Núria Amigó | Universitat Rovira i Virgili (original) (raw)

Papers by Núria Amigó

Zenodo (CERN European Organization for Nuclear Research), Jul 24, 2023

Medicina clínica, Feb 1, 2024

Antioxidants, Dec 14, 2023

Clinical Metabolomics Applications in Genetic Diseases

Clínica e Investigación en Arteriosclerosis, Jun 1, 2023

Revista Espanola De Cardiologia, Nov 1, 2022

Atherosclerosis, Sep 1, 2016

Objectives: The ATP-binding cassette transporter 1 (ABCA1) is a membrane protein well known for i... more Objectives: The ATP-binding cassette transporter 1 (ABCA1) is a membrane protein well known for its role in cholesterol efflux and HDL formation. Recently, ABCA1 has been implicated as playing a key role in other processes, such as insulin secretion and inflammatory response. We sought to further investigate these potential roles through a quantitative proteomics approach. Specifically, we hypothesized that we could detect differential protein signatures in the plasma of Tangier patients that correspond to pathways involved in diabetes and inflammation. Methods: We used SOMAscan® technology (SomaLogic, Boulder, CO, USA) to analyze plasma collected from 5 Tangier disease patients (homozygotes or compound heterozygotes for functional ABCA1 mutations) and 7 normolipidemic controls. We tested for differences in the levels of approximately 1,000 plasma proteins using a nonparametric test (KS). We then performed Ingenuity Canonical Pathway analysis to examine if proteins linked to diabetes and inflammation pathways were significantly more likely to be differentially abundant in the plasma. We corroborated the results using Gene Set Enrichment Analysis (GSEA). Results: We found an enrichment in differentially abundant proteins involved in type II diabetes mellitus signaling (p-value¼0.0002) and inflammatory pathways, such as granulocyte adhesion and diapedesis (p-value¼2.2*10-12). These results were also corroborated by GSEA, where gene sets corresponding to GO biological processes such as immune response (p-value¼0.008) and inflammatory response (p-value¼0.032) ranked at the top of the enrichment results. Conclusions: The results from this pilot study support the concept that ABCA1 is implicated in pathways affecting immune and inflammatory response and type II diabetes.

Neurogastroenterology and Motility, Aug 13, 2018

Meal ingestion induces a biological response that involves a switch in the activity of the digest... more Meal ingestion induces a biological response that involves a switch in the activity of the digestive system and the perception of sensations, such as satiation and fullness, involved in the homeostatic control of food consumption. 1,2 Both the functional activation and the homeostatic sensations are related to the meal load, eg, the degree of gastric accommodation to the meal and the sensation of satiation and fullness are scaled to the volume ingested. 3-5 The biological response to meal ingestion also involves a hedonic dimension with postprandial satisfaction and a lift in mood. In contrast to the homeostatic responses, the hedonic component of the

Journal of Clinical Medicine, Nov 3, 2019

Renal complications are the major cause of morbidity and mortality in patients with familial leci... more Renal complications are the major cause of morbidity and mortality in patients with familial lecithin-cholesterol acyltransferase (LCAT) deficiency (FLD). We report three FLD patients, two of them siblings-only one of whom developed renal disease-and the third case being a young man with early renal disease. The aim of this study was to analyze the clinical characteristics and possible mechanisms associated with renal disease in these patients. Plasma lipid levels, LCAT activity, lipoprotein particle profile by NMR and FPLC, free and esterified cholesterol, presence of lipoprotein X (LpX) and DNA sequencing in the three FLD patients have been determined. The three cases presented clinical characteristics of FLD, although only one of the siblings developed renal disease, at 45 years of age, while the other patient developed the disease in his youth. Genetic analysis revealed new missense homozygous mutations, p.(Ile202Thr) in both siblings and p.(Arg171Glu) in the other patient. Lipoprotein particle analysis showed that the two patients with renal disease presented higher numbers of small very low-density lipoprotein (VLDL) and a higher concentration of triglycerides in VLDL. This study reports three new cases of LCAT deficiency, not previously described. Renal disease is not only dependent on LCAT deficiency, and could be due to the presence of VLDL particles, which are rich in triglycerides, free cholesterol and LpX.

Scientific Reports, Sep 11, 2018

Fetal growth may be impaired by poor placental function or maternal conditions, each of which can... more Fetal growth may be impaired by poor placental function or maternal conditions, each of which can influence the transfer of nutrients and oxygen from the mother to the developing fetus. Large-scale studies of metabolites (metabolomics) are key to understand cellular metabolism and pathophysiology of human conditions. Herein, maternal and cord blood plasma samples were used for NMR-based metabolic fingerprinting and profiling, including analysis of the enrichment of circulating lipid classes and subclasses, as well as the number of sub-fraction particles and their size. Changes in phosphatidylcholines and glycoproteins were prominent in growth-restricted fetuses indicating significant alterations in their abundance and biophysical properties. Lipoprotein profiles showed significantly lower plasma concentrations of cholesterol-intermediate density lipoprotein (IDL), triglycerides-IDL and high-density lipoprotein (HDL) in mothers of growth-restricted fetuses compared to controls (p < 0.05). In contrast, growth-restricted fetuses had significantly higher plasma concentrations of cholesterol and triglycerides transporting lipoproteins [LDL, IDL, and VLDL, (p < 0.005; all)], as well as increased VLDL particle types (large, medium and small). Significant changes in plasma concentrations of formate, histidine, isoleucine and citrate in growth-restricted fetuses were also observed. Comprehensive metabolic profiling reveals that both, mother and fetuses of pregnancies complicated with fetal growth restriction have a substantial disruption in lipid metabolism. Fetal growth restriction (FGR) affects 6-10% of all pregnancies and is defined as the failure to achieve the genetic growth potential, resulting in a given low birthweight 1. Growth restricted fetuses have a 5 to 10-fold risk of dying in utero, and higher risk of perinatal morbidity and mortality 2,3. In addition, fetuses with growth restriction show metabolic and cardiovascular adaptations that are thought to persist postnatally, with implications for adult disease and repercussions for preventive strategies. A small fraction of the small fetuses diagnosed in utero present as early-onset/severe fetal growth restriction 4. However, the majority of clinical instances of fetal smallness occur late in gestation under two main phenotypes, conventionally defined as small for gestational age (SGA) and FGR 5,6. While the former is usually associated with near-normal perinatal outcomes and are considered

Atherosclerosis, Jul 1, 2015

American Journal of Cardiology, Oct 1, 2022

Clínica E Investigación En Arteriosclerosis (english Edition), Sep 1, 2020

The assessment and prevention of cardiovascular risk (CVR) that persists in patients with dyslipi... more The assessment and prevention of cardiovascular risk (CVR) that persists in patients with dyslipidaemia despite treatment and achievement of goals specific to the plasma concentration of cholesterol linked to low density (c-LDL) is a clinical challenge today, and suggests that conventional lipid biomarkers are insufficient for an accurate assessment of CVR.

European Journal of Clinical Nutrition, May 10, 2017

BACKGROUND/OBJECTIVES: Abnormalities in lipoprotein profiles (size, distribution and concentratio... more BACKGROUND/OBJECTIVES: Abnormalities in lipoprotein profiles (size, distribution and concentration) play an important role in the pathobiology of atherosclerosis and coronary artery disease. Dietary fat, among other factors, has been demonstrated to modulate lipoprotein profiles. We aimed to investigate if background dietary fat (saturated, SFA versus omega-6 polyunsaturated fatty acids, n-6PUFA) was a determinant of the effects of LCn-3PUFA supplementation on lipoprotein profiles. SUBJECTS/METHODS: A randomized controlled clinical intervention trial in a parallel design was conducted. Healthy subjects (n = 26) were supplemented with 400 mg eicosapentaenoic acid plus 2000 mg docosahexaenoic acid daily and randomized to consume diets rich in either SFA or n-6PUFA for a period of 6 weeks. Blood samples, collected at baseline and after 6 weeks of intervention, were assessed for plasma lipoprotein profiles (lipoprotein size, concentration and distribution in subclasses) determined using nuclear magnetic resonance spectroscopy. RESULTS: Study participants receiving the SFA or the n-6PUFA enriched diets consumed similar percentage energy from fat (41 and 42% respectively, P = 0.681). However, subjects on the SFA diet consumed 50% more energy as saturated fat and 77% less as linoleic acid than those consuming the n-6PUFA diet (P o 0.001). The diets rich in SFA and n-6PUFA reduced the concentration of total very-low-density lipoprotein (VLDL) particles (P o0.001, both), and their subclasses and increased VLDL (P = 0.042 and P = 0.007, respectively) and LDL (P = 0.030 and 0.027, respectively) particle size. In addition, plasma triglyceride concentration was significantly reduced by LCn-3PUFA supplementation irrespective of the dietary fat. CONCLUSIONS: LCn-3PUFA modulated lipoprotein profiles in a similar fashion when supplemented in diets rich in either SFA or n-6PUFA.

Clínica e Investigación en Arteriosclerosis, Mar 1, 2016

Background: PCSK9 is a pivotal molecule in the regulation of lipid metabolism. Previous studies h... more 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. Methods: There were recruited a total of 457 patients suffering from T2DM and other metabolic disorders (metabolic syndrome (MetS), obesity and atherogenic dyslipidaemia (AD) and other disorders). Anamnesis, anthropometry and physical examinations were conducted, and vascular and abdominal adiposity imaging were carried out. Biochemical studies were performed to determine PCSK9 plasma levels 6 weeks after lipid lowering drug wash-out in treated patients. A complete metabolomic lipid profile was also generated by NMR. The rs505151 and rs11591147 genetic variants of PCSK9 gene were identified in patients. Results: The results showed that PCSK9 levels are increased in patients with T2DM and MetS (14% and 13%; p < 0.005, respectively). Circulating PCSK9 levels were correlated with an atherogenic lipid profile and with insulin resistance parameters. PCSK9 levels were also positively associated with AD, as defined by lipoprotein particle number and size. The rs11591147 genetic variant resulted in lower levels of circulating PCSK9 and LDL cholesterol (LDL-C). Conclusions: PCSK9 plasma levels are increased in T2DM and MetS patients and are associated with LDL-C and other parameters of AD and glucose metabolism.

Analytical Chemistry, Jan 17, 2018

The structural similarity among lipid species and the low sensitivity and spectral resolution of ... more 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. LipSpin implements a constrained line shape fitting algorithm based on voigt profiles and spectral templates from spectra of lipid standards, which automates the analysis of severely overlapped spectral regions and lipid signals with complex coupling patterns. LipSpin provides the most detailed quantification of fatty acid families and choline phospholipids in serum lipid samples by H NMR to date. Moreover, analytical and clinical results using LipSpin quantifications conform with other techniques commonly used for lipid analysis.

International Journal of Molecular Sciences, Jun 27, 2019

While cholesterol content in high-density lipoproteins (HDLs) is a well-established inverse marke... more 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 1 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. The presence of arteriosclerotic plaques was assessed by ultrasonography. A complete lipoprotein profile was performed by 1 H-NMR (Liposcale test). HDL-TG was strongly positively correlated with total triglycerides, glycerol, and fatty liver index, while a strong negative correlation was observed with HDL-cholesterol (HDL-C) and HDL-particle number (HDL-P). HDL-TG was associated with all triglyceride-rich lipoprotein parameters and had an opposite association with HDL-C and HDL-P. It was also significantly correlated with circulating cholesterol ester transfer protein (CETP). HDL-TG concentrations were higher as metabolic syndrome components increased. HDL-TG was also higher with worsening glucose metabolism. Patients with carotid plaques also showed higher HDL-TG. In contrast to HDL-C, HDL-TG is directly associated with metabolism and arteriosclerotic vascular alterations. HDL-TG should be considered a biomarker of metabolic and cardiovascular risk and could be a marker of HDL dysfunction.

Journal of Clinical Laboratory Analysis, Mar 21, 2020

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial ... more This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.