Sphingolipid and Trimethylamine-N-Oxide (TMAO) Levels in Women with Obesity after Combined Physical Training.

Obesity causes metabolic changes, such as the development of cardiovascular diseases. Moreover, physical exercise promotes protection against these diseases. Thus, the objective of the present study was to evaluate whether combined physical training can improve the metabolic system of women with obesity, reducing plasma concentrations of trimethylamine N-oxide (TMAO) and sphingolipids, regardless of weight loss.

Integrated omics approach for the identification of HDL structure-function relationships in PCSK9-related familial hypercholesterolemia.

Background: The role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in dyslipidemia may go beyond its immediate effects on low-density lipoprotein receptor (LDL-R) activity.

Objective: This study aimed to assess PCSK9-derived alterations of high-density lipoprotein (HDL) physiology, which bear a potential to contribute to cardiovascular risk profile.

Methods: HDL was isolated from 33 patients with familial autosomal dominant hypercholesterolemia (FH), including those carrying PCSK9 gain-of-function (GOF) genetic variants (FH-PCSK9, n = 11), together with two groups of dyslipidemic patients employed as controls and carrying genetic variants in the LDL-R not treated (ntFH-LDLR, n = 11) and treated (tFH-LDLR, n = 11) with statins, and 11 normolipidemic controls.

Hepatic deletion of serine palmitoyl transferase 2 impairs ceramide/sphingomyelin balance, bile acids homeostasis and leads to liver damage in mice.

Ceramides (Cer) have been shown as lipotoxic inducers, which disturb numerous cell-signaling pathways, leading to metabolic disorders such as type 2 diabetes. In this study, we aimed to determine the role of de novo hepatic ceramide synthesis in energy and liver homeostasis in mice. We generated mice lacking serine palmitoyltransferase 2 (Sptlc2), the rate limiting enzyme of ceramide de novo synthesis, in liver under albumin promoter.

Effect of omega-3 fatty acid ethyl esters on postprandial arterial elasticity in patients with familial hypercholesterolemia.

Background: Impaired arterial elasticity reflects increased risk of atherosclerotic cardiovascular disease in patients with familial hypercholesterolemia (FH). Treatment with omega-3 fatty acid ethyl esters (ω-3FAEEs) in FH patients has been shown to improve postprandial triglyceride-rich lipoprotein (TRL) metabolism, including TRL-apolipoprotein(a) [TRL-apo(a)]. Whether ω-3FAEE intervention also improves postprandial arterial elasticity in FH has not been demonstrated.

Evaluation of hypercholesterolemia management in at-risk patients by cardiologists in France: a case vignette-based study.

This online interactive survey investigated lipid-lowering approaches of French cardiologists in high- and very high-cardiovascular risk patients with hypercholesterolemia. Physicians assessed three hypothetical patients at three clinic visits, and selected the patients' cardiovascular risk category, target low-density lipoprotein cholesterol (LDL-C) and treatment. A total of 162 physicians completed 480 risk assessments; 58% of assessments correctly categorized the hypothetical patients.

Untargeted lipidomic analysis of plasma from obese women submitted to combined physical exercise.

This study aimed to determine the changes of lipidome in obese women undergoing combined physical exercise training. Fourteen adult women with obesity (mean BMI and age, 33 kg/m and 34 ± 5 years), were submitted to combined physical training (aerobic and strength exercises, alternately, 55 min at 75-90% of the maximum heart rate, 3 times a week) for 8 weeks. All participants were evaluated before and after the training intervention for lipidome, anthropometric measurements, muscle strength, and maximum oxygen consumption (VOmax).

Effect of Omega-3 Fatty Acid Supplementation on the Postprandial Metabolism of Apolipoprotein(a) in Familial Hypercholesterolemia.

Aim: Lipoprotein(a) (Lp(a)) is a low-density lipoprotein-like particle containing apolipoprotein(a) (apo(a)) that increases the risk of atherosclerotic cardiovascular disease (ASCVD) in familial hypercholesterolemia (FH). Postprandial redistribution of apo(a) protein from Lp(a) to triglyceride-rich lipoproteins (TRLs) may also increase the atherogenicity of TRL particles. Omega-3 fatty acid (ω3FA) supplementation improves postprandial TRL metabolism in FH subjects.

Bariatric Surgery Improves the Atherogenic Profile of Circulating Methylarginines in Obese Patients: Results from a Pilot Study.

Bariatric surgery improves obesity-related comorbidities. Methylarginines are biomarkers of cardiometabolic risk, liver steatosis, and insulin resistance. Here, we aimed to investigate methylarginines in obese patients undergoing bariatric surgery and compared them to age- and sex-matched healthy subjects.

Stable Isotope Abundance and Fractionation in Human Diseases.

The natural abundance of heavy stable isotopes (C, N, O, etc.) is now of considerable importance in many research fields, including human physiology. In fact, it varies between tissues and metabolites due to isotope effects in biological processes, that is, isotope discriminations between heavy and light isotopic forms during enzyme or transporter activity.

Carrot Supplementation Improves Blood Pressure and Reduces Aortic Root Lesions in an Atherosclerosis-Prone Genetic Mouse Model.

Epidemiological studies have shown that carrot consumption may be associated with a lower risk of developing several metabolic dysfunctions. Our group previously determined that the Bolero (Bo) carrot variety exhibited vascular and hepatic tropism using cellular models of cardiometabolic diseases. The present study evaluated the potential metabolic and cardiovascular protective effect of Bo, grown under two conditions (standard and biotic stress conditions (BoBS)), in apolipoprotein E-knockout (ApoE) mice fed with high fat diet (HFD).

Large-scale screening of lipase acid deficiency in at risk population.

Background: Lysosomal acid lipase deficiency (LALD, OMIM#278000) is a rare lysosomal disorder with an autosomal recessive inheritance. The main clinical manifestations are related to a progressive accumulation of cholesteryl esters, triglycerides or both within the lysosome in different organs such as the liver, spleen, and cardiovascular system. A wide range of clinical severity is associated with LALD including a severe very rare antenatal/neonatal/infantile phenotype named Wolman disease and a late-onset form named cholesteryl ester storage disease (CESD).

10-Year Comparative Follow-up of Familial versus Multifactorial Chylomicronemia Syndromes.

Context: The relative incidence of acute pancreatitis, ischemic cardiovascular disease, and diabetes in hyperchylomicronemic patients exhibiting familial chylomicronemia syndrome (FCS) or multifactorial chylomicronemia syndrome (MCS) is unknown.

Objective: The objective was to study the occurrence of these events in FCS and MCS patients compared with the general population.

Methods: Twenty-nine FCS and 124 MCS patients, with genetic diagnosis, in 4 lipid clinics were matched with 413 controls.

Apple Supplementation Improves Hemodynamic Parameter and Attenuates Atherosclerosis in High-Fat Diet-Fed Apolipoprotein E-Knockout Mice.

Epidemiological studies describe the association between apple consumption and improved cardiovascular and metabolic dysfunction. Our recent multiparametric screening on cellular model studies has shown that apples exhibit vascular tropism including Granny Smith (GS) variety independently of the storage condition. The present study aimed to evaluate the cardiovascular and metabolic protection of supplementation of GS variety after storage in classic cold (GSCC) and extreme ultra-low oxygen conditions (GSXO) in the apolipoprotein E-deficient 8-week-old mice fed with high fat diet for 14 weeks.

Effect of fasting and feeding on apolipoprotein A-I kinetics in preβ-HDL, α-HDL, and triglyceride-rich lipoproteins.

The aim of this study was to compare the kinetics of apolipoprotein (apo)A-I during fed and fasted states in humans, and to determine to what extent the intestine contributes to apoA-I production. A stable isotope study was conducted to determine the kinetics of apoA-I in preβ high-density lipoprotein (HDL) and α-HDL. Six healthy male subjects received a constant intravenous infusion of H-leucine for 14 h.

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

Context: 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.

Objectives: 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.

A high-throughput mass spectrometry-based assay for large-scale profiling of circulating human apolipoproteins.

Apolipoproteins govern lipoprotein metabolism and are promising biomarkers of metabolic and cardiovascular diseases. Unlike immunoassays, MS enables the quantification and phenotyping of multiple apolipoproteins. Hence, here, we aimed to develop a LC-MS/MS assay that can simultaneously quantitate 18 human apolipoproteins [A-I, A-II, A-IV, A-V, B48, B100, C-I, C-II, C-III, C-IV, D, E, F, H, J, L1, M, and (a)] and determined apoE, apoL1, and apo(a) phenotypes in human plasma and serum samples.

An innovative lipid-lowering approach to enhance attainment of low-density lipoprotein cholesterol goals.

Aims: To improve attainment of LDL-cholesterol (LDL-c) targets, an expert group proposed an algorithm for lipid-lowering therapy during hospitalization for acute coronary syndrome and during follow-up. We aimed to assess adherence to this algorithm, and evaluate its impact on LDL-c levels and on attainment of therapeutic LDL-c targets in a population of post-acute coronary syndrome patients.

Methods And Results: Prospective, observational study including patients admitted for acute coronary syndrome between February 2017 and September 2018.

Plasma Trimethylamine N-Oxide and Risk of Cardiovascular Events in Patients With Type 2 Diabetes.

Objective: Even though trimethylamine N-oxide (TMAO) has been demonstrated to interfere with atherosclerosis and diabetes pathophysiology, the association between TMAO and major adverse cardiovascular events (MACE) has not been specifically established in type 2 diabetes (T2D).

Research Design And Methods: We examined the association of plasma TMAO concentrations with MACE and all-cause mortality in a single-center prospective cohort of consecutively recruited patients with T2D.

Results: The study population consisted in 1463 SURDIENE participants (58% men), aged 65 ± 10 years.

VLDL (Very-Low-Density Lipoprotein)-Apo E (Apolipoprotein E) May Influence Lp(a) (Lipoprotein [a]) Synthesis or Assembly.

Objective: To clarify the association between PCSK9 (proprotein convertase subtilisin/kexin type 9) and Lp(a) (lipoprotein [a]), we studied Lp(a) kinetics in patients with loss-of-function and gain-of-function mutations and in patients in whom extended-release niacin reduced Lp(a) and PCSK9 concentrations. Approach and Results: Six healthy controls, 9 heterozygous patients with familial hypercholesterolemia (5 with low-density lipoprotein receptor [] mutations and 4 with gain-of-function mutations) and 3 patients with heterozygous dominant-negative loss-of-function mutations were included in the preliminary study. Eight patients were enrolled in a second study assessing the effects of 2 g/day extended-release niacin.

Roux-en-Y gastric bypass, but not sleeve gastrectomy, decreases plasma PCSK9 levels in morbidly obese patients.

Aim: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a master regulator of low-density lipoprotein cholesterol (LDL-C) metabolism, acting as an endogenous inhibitor of the LDL receptor. While it has been shown that bariatric surgery differentially affects plasma LDL-C levels, little is known of its effects on plasma PCSK9 concentrations. Therefore, the present study aimed to: (i) investigate the effect of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on plasma PCSK9 concentrations; and (ii) correlate baseline or postoperative plasma PCSK9 concentration variations with anthropometric and metabolic parameters.

Efficacy and Safety of Alirocumab in Patients With Autosomal Dominant Hypercholesterolemia Associated With Proprotein Convertase Subtilisin/Kexin Type 9 Gain-of-Function or Apolipoprotein B Loss-of-Function Mutations.

Autosomal dominant hypercholesterolemia results from mutations affecting the low-density lipoprotein receptor pathway, including proprotein convertase subtilisin/kexin type 9 (PCSK9) gain-of-function mutations (GoFm) and apolipoprotein B (APOB) loss-of-function mutations (LoFm). This study examined the long-term efficacy and safety of alirocumab in patients with PCSK9 GoFm and APOB LoFm who participated in the open-label extension to a Phase 2 double-blind study (NCT01604824). Of the 23 patients who completed the 14-week double-blind period and 8-week follow-up, 21 opted to continue in the open-label extension (PCSK9 GoFm, n = 15; APOB LoFm, n = 6).

Long-Term Complications of Open Mason's Vertical Banded Gastroplasty at a Single Tertiary Center and Literature Review.

Vertical banded gastroplasty (VBG), introduced by Mason in 1982, is now discarded because of important long-term complications and technical difficulties to do revisional surgery. We investigated the long-term complications of VBG in our center and compared it with the literature data. Patients who underwent an open VBG at the University Hospital of Nantes between October 1991 and May 2006 were included.

Pharmacokinetic and pharmacodynamic assessment of alirocumab in patients with familial hypercholesterolemia associated with proprotein convertase subtilisin/kexin type 9 gain-of-function or apolipoprotein B loss-of-function mutations.

Background: Familial hypercholesterolemia is characterized by high levels of low-density lipoprotein cholesterol (LDL-C), and causes of familial hypercholesterolemia include apolipoprotein B (APOB) loss-of-function mutations (LOFm) and proprotein convertase subtilisin/kexin type 9 (PCSK9) gain-of-function mutations (GOFm).

Objective: The aim of this study was to compare the pharmacokinetics and pharmacodynamics of alirocumab between patients with APOB LOFm vs PCSK9 GOFm.

Methods: Patients (6 APOB LOFm and 17 PCSK9 GOFm carriers) with LDL-C ≥70 mg/dL on maximally tolerated lipid-lowering therapies received alirocumab 150 mg at Weeks 0, 2, 4, and 6, placebo at Week 8, alirocumab at Week 10, placebo at Weeks 12 and 14, then completed a follow-up period at Week 22.

Elevation of Trimethylamine-N-Oxide in Chronic Kidney Disease: Contribution of Decreased Glomerular Filtration Rate.

Gut microbiota-dependent Trimethylamine-N-oxide (TMAO) has been reported to be strongly linked to renal function and to increased cardiovascular events in the general population and in Chronic Kidney Disease (CKD) patients. Considering the lack of data assessing renal handling of TMAO, we conducted this study to explore renal excretion and mechanisms of accumulation of TMAO during CKD. We prospectively measured glomerular filtration rate (mGFR) with gold standard methods and plasma concentrations of trimethylamine (TMA), TMAO, choline, betaine, and carnitine by LC-MS/MS in 124 controls, CKD, and hemodialysis (HD) patients.