Obesity-Dependent Metabolic Signatures Associated with Nonalcoholic Fatty Liver Disease Progression

• DOI: 10.1021/pr201223p
• Publication Date: 2012-02-24T21:48:10Z
• Authors: J. Barr; J. Caballería; I. Martínez-Arranz; A. Domínguez-Díez; C. Alonso; J. Muntané; M. Pérez-Cormenzana; C. García-Monzón; R. Mayo; A. Martín-Duce; M. Romero-Gómez; O. Lo Iacono; J. Tordjman; R. J. Andrade; M. Pérez-Carreras; Y. Le Marchand-Br...; A. Tran; C. Fernández-Esca...; E. Arévalo; M. García-Unzueta; K. Clement; J. Crespo; P. Gual; M. Gómez-Fleitas; M. L. Martínez-Ch...; A. Castro; S. C. Lu; M. Vázquez-Chantada; J. M. Mato
• Keywords: Steatosis; Metabolome; Steatohepatitis

Our understanding of the mechanisms by which nonalcoholic fatty liver disease (NAFLD) progresses from simple steatosis to steatohepatitis (NASH) is still very limited. Despite growing number studies linking with altered serum metabolite levels, an obstacle development metabolome-based NAFLD predictors has been lack large cohort data biopsy-proven patients matched for key metabolic features such as obesity. We studied 467 biopsied individuals normal histology (n = 90) or diagnosed (steatosis, n 246; NASH, 131), randomly divided into estimation (80% all patients) and validation (20% groups. Qualitative determinations 540 variables were performed using ultraperformance liquid chromatography coupled mass spectrometry (UPLC–MS). The profile was dependent on patient body-mass index (BMI), suggesting that pathogenesis mechanism may be quite different depending individual’s level A BMI-stratified multivariate model based used separate without NASH. area under receiver operating characteristic curve 0.87 in 0.85 group. cutoff (0.54) corresponding maximum average diagnostic accuracy (0.82) predicted NASH a sensitivity 0.71 specificity 0.92 (negative/positive predictive values 0.82/0.84). present data, indicating BMI-dependent able reliably distinguish patients, have significant implications biomarkers potential novel targets therapeutic intervention.