title: Metabolomics analysis and modeling suggest a lysophosphocholines-PAF receptor interaction in fibromyalgia.
abstract: Fibromyalgia Syndrome (FMS) is a chronic disease characterized by widespread pain, and difficult to diagnose and treat. We analyzed the plasma metabolic profile of patients with FMS by using a metabolomics approach combining Liquid Chromatography-Quadrupole-Time Of Flight/Mass Spectrometry (LC-Q-TOF/MS) with multivariate statistical analysis, aiming to discriminate patients and controls. LC-Q-TOF/MS analysis of plasma (FMS patients: n = 22 and controls: n = 21) identified many lipid compounds, mainly lysophosphocholines (lysoPCs), phosphocholines and ceramides. Multivariate statistical analysis was performed to identify the discriminating metabolites. A protein docking and molecular dynamic (MD) study was then performed, using the most discriminating lysoPCs, to validate the binding to Platelet Activating Factor (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine, PAF) Receptor (PAFr). Discriminating metabolites between FMS patients and controls were identified as 1-tetradecanoyl-sn-glycero-3-phosphocholine [PC(14:0/0:0)] and 1-hexadecanoyl-sn-glycero-3-phosphocholine [PC(16:0/0:0)]. MD and docking indicate that the ligands investigated have similar potentialities to activate the PAFr receptor. The application of a metabolomic approach discriminated FMS patients from controls, with an over-representation of PC(14:0/0:0) and PC(16:0/0:0) compounds in the metabolic profiles. These results and the modeling of metabolite-PAFr interaction, allowed us to hypothesize that lipids oxidative fragmentation might generate lysoPCs in abundance, that in turn will act as PAF-like bioactivators. Overall results suggest disease biomarkers and potential therapeutical targets for FMS.
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Caboni
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Liori
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy; Biomedicine Department, CRS4, Cagliari, Italy.
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Santoru
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Shailendra
authors.initials: S
authors.lastname: Asthana
authors.affiliation: Biomedicine Department, CRS4, Cagliari, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Pieroni
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Fais
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Era
authors.affiliation: Department of Medical Sciences "Mario Aresu", University of Cagliari, Cagliari, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Cacace
authors.affiliation: Department of Medical Sciences "Mario Aresu", University of Cagliari, Cagliari, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Ruggiero
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Atzori
mesh_terms: D002853:Chromatography, Liquid; D005260:Female; D005356:Fibromyalgia / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry; D055432:Metabolomics; D008954:Models, Biological; D056004:Molecular Dynamics Simulation; D015999:Multivariate Analysis; D010767:Phosphorylcholine / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D010767:Phosphorylcholine