Efficacy of therapeutic lifestyle changes on lipid profiles assessed by NMR in children with familial and non-familial hypercholesterolemia.

Background And Aims: The first line of therapy in children with hypercholesterolaemia is therapeutic lifestyle changes (TLSC). The efficacy of lifestyle intervention in children with familial hypercholesterolaemia (FH), where LDL-C levels are genetically driven, deserves a focused study.

Aims: To evaluate the impact of a lifestyle education program, focused on food patterns and physical activity, on lipid profiles assessed by nuclear magnetic resonance (NMR) in children with FH vs.

The Circulating GRP78/BiP Is a Marker of Metabolic Diseases and Atherosclerosis: Bringing Endoplasmic Reticulum Stress into the Clinical Scenario.

Background: Glucose-regulated protein 78/Binding immunoglobulin protein (GRP78/BiP) is a protein associated with endoplasmic reticulum stress and is upregulated by metabolic alterations at the tissue-level, such as hypoxia or glucose deprivation, and it is hyper-expressed in fat tissue of obese individuals.

Objective: To investigate the role of the GRP78/BiP level as a metabolic and vascular disease biomarker in patients with type 2 diabetes (DM), obesity and metabolic syndrome (MS).

Methods: Four hundred and five patients were recruited, of whom 52.

Gelsolin: a new biomarker of disease activity in SLE patients associated with HDL-c.

Objectives: To identify potential biomarkers of disease activity analysing the proteome of high-density lipoprotein (HDL) particles from SLE patients in clinical remission and when they develop a flare compared with a healthy control group.

Methods: Quantitative proteomic analyses of purified HDL were performed using Tandem Mass Tag isobaric tag-labelling and nanoLC-Orbitrap (nLC-MS/MS) from nine SLE patients in clinical remission when they developed a flare and from nine healthy controls (9-9-9). We verified the identified proteins by Western blot and ELISA in a cohort of 104 SLE women patients, 46 healthy women and 14 SLE patients when a flare developed.

HDL Triglycerides: A New Marker of Metabolic and Cardiovascular Risk.

While cholesterol content in high-density lipoproteins (HDLs) is a well-established inverse marker of cardiovascular risk, the importance of HDL-triglyceride (HDL-TG) concentration is not well known. We aim to examine plasma HDL-TG concentrations, assessed by H-NMR, in patients with metabolic diseases and their association with classical biomarkers. In this cross-sectional study, we included 502 patients with type 2 diabetes or metabolic syndrome attending the lipid unit of our University Hospital.

Plasma glucose, triglycerides, VLDL, leptin and resistin levels as potential biomarkers for myocardial fat in mice.

Introduction: The increase in myocardial fat has been proposed as one of the main precursors of myocardial dysfunction due to diabetic aetiology, independently of coronary artery disease. However, biomarkers reflecting the myocardial fat content for the clinical detection of this pathology are currently lacking.

Methods: Correlations between cardiac triglyceride content and plasma levels of major altered molecules during diabetes and cardiac mRNA levels of genes involved in cardiac metabolism (Cd36 and Pdk4) have been explored in a murine model of insulin resistance induced by a high-fat diet.

Fatty acid binding protein 4 (FABP4) as a potential biomarker reflecting myocardial lipid storage in type 2 diabetes.

Objective: Fatty acid binding protein 4 (FABP4) is an intracellular lipid chaperone involved in the crosstalk between adipose and peripheral tissues, and it contributes to widespread insulin resistance in cells, including cardiac cells. However, the role of this adipokine in regulating cardiac metabolism and myocardial neutral lipid content in patients with type 2 diabetes has not been elucidated.

Methods: The impact of circulating FABP4 on the cardiac neutral lipid content was measured by proton magnetic resonance spectroscopy (H-MRS) in patients with type 2 diabetes.

Patients With Systemic Lupus Erythematosus Show an Increased Arterial Stiffness That is Predicted by IgM Anti-β -Glycoprotein I and Small Dense High-Density Lipoprotein Particles.

Objective: To investigate the metabolic and immunologic factors associated with the presence of central arterial stiffness as measured by the augmentation index (AIx).

Methods: We conducted a cross-sectional study of 69 female patients with systemic lupus erythematosus (SLE) compared with a control group of 34 healthy women. The anthropometrical variables, the vascular studies, and the analytic data were obtained the same day.

FABP4 inhibitor BMS309403 decreases saturated-fatty-acid-induced endoplasmic reticulum stress-associated inflammation in skeletal muscle by reducing p38 MAPK activation.

Aims: Fatty acid binding protein 4 (FABP4) inhibitors have been proposed as potential therapeutic approaches against insulin resistance-related inflammation and type 2 diabetes mellitus. However, the underlying molecular mechanisms by which these molecules drive these effects in skeletal muscle remain unknown. Here, we assessed whether the FABP4 inhibitor BMS309403 prevented lipid-induced endoplasmic reticulum (ER) stress-associated inflammation in skeletal muscle.

Clinical and pathophysiological evidence supporting the safety of extremely low LDL levels-The zero-LDL hypothesis.

While the impact of very low concentrations of low-density lipoprotein cholesterol (LDL-C) on cardiovascular prevention is very reassuring, it is intriguing to know what effect these extremely low LDL-C concentrations have on lipid homoeostasis. The evidence supporting the safety of extremely low LDL levels comes from genetic studies and clinical drug trials. Individuals with lifelong low LDL levels due to mutations in genes associated with increased LDL-LDL receptor (LDLR) activity reveal no safety issues.

LipSpin: A New Bioinformatics Tool for Quantitative H NMR Lipid Profiling.

The structural similarity among lipid species and the low sensitivity and spectral resolution of nuclear magnetic resonance (NMR) have traditionally hampered the routine use of H NMR lipid profiling of complex biological samples in metabolomics, which remains mostly manual and lacks freely available bioinformatics tools. However, H NMR lipid profiling provides fast quantitative screening of major lipid classes (fatty acids, glycerolipids, phospholipids, and sterols) and some individual species and has been used in several clinical and nutritional studies, leading to improved risk prediction models. In this Article, we present LipSpin, a free and open-source bioinformatics tool for quantitative H NMR lipid profiling.

Plasma inducible degrader of the LDLR, soluble low-density lipoprotein receptor, and proprotein convertase subtilisin/kexin type 9 levels as potential biomarkers of familial hypercholesterolemia in children.

Background: Familial hypercholesterolemia (FH) in children is under-detected. Plasma biomarkers associated with low-density lipoprotein receptor (LDLR) function could help identifying FH children.

Objectives: We aim to assess the clinical value of inducible degrader of the LDLR (IDOL), soluble LDLR (sLDLR), and proprotein convertase subtilisin/kexin type 9 (PCSK9) plasma concentrations in children with FH compared with control children (CCh).

Adipose-Derived Fatty Acid-Binding Proteins Plasma Concentrations Are Increased in Breast Cancer Patients.

Background: Adipose tissue is an endocrine organ that could play a role in tumor progression via its secreted adipokines. The role of adipose-derived fatty acid-binding protein (FABP) 4 and FABP5 in breast cancer is presently under study, but their circulating levels in this pathology are poorly known. We analyzed the blood concentrations of FABP4 and FABP5 in breast cancer patients to determine whether there is an association between them and breast cancer.

Circulating PCSK9 levels and CETP plasma activity are independently associated in patients with metabolic diseases.

Background: PCSK9 inhibition is a new powerful cholesterol-lowering strategy. Recently, it was reported that CETP inhibitors influence PCSK9 levels as an off-target effect. We explored the relationship between circulating PCSK9 levels and CETP activity in patients with metabolic disease who were not on lipid-lowering therapy.

Exogenous FABP4 induces endoplasmic reticulum stress in HepG2 liver cells.

Background And Aims: Fatty acid binding protein 4 (FABP4) is an intracellular fatty acid (FA) carrier protein that is, in part, secreted into circulation. Circulating FABP4 levels are increased in obesity, diabetes and other insulin resistance (IR) diseases. FAs contribute to IR by promoting endoplasmic reticulum stress (ER stress) and altering the insulin signaling pathway.

Impact of epidermal fatty acid binding protein on 2D-NMR-assessed atherogenic dyslipidemia and related disorders.

Background: The role of circulating FABP5 on metabolic alterations is under active evaluation. On the other hand, FABP5 SNPs (rs454550 and rs79370435) seem to modulate its effect.

Objectives: Our aim was to examine the role of circulating FABP5 levels and its main SNPs in atherogenic dyslipidemia (AD) assessed by 2D-Nuclear Magnetic Resonance (NMR) and related metabolic and inflammation markers.

Lipoprotein hydrophobic core lipids are partially extruded to surface in smaller HDL: "Herniated" HDL, a common feature in diabetes.

Recent studies have shown that pharmacological increases in HDL cholesterol concentrations do not necessarily translate into clinical benefits for patients, raising concerns about its predictive value for cardiovascular events. Here we hypothesize that the size-modulated lipid distribution within HDL particles is compromised in metabolic disorders that have abnormal HDL particle sizes, such as type 2 diabetes mellitus (DM2). By using NMR spectroscopy combined with a biochemical volumetric model we determined the size and spatial lipid distribution of HDL subclasses in a cohort of 26 controls and 29 DM2 patients before and after two drug treatments, one with niacin plus laropiprant and another with fenofibrate as an add-on to simvastatin.

Circulating PCSK9 in patients with type 2 diabetes and related metabolic disorders.

Background: PCSK9 is a pivotal molecule in the regulation of lipid metabolism. Previous studies have suggested that PCSK9 expression and its function in LDL receptor regulation could be altered in the context of diabetes. The aim was to assess PCSK9 plasma levels in patients with type 2 diabetes (T2DM) and other related metabolic disorders as well as its relation to the metabolomic profile generated by nuclear magnetic resonance (NMR) and glucose homeostasis.

Body mass index correlates with atherogenic lipoprotein profile even in nonobese, normoglycemic, and normolipidemic healthy men.

Objective: To establish a relationship between body mass index (BMI), lipid, and lipoprotein parameters among nonobese, normoglycemic, and normolipidemic healthy men without any cardiovascular, metabolic, or chronic diseases.

Methods: A total of 297 healthy, nonsmoking males between 20 and 75 years were recruited. Exclusion criteria included familial hypercholesterolemia, any chronic diseases, and BMI ≥ 30 kg/m(2).

New insights into circulating FABP4: Interaction with cytokeratin 1 on endothelial cell membranes.

Fatty acid-binding protein 4 (FABP4) is an adipose tissue-secreted adipokine that is involved in the regulation of energetic metabolism and inflammation. Increased levels of circulating FABP4 have been detected in individuals with cardiovascular risk factors. Recent studies have demonstrated that FABP4 has a direct effect on peripheral tissues, specifically promoting vascular dysfunction; however, its mechanism of action is unknown.

Metabolomics reveals impaired maturation of HDL particles in adolescents with hyperinsulinaemic androgen excess.

Hyperinsulinaemic androgen excess (HIAE) in prepubertal and pubertal girls usually precedes a broader pathological phenotype in adulthood that is associated with anovulatory infertility, metabolic syndrome and type 2 diabetes. The metabolic derangements that determine these long-term health risks remain to be clarified. Here we use NMR and MS-based metabolomics to show that serum levels of methionine sulfoxide in HIAE girls are an indicator of the degree of oxidation of methionine-148 residue in apolipoprotein-A1.

Liposcale: a novel advanced lipoprotein test based on 2D diffusion-ordered 1H NMR spectroscopy.

Determination of lipoprotein particle size and number using advanced lipoprotein tests (ALTs) is of particular importance to improve cardiovascular risk prediction. Here we present the Liposcale test, a novel ALT based on 2D diffusion-ordered (1)H NMR spectroscopy. Our method uses diffusion coefficients to provide a direct measure of the mean particle sizes and numbers.

Remarkable quantitative and qualitative differences in HDL after niacin or fenofibrate therapy in type 2 diabetic patients.

HDL-increasing drugs such as fenofibrate and niacin have failed to decrease the cardiovascular risk in patients with type 2 diabetes. Drug-mediated quantitative and qualitative HDL modifications could be involved in these negative results. To evaluate the quantitative and qualitative effects of niacin and fenofibrate on HDL in patients with type 2 diabetes, a prospective, randomised controlled intervention trial was conducted.

[Interaction of FABP4 with plasma membrane proteins of endothelial cells].

Introduction: Fatty acid binding protein (FABP4) is an adipose tissue-secreted adipokine implicated in the regulation of the energetic metabolism and inflammation. High levels of circulating FABP4 have been described in people with obesity, atherogenic dyslipidemia, diabetes and metabolic syndrome. Recent studies have demonstrated that FABP4 could have a direct effect on peripheral tissues and, specifically, on vascular function.