cross-sectional study. Plasma copper concentrations were determined by inductively coupled plasma mass spectrometry. Multivariable logistic regression model was used to determine the association between plasma copper concentration and prevalence of diabetes.ResultsAccording to the logistic regression analyses, the adjusted OR for the prevalence of diabetes in participants with plasma copper concentration ≥109.4 μg/dL was 1.26 (1.00, 1.58) compared with those with plasma copper concentration <109.4 μg/dL (P = 0.048). The association was no longer significant following further adjusting for serum high-density lipoprotein cholesterol (HDL-C) concentration as a potential confounder. Stratified analyses demonstrated that serum HDL-C concentration significantly modified the association between plasma copper concentration and prevalence of diabetes (P-interaction = 0.043). In the strata of serum HDL-C concentration ≥1.2 mmol/L, a 56% increased prevalence of diabetes was observed in participants with plasma copper concentration ≥109.4 μg/dL compared with those with plasma copper concentration <109.4 μg/dL (P = 0.008). No significant relationship between plasma copper concentration and prevalence of diabetes was found in other strata.ConclusionOur findings suggested that high plasma copper concentration (≥109.4 μg/dL) was associated with increased prevalence of diabetes in Chinese hypertensive adults with serum HDL-C concentration ≥1.2 mmol/L.

Inclusion of non-toxic sulfur in the diet positively affects daily growth, serum lipid profile and meat quality in finishing pigs

The present study investigated the effect of non-toxic sulfur (NTS) on the performance, lipid profile, and meat quality of finishing pigs. Ninety-days-old crossbred castrated male pigs [Duroc x (Yorkshire × Landrace)] with an average body weight (BW) of 50.1 ± 2.2 kg were randomly assigned to three treatment groups on the basis of BW. Each treatment had 60 pigs arranged in 12 replicates of 5 pigs for a 10-week trial. The dietary treatments consisted of a corn - soybean meal basal diet (CON); and a basal diet supplemented with NTS at 2 g/kg (NTS2) or 4 g/kg feed (NTS4). An increase (linear effect, P < 0.05) in BW during days 35 and 70 and an increase in average daily gain (ADG) (linear effect, P < 0.05) were observed in pigs fed increasing level of NTS during days 1–35 and 36–70 as well as during the overall experiment period (day 1–70). The inclusion of increasing level of NTS reduced serum low-density lipoprotein (LDL) cholesterol (linear effect, P < 0.05) and increased (linear effect, P < 0.05) serum high-density lipoprotein (HDL) cholesterol concentrations at days 35 and 70, respectively. At day 70, the backfat and lean percentage were increased (linear effect, P < 0.05) as the level of NTS increased in the diet. A linear reduction (P < 0.05) in cooking loss and drip loss at day 7 of meat sample storage was elicited by increasing dietary NTS levels. A linear increase (P < 0.05) in eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA) and polyunsaturated fatty acid (PUFA) in the loin muscle and a linear increase (P < 0.05) in oleic acid, linoleic acid, DHA, and PUFA concentrations were observed in the meat sample of belly fat obtained from pigs receiving an increasing NTS level. In conclusion, positive effects of NTS were observed in body weight, daily gain, lipid profile and meat quality, suggesting that 4 g/kg non-toxic sulfur is beneficial for pigs.

Supplementation with galacto-oligosaccharides in early life persistently facilitates the microbial colonization of the rumen and promotes growth of preweaning Holstein dairy calves.

We aimed to determine the effects of dietary supplementation with galacto-oligosaccharides (GOS) on the growth performance, serum parameters, and the rumen microbial colonization and fermentation of pre-weaning dairy calves. The study comprised 2 phases of 28 and 42 d, respectively. During phase 1, 24 newborn female Holstein dairy calves were randomly allocated to consume a diet supplemented with 10 g/d GOS (GOS, n = 12) or not (CON, n = 12). Thereafter, during phase 2, the GOS group was further divided into 2 groups: one that continued to consume GOS (GOSC, n = 6) and one that no longer consumed GOS (GOSS, n = 6), alongside the CON group. Galacto-oligosaccharides increased the average daily gain (ADG), body weight, feed efficiency, and serum high-density lipoprotein-cholesterol concentration of dairy calves during phase 1 (P < 0.05). Supplementation with GOS for the entire study reduced the incidence of diarrhea and increased the serum total protein and Ca concentrations (P < 0.05) compared with the CON group. The effect of GOS supplementation persisted after it was stopped because the ADG and final body weight of the GOSS group were higher than those of the CON group (P < 0.05). Furthermore, the GOSS group showed a persistently lower incidence of diarrhea and greater colonization of the rumen with probiotics, at the expense of less beneficial bacteria, which would promote ruminal fermentation and microbial protein synthesis. These findings provide a theoretical basis for the rational application of prebiotics and have important practical implications for the design of early life dietary interventions in dairy calf rearing.

Lipid levels, apolipoproteins, and risk of incident atrial fibrillation in men: A report from the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD)

Apolipoproteins are associated with risk of coronary heart disease but the association with risk of incident atrial fibrillation (AF) has been inconsistent. This study investigated the association of apolipoproteins A-1 (apoA-1) and B (apoB), and lipid levels including triglyceride (TG), total cholesterol (TC), very low-density lipoprotein cholesterol (VLDL-C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), with the risk of new-onset AF. A total of 2533 men from the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42-60 years, were studied. Cox proportional hazards adjusted for potential confounders was used to estimate hazard ratio (HR) of incident events across serum lipid, lipoprotein, and apoA-1 and apoB concentrations. During the mean follow-up of 22.4 years, 594 AF cases occurred. Cox proportional hazards regression indicated that higher serum HDL-C and apoA-1 concentrations were associated with lower risk of AF [the extreme-quartile multivariable-adjusted HR 0.72 (95% CI 0.57-0.92, P=0.02) for HDL-C, and 0.72 (95% CI 0.52-1.00, P=0.05)] for apoA-1]. No significant associations were observed for apoB and other lipids (TC, VLDL-C, LDL-C, non-HDL-C, and TG) with risk of incident AF. Over the time of follow-up in this study lower new-onset incident AF was in association with higher HDL-C and apo-A1 levels. Future studies should investigate mechanisms underlying the association of low HDL-C and low apoA1 with higher risk of incident AF.

Common variant rs6564851 near the beta-carotene oxygenase 1 gene is associated with plasma triglycerides levels in middle-aged Mexican men adults

Dyslipidemias have been linked to an increased risk of adverse health outcomes, including cardiovascular disease, type 2 diabetes, and the metabolic syndrome. Recent reports have associated the beta-carotene oxygenase 1 (BCO1) gene with lipid metabolism, mainly reducing total cholesterol and increasing high-density lipoprotein-cholesterol (HDL-C) concentrations. The hypothesis of this study was that the variant rs6564851 near the BCO1 gene is associated positively with the lipid profile in middle-aged Mexican adults. This study included 1441 Mexicans older than 40 years of age from the Health Workers Cohort Study (HWCS). Genotyping was conducted using a predesigned TaqMan assay. Lipid profile was measured with standardized procedures. Our results showed that the men carrying at least 1 T allele had higher serum triglyceride concentrations than GG homozygous (GG: 146.5 mg/dL; GT: 175 mg/dL; and TT: 184 mg/dL; P = .008). The variant rs6564851 showed a risk associated with the serum triglyceride concentrations(odds ratio [OR], 2.77; P = .002) only in the male group. However, we did not observe significant differences in the serum total cholesterol, HDL-C, and low-density lipoprotein-cholesterol concentrations in both sexes. Our study provides evidence that the variant rs6564851 is negatively associated with the triglyceride concentrations in middle-aged Mexican male adults in the HWCS. This knowledge can be the basis for developing effective nutritional strategies according to sex and the genetic variants present in an individual. Further studies in independent populations are required to validate these findings and determine the mechanism of the association sex dependent.

Comparison of Various Lipid Levels in Patients with B-Thalassemia Major with that of Normal Individuals

Background: Thalassemia is the most common heterogeneous group of genetic disorders in which the production of normal hemoglobin (Hb) is partly or completely suppressed because of defective synthesis of one or more globin chains that vary widely in severity from asymptomatic forms to severe or even fatal entities. Aim of this study is to compare of various lipid levels in patients with b-thalassemia major with that of normal individuals. Methods: In this cross sectional study, 30 children (case) previously diagnosed as beta thalassemia major were evaluated for serum lipid levels who were admitted at the Department of Pediatrics in DMCH &amp; Thalassemia center of Dhaka Shishu Hospital from January 2012 to December 2012. The control group included 30 ages &amp; sex matched healthy participants. Serum lipids profiles (total cholesterol, triglycerides, LDL­ cholesterol, and HDL cholesterol) as well as hemoglobin, MCV, MCH &amp; MCHC were compared between the two groups. P value &lt; 0.05 was considered statistically significant. Serum total cholesterol (TC), Triglycerides (TG) and HDL cholesterol concentrations were measured by using Photoelectric Colorimeter (ERMA INC, model no AE-30F, made in Japan) in clinical biochemistry department of Dhaka Medical College. Results: Hematological tests showed the mean haemoglobin level in thalassemia group was 7.23 gm/dl with standard deviation of 1.23 whereas in control group the mean haemoglobin level was 10.37 gm/dl with standard deviation of 1.22. There was significant differences between two groups (p=.001). Mean MCV, MCH and MCHC in thaiassemic group were significantly lower [69.83 fl (SD 8.34), 23.10 pgm (SD 3.57) and 28.03% (SD-2.58)] than those in their control counterpart [8323 fl (SD 4.97), 29.23 pgm (SD 2.43) and 31.20% (SD-1.83)] respectively (p = 0.001 in all parameters). Beta thalassemia major patients had significantly lower high-density lipoprotein (HDL) and low-density lipoprotein (LDL) compare with controls (p&lt;0.001). ......

Loss-of-function mutation in Pcsk1 increases serum APOA1 level and LCAT activity in mice

BackgroundThe convertase subtilisin/kexin family 1 gene (PCSK1) has been associated in various human genetics studies with a wide spectrum of metabolic phenotypes, including early-onset obesity, hyperphagia, diabetes insipidus, and others. Despite the evident influence of PCSK1 on obesity and the known functions of other PCSKs in lipid metabolism, the role of PCSK1 specifically in lipid and cholesterol metabolism remains unclear. This study evaluated the effect of loss of PCSK1 function on high-density lipoprotein (HDL) metabolism in mice.ResultsHDL cholesterol, apolipoprotein A1 (APOA1) levels in serum and liver, and the activities of two enzymes (lecithin-cholesterol acyltransferase, LCAT and phospholipid transfer protein, PLTP) were evaluated in 8-week-old mice with a non-synonymous single nucleotide mutation leading to an amino acid substitution in PCSK1, which results in a loss of protein’s function. Mutant mice had similar serum HDL cholesterol concentration but increased levels of serum total and mature APOA1, and LCAT activity in comparison to controls.ConclusionsThis study presents the first evaluation of the role of PCSK1 in HDL metabolism using a loss-of-function mutant mouse model. Further investigations will be needed to determine the underlying molecular mechanism.

Effects of Dietary Pork Fat Cooked Using Different Methods on Glucose and Lipid Metabolism, Liver Inflammation and Gut Microbiota in Rats.

Cooking may affect the nutritional value of pork fat, and, nowadays, people have been paying an increasing amount of attention to the method of cooking. In this study, the effects of dietary pork fat cooked using different methods on body metabolism and intestinal microbes were studied in rats. Fat was extracted from pork belly meat cooked using three methods: braising (braising cooking method, BCM), stewing (SCM) and deep fat frying (DCM). The three types of pork fat were added to animal feed, and the effects of each on body weight, glucose and lipid metabolism, liver inflammation and intestinal microbes in rats were compared with the effects of soybean oil-treated feed (SO) and a blank control (BC). Rats in all three groups fed with cooked pork fat exhibited significant increases in body weight compared with the controls across the experimental feeding period. Furthermore, all three types of pork fat led to significant changes in the serum concentrations of triglycerides (TG) and total cholesterol (TC) relative to the controls, with the greatest increases in TG and TC in the BCM and DCM groups, respectively. All three types of pork fat led to significant decreases in serum high-density lipoprotein cholesterol concentrations relative to the controls, with the lowest concentration in the SCM group. All three types of pork fat also led to significant increases in low-density lipoprotein cholesterol concentrations relative to the controls, with the smallest increase in the DCM group. Rats in the SCM group had the highest level of liver fat deposition, followed by those in the BCM, DCM, SO and BC groups. Compared with the controls, the three groups fed with different types of cooked pork fat had significantly lower hepatic expression of nuclear transcription factor kappa B (NF-κB). The expression levels of NF-κB in the DCM and SO groups were significantly lower than those in the other groups. The abundance of Proteobacteria species in the intestines of rats was significantly lower in the BC group than in the other groups fed with cooked pork fat, and the abundance of Bacteroidetes species was significantly lower in the BCM, SCM and DCM groups than in the BC and SO groups. From the changes in the abundance of Firmicutes and Bacteroides, pork fat in the three cooking methods has a certain potential to promote the production of body obesity.