Blood Lipid Concentrations Research Articles

Dysregulation of the Lysophosphatidylcholine/Autotaxin/Lysophosphatidic Acid Axis in Acute-on-Chronic Liver Failure Is Associated With Mortality and Systemic Inflammation by Lysophosphatidic Acid-Dependent Monocyte Activation.

Acute-on-chronic liver failure (ACLF) is characterized by systemic inflammation, monocyte dysfunction, and susceptibility to infection. Lysophosphatidylcholines (LPCs) are immune-active lipids whose metabolic regulation and effect on monocyte function in ACLF is open for study. Three hundred forty-two subjects were recruited and characterized for blood lipid, cytokines, phospholipase (PLA), and autotaxin (ATX) concentration. Peripheral blood mononuclear cells and CD14+ monocytes were cultured with LPC, or its autotaxin (ATX)-derived product, lysophosphatidic acid (LPA), with or without lipopolysaccharide stimulation and assessed for surface marker phenotype, cytokines production, ATX and LPA-receptor expression, and phagocytosis. Hepatic ATX expression was determined by immunohistochemistry. Healthy volunteers and patients with sepsis or acute liver failure served as controls. ACLF serum was depleted in LPCs with up-regulated LPA levels. Patients who died had lower LPC levels than survivors (area under the receiver operating characteristic curve, 0.94; P<0.001). Patients with high-grade ACLF had the lowest LPC concentrations and these rose over the first 3days of admission. ATX concentrations were higher in patients with AD and ACLF and correlated with Model for End-Stage Liver Disease, Consortium on Chronic Liver Failure-Sequential Organ Failure Assessment, and LPC/LPA concentrations. Reduction in LPC correlated with higher monocyte Mer-tyrosine-kinase (MerTK) and CD163 expression. Plasma ATX concentrations rose dynamically during ACLF evolution, correlating with IL-6 and TNF-α, and were associated with increased hepatocyte ATX expression. ACLF patients had lower human leukocyte antigen-DR isotype and higher CD163/MerTK monocyte expression than controls; both CD163/MerTK expression levels were reduced in ACLF ex vivo following LPA, but not LPC, treatment. LPA induced up-regulation of proinflammatory cytokines by CD14+ cells without increasing phagocytic capacity. ATX up-regulation in ACLF promotes LPA production from LPC. LPA suppresses MerTK/CD163 expression and increases monocyte proinflammatory cytokine production. This metabolic pathway could be investigated to therapeutically reprogram monocytes in ACLF.

Associations of Changes in Blood Lipid Concentrations with Changes in Dietary Cholesterol Intake in the Context of a Healthy Low-Carbohydrate Weight Loss Diet: A Secondary Analysis of the DIETFITS Trial.

In 2015, the Dietary Guidelines for Americans (DGA) eliminated the historical upper limit of 300 mg of dietary cholesterol/day and shifted to a more general recommendation that cholesterol intake should be limited. The primary aim of this secondary analysis of the Diet Intervention Examining the Factors Interacting With Treatment Success (DIETFITS) weight loss diet trial was to evaluate the associations between 12-month changes in dietary cholesterol intake (mg/day) and changes in plasma lipids, particularly low-density lipoprotein (LDL) cholesterol for those following a healthy low-carbohydrate (HLC) diet. Secondary aims included examining high-density lipoprotein (HDL) cholesterol and triglycerides and changes in refined grains and added sugars. The DIETFITS trial randomized 609 healthy adults aged 18–50 years with body mass indices of 28–40 kg/m2 to an HLC or healthy low-fat (HLF) diet for 12 months. Linear regressions examined the association between 12-month change in dietary cholesterol intake and plasma lipids in 208 HLC participants with complete diet and lipid data, adjusting for potential confounding variables. Baseline dietary cholesterol intake was 322 ± 173 (mean ± SD). At 12 months, participants consumed an average of 460 ± 227 mg/day of dietary cholesterol; 76% consumed over the previously recommended limit of 300 mg/day. Twelve-month changes in cholesterol intake were not significantly associated with 12-month changes in LDL-C, HDL-C, or triglycerides. Diet recall data suggested participants’ increase in dietary cholesterol was partly due to replacing refined grains and sugars with eggs. An increase in daily dietary cholesterol intake to levels substantially above the previous 300 mg upper limit was not associated with a negative impact on lipid profiles in the setting of a healthy, low-carbohydrate weight loss diet.

Significant effects of Ganoderma lucidum polysaccharide on lipid metabolism in diabetes may be associated with the activation of the FAM3C-HSF1-CAM signaling pathway.

Diabetes is a threat to patient health worldwide. Type 2 diabetes (T2DM), one of the two main types of diabetes, is a long-term metabolic disease caused by heredity and environmental factors. It has been reported that Ganoderma lucidum polysaccharide (GLP) significantly decreased the concentration of blood glucose, promoted insulin secretion, improved glucose tolerance and regulated the concentration of blood lipids. In the present study, a T2DM model was established in db/db mice, following which T2DM mice were treated with GLP (100 and 400 mg/kg) for 8 weeks, with MET used as the positive control. The glycosylated hemoglobin (HbAlc) and fasting blood glucose (FBG) levels, and diabetes-associated clinical chemistry indexes were detected in the blood and serum of each mouse. Hematoxylin and eosin, and oil red O staining were performed on the livers of each mouse to evaluate the level of liver fat. The expression levels of family with sequence similarity 3 (FAM3C), heat shock factor 1 (HSF1), calmodulin (CaM), AKT and phosphorylated (p)-AKT were detected in the hepatocytes of T2DM mice using reverse transcription-quantitative PCR and western blotting. The results demonstrated that the unbalanced levels of HbAlc, FBG and diabetes-related index in T2DM mice were significantly improved by treatment with GLP. Lipid droplets in the hepatocytes of mice shrank in the GLP groups compared with the model control group. The expression levels of FAM3C, HSF1, CaM and p-AKT/AKT in the hepatocytes of T2DM mice were significantly increased following treatment with GLP. In conclusion, GLP exerted significant effects on lipid metabolism in diabetes, which may be associated with the activation of the FAM3C-HSF1-CaM signaling pathway.

Intake of a Mediterranean Diet Reduces Atherogenic Lipid Profiles but the Effect Is Diminished by Daily Egg Intake

Abstract Objectives A Mediterranean diet (Med Diet) decreases atherogenic lipoproteins and cardiovascular disease (CVD) risk. It is unknown how high cholesterol intake within a Med Diet will affect these parameters. The objective of this project was to evaluate the daily inclusion of whole eggs, a high cholesterol food, in the Med Diet on lipid and lipoprotein profiles. Methods Overweight to obese men (8) and women (25) were recruited into a randomized, cross-over designed, controlled feeding study evaluating three isocaloric test diets: a) Control –average American diet from What We Eat in America, b) Med Diet, and c) Med Diet plus whole, fresh eggs (1 whole egg/1000 kcal; Med Diet + Egg). The Control and Med Diet contained egg substitute. Participants were directed to consume only those foods provided during each 4-week diet treatment period. Each treatment period was separated by &amp;gt; 4-week washout period. Fasting blood was taken pre- and post-treatment for determination of lipid concentrations, lipoprotein particle size and number. Results Intake of the Control and Med Diet, but not the Med Diet + Egg, decreased (time effect, P &amp;lt; 0.05) total cholesterol and low density lipoprotein (LDL) concentrations, but an overall diet treatment effect did not occur. Med Diet, but not Control or Med Diet + Egg, reduced (time effect, P &amp;lt; 0.05) triglyceride concentrations, but an overall treatment effect did not occur. Particle numbers (P &amp;lt; 0.05) were reduced (P &amp;lt; 0.05) for intermediate density lipoprotein (26%) and total LDL (8%) by Med Diet intake but not by the other diets, and an overall treatment effect was not observed. Very low density lipoprotein size was reduced (P &amp;lt; 0.05) by Med Diet intake and an overall treatment effect occurred (P = 0.04). Variability in responses was assessed by hierarchical clustering heatmap analysis of blood lipid responses. Three main categories of responses types were present but not defined by dietary treatment. Conclusions Daily intake of a Mediterranean diet meal pattern or an average American diet without whole eggs reduced blood lipid and/or lipoprotein concentrations associated with CVD risk; addition of daily egg intake blunted these reductions. However, the variability in the study population responses warrants further nutrigenomic exploration. Funding Sources USDA-ARS 3062-53000-001-00D and the American Egg Board.

A correlation study of the relationships between nonalcoholic fatty liver disease and serum triglyceride concentration after an oral fat tolerance test

BackgroundNonalcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases worldwide. Triglyceride (TG) accumulation is central to NAFLD development. People now spend most of their day in the postprandial state, and the measurement of postprandial blood lipid concentration can make up for the lack of simple detection of fasting blood lipids. Postprandial triglyceride (PTG) is commonly used as a surrogate for postprandial blood lipid concentrations, and many studies have shown that PTG is a risk factor for NAFLD. The aim of the present study was to investigate the relationship between PTG concentration during oral fat tolerance testing (OFTT) and NAFLD.MethodsA total of 472 Chinese adults, aged 25 to 65 years, were enrolled in the study. All the participants underwent OFTT. The serum concentrations of TG and other lipids were measured, and their relationships with NAFLD were analyzed.ResultsOf the 472 participants, 155 were diagnosed with NAFLD. The fasting and postprandial TG concentrations of the participants with NAFLD were higher than those of healthy participants (P < 0.05). The TG concentrations of the healthy participants peaked 4 h postprandially, whereas those of the participants with NAFLD peaked 6 h postprandially and reached higher peak values. Postprandial TG concentration was significantly associated with a higher risk of NAFLD.ConclusionsHigh PTG is positively related to a higher risk of NAFLD, and the PTG concentrations of patients with NAFLD are higher than in healthy individuals, with a delayed peak. Therefore, 4-h PTG may represent a potential marker of NAFLD.Trial registrationChiCTR1800019514.

Nutrient Intake and Status of German Children and Adolescents Consuming Vegetarian, Vegan or Omnivore Diets: Results of the VeChi Youth Study.

There is a lack of data on associations between modern vegetarian and vegan diets and health among children and adolescents. The aim of the Vechi Youth Study was to cross-sectionally examine anthropometry, dietary intakes and nutritional status in a sample of 149 vegetarian, 115 vegan and 137 omnivore children and adolescents (6–18 years old, mean age: 12.7 ± 3.9 years). Group differences of dietary intake (calculated from three-day dietary records), nutrient biomarker and blood lipid concentrations were assessed using an analysis of covariance, adjusted for sex, age and other covariates. The total energy intake did not differ significantly between groups, but intake of carbohydrates was higher among vegetarians and vegans than among omnivores (p = 0.0002, respectively). The median protein intake exceeded 0.9 g/kg body weight/day in all diet groups and was lowest among vegetarians (p < 0.02). There was no significant difference of haemoglobin, vitamin B2, 25-OH vitamin D3, HDL-C and triglycerides blood concentrations between diet groups. Vegan participants had higher folate concentrations than vegetarian participants (p = 0.0053). Ferritin concentration was significantly higher in omnivores than in vegetarians (p = 0.0134) and vegans (p = 0.0404). Vegetarians had lower concentrations of holotranscobalamin (p = 0.0042) and higher concentrations of methylmalonic acid (p = 0.0253) than omnivores. Vegans had the lowest non-HDL-C and LDL-C concentrations in comparison to vegetarians (p = 0.0053 and p = 0.0041) and omnivores (p = 0.0010 and p = 0.0010). A high prevalence (>30%) of 25-OH vitamin D3 and vitamin B2 concentrations below reference values were found irrespective of the diet group. In conclusion, the Vechi Youth Study did not indicate specific nutritional risks among vegetarian and vegan children and adolescents compared to omnivores.

Associations between Inhaled Corticosteroid Use in the First 6 Years of Life and Obesity-related Traits.

Rationale: Infants and young children might be particularly likely to experience the potential clinical side effects of inhaled corticosteroids (ICSs) on body mass index (BMI), adiposity rebound (AR), and body composition, but this has rarely been studied in long-term studies in this age group. Objectives: To determine the association between ICS exposure in the first 6 years of life and the BMI, AR, body composition, and blood lipid concentrations. Methods: Children from the two mother-child cohorts of the COPSAC (Copenhagen Prospective Studies on Asthma in Childhood) were included. ICS use was registered prospectively to age 6 years, and the cumulative dose was calculated. Multiple linear regression models were used for analysis. Measurements and Main Results: A total of 932 (84%) of the 1,111 children from the COPSAC cohorts had BMI data, 786 (71%) had dual-energy X-ray absorptiometry scan data at the age of 6 years, and 815 (73%) had an AR age calculated. Two hundred ninety-one children (31%) received a cumulative ICS dose higher than that from 10 weeks of standard treatment before the age of 6. ICS treatment during 0-6 years of age was associated with an increased BMI z-score (0.05 [95% confidence interval, 0.005 to 0.09] SDs per each year of standard treatment; P = 0.03) an earlier age at AR (-0.18 [95% confidence interval, -0.28 to -0.08] yr; P = 0.0006), and a 2% increased geometric mean android fat percentage (P = 0.05). ICS exposure and dual-energy X-ray absorptiometry scan data were not associated. Conclusions: ICS use in early childhood was associated with an increased BMI z-score at age 6, an earlier AR, and a trend of association with an increased android body fat percentage.

Improvements in Physical Fitness are Associated with Favorable Changes in Blood Lipid Concentrations in Children.

Although accumulating evidence suggests the benefits of cardiorespiratory fitness and muscular fitness, little knowledge exists on how other physical fitness (PF) components are associated with cardiovascular disease (CVD) risk markers in children. Additionally, much of the relevant evidence is from longitudinal studies with CVD risk markers at a single time point (i.e., baseline) rather than changes in PF. The purpose of the present study was to examine whether initial 1-year changes in different performance measures of PF (i.e., endurance performance, muscular strength/endurance, flexibility, agility, and speed) can predict the subsequent changes (2-year change) in blood lipid concentrations in children. This 2-year longitudinal study included a total of 251 Japanese children (mean age 9.2 ± 0.4). PF tests were performed to comprehensively evaluate the participant's fitness levels (handgrip strength [upper body muscular strength], bent-leg sit-ups [muscular endurance], sit-and-reach [flexibility], side-step [agility], 20-meter shuttle run [endurance performance], 50-meter sprint [speed], standing long jump [lower body muscular strength], and softball throw [explosive arm strength and throwing ability]). Fasting lipid profile was assayed for triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and non-HDL-C concentration. Multilevel linear regressions were used to examine the associations between the preceding changes (over 1-year) in PF and subsequent changes (over 2-years) in blood lipid concentrations. We also examined the simultaneous associations between 2-year changes in PF and 2-year changes in blood lipid concentrations. For boys, preceding improvement in handgrip strength was negatively associated with TG concentration (β = -0.260, p = 0.030); improvements in bent-leg sit-ups were negatively associated with clustered lipid scores (β = -0.301, p = 0.038) and non-HDL-C (β = -0.310, p = 0.044); and improvements in 50m sprinting were associated with subsequent changes in non-HDL-C (β = 0.348, p = 0.006) and LDL-C (β = 0.408, p = 0.001). For girls, improvements in handgrip strength was negatively associated with TG concentration (β = -0.306, p = 0.017); and improvements in standing long jump were negatively associated with non-HDL-C (β = -0.269, p = 0.021) and LDL-C (β = -0.275, p = 0.019). For boys and girls, there were no significant simultaneous associations between 2-year changes in PF and 2-year changes in blood lipid concentrations. In conclusion, preceding change in physical fitness in relation to change in blood lipid concentration likely reflect a physiological adaptation to growth and maturation since these associations diminished in the subsequent year.

Management of Hyperlipidaemia through Ayurvedic Intervention

The potential of hyperlipidemia to engage in the pathology of atherosclerotic diseases such as coronary heart disease, which dominates the scenario of diseases causing morbidity and mortality in the world. Hyperlipidemia is defined as elevated serum levels of cholesterol, triglycerides, or both. It is characterized by abnormally elevated lipid concentrations in blood caused by impaired lipid and lipoprotein metabolism and has the potential to cause a variety of complications such as cardiovascular disease, diabetes, obesity, hypertension, atherosclerosis, and so on. Hyperlipidemia is classified as Medoroga in Ayurveda. The results obtained for the lipid profile parameter demonstrated a significant change. The difference in total serum cholesterol is 36 mg/dl, serum triglycerides is 32 mg/dl, serum LDL is 40 mg/dl, serum VLDL is 15 mg/dl and serum HDL is -3 mg/dl.

Lactobacillus paracasei DTA81, a cholesterol-lowering strain having immunomodulatory activity, reveals gut microbiota regulation capability in BALB/c mice receiving high-fat diet.

Aims In‐vitro/In‐vivo evaluation of cholesterol‐lowering probiotic strain Lactobacillus paracasei DTA81 and the possible connection with the gut microbiota modulation.Methods and ResultsIn the present study, strain DTA81 has been evaluated for the possible influence on blood lipid and glucose concentrations, modulation of the immune system, gastrointestinal survivability and modulation of gut microbiota in BALB/c mice receiving a high‐fat diet. After 6 weeks of treatment, a significant reduction of total cholesterol and fasting blood sugar (FBS) among animals treated with L. paracasei DTA81 has been recorded. Comparison of colon tissue levels of different cytokines revealed a significant reduction of the inflammatory cytokine interleukin‐6. The comparison of gut microbiota using the 16S rRNA approach indicated that the treatment with L. paracasei DTA81 significantly increased the taxa Bacteroidetes and Coprococcus. Moreover, the genome of DTA81 was sequenced for the in‐silico assessment, and the analysis indicated the presence of cholesterol assimilation‐related genes as well as the absence of negative traits such as transmissible antibiotic resistance genes, plasmids and prophage regions.ConclusionThe outcome of this study revealed the in‐vitro and in‐vivo properties of L. paracasei DTA81 and the possible mechanism between consumption of this strain, the abundance of Bacteriodetes/Coprococcus taxa, immunomodulatory activity and the subsequent reduction of cholesterol/FBS in BALB/c mice.Significance and Impact of the Study Lactobacillus paracasei DTA81 as a non‐pharmacological potential probiotic supplement can influence metabolic homeostasis in individuals, particularly those adopting high‐fat diets, and it can contribute to reduce coronary heart disease.

Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices

Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10−72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10−4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10−5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids.

Relationships between Maternal Dietary Patterns and Blood Lipid Levels during Pregnancy: A Prospective Cohort Study in Shanghai, China.

The relationships between maternal dietary patterns and blood lipid profile during pregnancy have not been well understood. We aimed to analyze the dietary patterns of pregnant women and their associations with blood lipid concentrations during pregnancy. A cohort of 1008 Chinese pregnant women were followed from 10–15 weeks of gestation to delivery. Their dietary patterns were identified using a principal component analysis. The relationships between dietary pattern score and maternal blood lipid concentrations were assessed using both multivariate linear regression models and generalized estimating equation (GEE) models. Five different dietary patterns were identified. GEE showed that a high score for the fish-shrimps pattern was associated with higher concentrations of total cholesterol (TC) (β = 0.11), low-density lipoprotein cholesterol (LDL-C) (β = 0.07), and high-density lipoprotein cholesterol (HDL-C) (β = 0.03), with all p values < 0.001. In contrast, a high tubers-fruit-vegetables pattern score was associated with lower concentrations of TC (β = −0.12), LDL-C (β = −0.07), and HDL-C (β = −0.03), with all p values < 0.001. In addition, dietary protein, carbohydrate, and cholesterol intake significantly contributed to the associations between the fish-shrimps dietary pattern and blood lipid concentrations. Predominant seafood consumption is associated with higher cholesterol concentrations, whereas predominant tuber, fruit, and vegetable consumptions are associated with lower cholesterol concentrations during pregnancy.

New therapeutic agents marketed in 2020: Part 2

New therapeutic agents marketed in 2020: Part 2

A218 A CASE REPORT OF PSEUDOHYPONATREMIA IN CHOLESTATIC LIVER DISEASE

Abstract Background True hyponatremia in the setting of cholestatic liver disease may signify cirrhosis with fluid overload, and is therefore an ominous sign of deteriorating liver function. In pediatric liver transplant candidates, it is associated with increased waitlist mortality. Pseudohyponatremia however, is a falsely low measurement of plasma sodium when measured by indirect potentiometry. Pseudohyponatremia secondary to hypercholesterolemia is a phenomenon that occurs due to a reduced aqueous fraction of the plasma when levels of cholesterol or triglycerides are greatly elevated. Severe hypercholesterolemia due to Lipoprotein X accumulation may be the cause of pseudohyponatremia in biliary obstruction or cholestasis. Aims To describe a case of pseudohyponatremia secondary to hypercholesterolemia in an infant with Alagille syndrome (ALGS) and cholestatic liver disease. Methods This 7 month-old male with ALGS (confirmed JAGGED1 mutation) and severe cholestasis, failure to thrive, and pruritus, developed new-onset progressive hyponatremia as low as 121 mmol/L at an outside institution. He was therefore transferred to our center for liver transplant assessment due to concerns of progressive liver dysfunction and for management of the hyponatremia. Results Upon admission, the patient was jaundiced but euvolemic, with no evidence of ascites or peripheral edema. Laboratory work drawn at our institution showed conjugated bilirubin of 180 mmol/L, ALT 300 U/L, AST 250 U/L, and GGT 1200 U/L. INR was 1.1 and albumin of 35 g/L. The cholesterol was elevated above 16.8 mmol/L, with high triglycerides 2.68 mmol/L, and the serum appeared visibly lipemic. The sodium level was 138 mmol/L as measured by direct potentiometry due to the visible lipemia. The osmolality of 288 mmol/kg was normal with a normal osmolar gap. Urine osmolality and sodium were also normal. He underwent routine evaluation and was listed for a liver transplant due to the profound cholestasis and growth failure. Conclusions Pseudohyponatremia is an important entity to recognize when caring for patients with cholestatic liver disease and hyponatremia. Both direct potentiometry and indirect potentiometry are currently used for sodium testing in blood in biochemistry laboratories. These measurement techniques show good agreement as long as protein and lipid concentrations in blood are normal, however, hyperlipidemia is a well-recognized cause for error in sodium estimation. It is therefore imperative to evaluate apparent hyponatremia correctly, especially when the patient appears euvolemic clinically and by normal serum osmolality. In this clinical setting, pseudohyponatremia is the likely cause and a workup should be carried out to identify possible underlying etiologies, the most probable being hypercholesterolemia. Failure to recognize this phenomenon may lead to unnecessary and potentially harmful treatments and interventions. Funding Agencies None

Organophosphate Flame Retardants, Highly Fluorinated Chemicals, and Biomarkers of Placental Development and Disease During Mid-Gestation.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) and organophosphate flame retardants (OPFRs) are chemicals that may contribute to placenta-mediated complications and adverse maternal-fetal health risks. Few studies have investigated these chemicals in relation to biomarkers of effect during pregnancy. We measured 12 PFASs and four urinary OPFR metabolites in 132 healthy pregnant women during mid-gestation and examined a subset with biomarkers of placental development and disease (n = 62). Molecular biomarkers included integrin alpha-1 (ITGA1), vascular endothelial-cadherin (CDH5), and matrix metalloproteinase-1 (MMP1). Morphological endpoints included potential indicators of placental stress and the extent of cytotrophoblast (CTB)-mediated uterine artery remodeling. Serum PFASs and urinary OPFR metabolites were detected in ∼50%-100% of samples. The most prevalent PFASs were perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonic acid (PFOS), with geometric mean (GM) levels of ∼1.3-2.8 (95% confidence limits from 1.2-3.1) ng/ml compared to ≤0.5 ng/ml for other PFASs. Diphenyl phosphate (DPhP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) were the most prevalent OPFR metabolites, with GMs of 2.9 (95% CI: 2.5-3.4) and 3.6 (95% CI: 2.2-3.1) ng/ml, respectively, compared to <1 ng/ml for bis(2-chloroethyl) phosphate (BCEP) and bis(1-chloro-2-propyl) phosphate (BCIPP). We found inverse associations of PFASs or OPFRs with ITGA1 or CDH5 immunoreactivity and positive associations with indicators of placental stress in multiple basal plate regions, indicating these chemicals may contribute to abnormal placentation and future health risks. Associations with blood pressure and lipid concentrations warrant further examination. This is the first study of these chemicals with placental biomarkers measured directly in human tissues and suggests specific biomarkers are sensitive indicators of exposure during a vulnerable developmental period.

Transient Receptor Potential Melastatin 2 Enhances Vascular Reactivity During Development of Atherosclerosis in Mice.

To investigate the function of transient receptor potential melastatin 2 (TRPM2) in vascular reactivity induced by 5-hydroxytryptamine (5-HT) in the aorta during development of atherosclerosis in mice. Forty mice were randomly divided into 4 groups: C57BL/6J on normal diet (C57 + ND), C57BL/6J on high-fat diet (C57 + HFD), apolipoprotein E gene knockout mice (ApoE-/-) on ND (ApoE-/- + ND), and ApoE-/- on HFD (ApoE-/- + HFD). They were fed with a ND or HFD for 16 weeks. Aortic TRPM2 expression and isometric contractions were analyzed. In the ApoE-/- + HFD group, body weight, blood glucose, and blood lipid concentrations were increased, and aortic plaques were developed. Compared with the other 3 groups, aortic TRPM2 mRNA and protein levels were significantly increased in the ApoE-/- + HFD group (P < 0.01). Aortic reactivity to 5-HT was enhanced in ApoE-/- + HFD mice with lower EC50 values. The enhanced reactivity to 5-HT was significantly inhibited by TRPM2 inhibitors, N-p-amylcinnamoyl anthranilic acid (1 µmol/l) and 2-aminoethyl diphenylborinate (10 µmol/l). Aortic TRPM2 expression is upregulated in ApoE knockout mice fed with a HFD. Upregulation of TRPM2 enhances 5-HT vascular reactivity during development of atherosclerosis.

Sex May Modulate the Effects of Combined Polyphenol Extract and L-citrulline Supplementation on Ambulatory Blood Pressure in Adults with Prehypertension: A Randomized Controlled Trial.

Increased blood pressure (BP), vascular dysfunction and inflammation are involved in the etiology of cardiovascular disease (CVD). Although several dietary components such as polyphenols and L-citrulline may help to control BP, their combined impact on ambulatory BP in individuals at risk of CVD remains unknown. The objective of this research was to investigate the short-term impact of supplementation with a combination of polyphenol extract and L-citrulline on ambulatory BP, endothelial function and inflammation. In a randomized double-blind parallel trial, 73 men and women with prehypertension were supplemented with a placebo (cellulose, n = 34, Plac) or 548 mg/day of polyphenols and 2 g/day of L-citrulline (n = 35, Suppl) for 6 weeks. The primary outcome of this study was the difference between groups in 24-h ambulatory diastolic BP (DBP) at week six. Secondary outcomes were a difference between groups at week six in ambulatory systolic BP (SBP), casual BP, serum lipids and high-sensitivity C-reactive protein (hs-CRP) concentrations and skin advanced glycation end products (AGEs). Potential interaction of treatment with sex was examined. Suppl had no impact on mean ambulatory SBP and DBP (p > 0.10 vs. placebo). Daytime and 24-h SBP were reduced with Suppl in women (p ≤ 0.01), but not in men (p ≥ 0.27). A non-significant reduction in AGEs was observed after Suppl compared to Plac among all participants (p = 0.07) and there was no difference in the concentrations of blood lipids (p > 0.20) or CRP (p = 0.36) between treatments at week six. Therefore, supplementation with polyphenol extract and L-citrulline for 6 weeks has no impact on ambulatory BP, blood lipids and CRP in adults with prehypertension. However, the polyphenol extract/L-citrulline supplement may reduce ambulatory SBP in women, but not in men. These preliminary results need further research efforts towards further documenting this sex-dependent BP response to supplementation with polyphenols and L-citrulline.

Prescribed exercise to Reduce Recidivism After Weight Loss-Pilot (PREVAIL-P): Design, methods and rationale

Clinically significant weight loss is associated with health benefits for overweight and obese adults. Participation in adequate amounts of physical activity is critical for weight maintenance. However, the recommended amount of physical activity needed to promote weight maintenance is based primarily on retrospective studies that quantified physical activity levels through questionnaires which tend to overestimate physical activity levels. In addition, the present literature has provided little data on the impact of these physical activity levels on cardiovascular and diabetes risk factors, which may have equal or more clinical importance than weight changes. The Prescribed Exercise to Reduce Recidivism After Weight Loss-Pilot (PREVAIL-P) study will evaluate the effect of aerobic exercise training amount on weight maintenance following clinically significant weight loss in overweight and obese adults (BMI 25–40 kg/m2) age 30–65 years. Participants (N = 39) will complete a 10-week OPTIFAST® weight loss program with supervised aerobic exercise training. Individuals who achieve ≥7% weight loss from baseline will be subsequently randomized to levels of aerobic training consistent with physical activity recommendations (PA-REC) or weight maintenance recommendations (WM-REC) for 18 additional weeks. The primary outcome of the PREVAIL-P study will be change in weight from the completion of OPTIFAST® program to the end of the study. Notable secondary measures include changes in clinically relevant cardiometabolic risk factors between study groups (e.g. blood lipids concentrations, oral glucose tolerance, arterial stiffness). This pilot study will be used to estimate the effect sizes needed for a randomized controlled trial on this topic.

Effect of PCSK9 inhibitor on lipoprotein particles in patients with acute coronary syndromes

BackgroundTo assess the effects of proprotein convertase subtilisin/kexin type 9 inhibitor (evolocumab) on lipoprotein particles subfractions with Nuclear Magnetic Resonance spectroscopy in patients with acute coronary syndromes.MethodsA total of 99 consecutive patients with ACS were enrolled and assigned to either the experimental group (n = 54) or the control group (n = 45). The combination therapy of PCSK9 inhibitor (Repatha®, 140 mg, q2w) and moderate statin (Rosuvastatin, 10 mg, qn) was administered in the experimental group, with statin monotherapy (Rosuvastatin, 10 mg, qn) in the control group. The therapeutic effects on lipoprotein particle subfractions were assessed with NMR spectroscopy after 8 weeks treatment, and the achievement of LDL-C therapeutic target in both groups were analyzed.ResultsIn the experimental group, after 8 weeks of evolocumab combination treatment, the concentrations of blood lipids (TC, LDL-C and its subfractions [LDL-1 to 6], VLDL-C and its subfractions [VLDL-1 to 5], IDL-C, and HDL-C), lipoprotein particles, and their subfractions [VLDL-P, IDL-P, LDL-P, and its subfractions [LDL-P1 to 6], apoB, and LP(a)] demonstrated therapeutic benefits with statistical significance (P < 0.05). The decrease in total LDL-P concentrations was mainly due to a decreased concentration of small-sized LDL particles (LDL-P 5 + 6), which was significantly more prominent than the decrease in medium-sized LDL-P (LDL-P3 + 4) and large-sized LDL-P (LDL-P1 + 2) (P < 0.001). According to lipid control target recommended by the latest China Cholesterol Education Program Expert Consensus in 2019, after 8 weeks treatment, 96.3% patients in the experimental group and 13.3% in the control group had achieved the LDL-C therapeutic target (P < 0.01).ConclusionsEvolocumab combination treatment for 8 weeks significantly improves the plasma lipid profiles in ACS patients, and significantly decrease the concentration of lipoprotein particles which might contribute to the pathonesis of atherosclerosis.

Feeding fermented palm kernel cake with higher levels of dietary fat improved gut bacterial population and blood lipid concentration but not the growth performance in broiler chickens

The study aimed to determine the effects of Weisella confusa SR-17b fermented PKC (LPKC) and different levels of dietary fats on the growth performance, caecal microbial population, and blood lipid profile concentration in broiler chickens raised in the tropical environment. During the starter period, all birds received the same basal diet. From d 22 to 35, broiler chickens were randomly fed with either (1) 20% LPKC based diet with 5% palm oil, (2) 20% LPKC-based diet with 9.5% palm oil, (3) 20% PKC-based diet with 5% palm oil or (4) 20% PKC-based diet with 9.5% palm oil.No significant difference was observed between LPKC and PKC diets on broilers' growth performance. LPKC-based diet reduced the caecal population of E. coli and serum triglyceride concentration. In terms of oil supplementation, both PKC- and LPKC-based diets required higher levels of dietary fat to maintain optimum growth performance. A higher level of dietary fat in the LPKC-/PKC-based diet reduced serum levels of triglycerides and lower-density lipoprotein cholesterol and lowered the caecal E. coli population. Highlights Feeding finisher diet based on fermented palm kernel cake has no effect on the overall growth performance but reduces gut E. coli population, and serum triglycerides levels. Incorporating 9.5% palm oil in the finisher diet is beneficial in improving final body weight and feed efficiency, reducing gut E. coli population, and modifying serum lipid profile. Diet with fermented palm kernel cake and 9.5% palm oil shows the best feed cost/kg of chicken produced.