Metabolomics analysis and modeling suggest a lysophosphocholines-PAF receptor interaction in fibromyalgia

PLoS One. 2014 Sep 19;9(9):e107626. doi: 10.1371/journal.pone.0107626. eCollection 2014.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatography, Liquid
  • Female
  • Fibromyalgia / metabolism*
  • Humans
  • Mass Spectrometry
  • Metabolomics
  • Models, Biological*
  • Molecular Dynamics Simulation
  • Multivariate Analysis
  • Phosphorylcholine / metabolism*
  • Platelet Membrane Glycoproteins / metabolism*
  • Receptors, G-Protein-Coupled / metabolism*


  • Platelet Membrane Glycoproteins
  • Receptors, G-Protein-Coupled
  • platelet activating factor receptor
  • Phosphorylcholine

Grant support

This study was partially supported by the RAS–LR7/2007 [grant number CRP-24879] and University of Cagliari. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.