Plasma Metabolomic and Lipidomic Profiling of Metabolic Dysfunction-Associated Fatty Liver Disease in Humans Using an Untargeted Multiplatform Approach
Xiangping Lin,
Xinyu Liu,
Mohamed N. Triba,
Nadia Bouchemal,
Zhicheng Liu,
Douglas I. Walker,
Tony Palama,
Laurence Le Moyec,
Marianne Ziol,
Nada Helmy,
Corinne Vons,
Guowang Xu,
Carina Prip-Buus,
Philippe Savarin
Affiliations
Xiangping Lin
Sorbonne Paris Nord University, Chemistry Structures Properties of Biomaterials and Therapeutic Agents Laboratory (CSPBAT), Nanomédecine Biomarqueurs Détection Team (NBD), The National Center for Scientific Research (CNRS), UMR 7244, 74 Rue Marcel Cachin, CEDEX, 93017 Bobigny, France
Xinyu Liu
CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
Mohamed N. Triba
Sorbonne Paris Nord University, Chemistry Structures Properties of Biomaterials and Therapeutic Agents Laboratory (CSPBAT), Nanomédecine Biomarqueurs Détection Team (NBD), The National Center for Scientific Research (CNRS), UMR 7244, 74 Rue Marcel Cachin, CEDEX, 93017 Bobigny, France
Nadia Bouchemal
Sorbonne Paris Nord University, Chemistry Structures Properties of Biomaterials and Therapeutic Agents Laboratory (CSPBAT), Nanomédecine Biomarqueurs Détection Team (NBD), The National Center for Scientific Research (CNRS), UMR 7244, 74 Rue Marcel Cachin, CEDEX, 93017 Bobigny, France
Zhicheng Liu
School of Pharmacy, Anhui Medical University, Hefei 230032, China
Douglas I. Walker
Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Tony Palama
Sorbonne Paris Nord University, Chemistry Structures Properties of Biomaterials and Therapeutic Agents Laboratory (CSPBAT), Nanomédecine Biomarqueurs Détection Team (NBD), The National Center for Scientific Research (CNRS), UMR 7244, 74 Rue Marcel Cachin, CEDEX, 93017 Bobigny, France
Laurence Le Moyec
Université d’Evry Val d’Essonne—Université Paris-Saclay, 91000 Evry, France
Marianne Ziol
Department of Pathology, University Hospital Jean Verdier, Assistance Publique-Hôpitaux de Paris, 93140 Paris, France
Nada Helmy
Department of Digestive and Metabolic Surgery, Jean Verdier Hospital, Paris XIII University—University Hospitals of Paris Seine Saint-Denis, 93140 Paris, France
Corinne Vons
Department of Digestive and Metabolic Surgery, Jean Verdier Hospital, Paris XIII University—University Hospitals of Paris Seine Saint-Denis, 93140 Paris, France
Guowang Xu
CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
Carina Prip-Buus
Université Paris Cité, CNRS, INSERM, Institut Cochin, 75014 Paris, France
Philippe Savarin
Sorbonne Paris Nord University, Chemistry Structures Properties of Biomaterials and Therapeutic Agents Laboratory (CSPBAT), Nanomédecine Biomarqueurs Détection Team (NBD), The National Center for Scientific Research (CNRS), UMR 7244, 74 Rue Marcel Cachin, CEDEX, 93017 Bobigny, France
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a complex disorder that is implicated in dysregulations in multiple biological pathways, orchestrated by interactions between genetic predisposition, metabolic syndromes and environmental factors. The limited knowledge of its pathogenesis is one of the bottlenecks in the development of prognostic and therapeutic options for MAFLD. Moreover, the extent to which metabolic pathways are altered due to ongoing hepatic steatosis, inflammation and fibrosis and subsequent liver damage remains unclear. To uncover potential MAFLD pathogenesis in humans, we employed an untargeted nuclear magnetic resonance (NMR) spectroscopy- and high-resolution mass spectrometry (HRMS)-based multiplatform approach combined with a computational multiblock omics framework to characterize the plasma metabolomes and lipidomes of obese patients without (n = 19) or with liver biopsy confirmed MAFLD (n = 63). Metabolite features associated with MAFLD were identified using a metabolome-wide association study pipeline that tested for the relationships between feature responses and MAFLD. A metabolic pathway enrichment analysis revealed 16 pathways associated with MAFLD and highlighted pathway changes, including amino acid metabolism, bile acid metabolism, carnitine shuttle, fatty acid metabolism, glycerophospholipid metabolism, arachidonic acid metabolism and steroid metabolism. These results suggested that there were alterations in energy metabolism, specifically amino acid and lipid metabolism, and pointed to the pathways being implicated in alerted liver function, mitochondrial dysfunctions and immune system disorders, which have previously been linked to MAFLD in human and animal studies. Together, this study revealed specific metabolic alterations associated with MAFLD and supported the idea that MAFLD is fundamentally a metabolism-related disorder, thereby providing new perspectives for diagnostic and therapeutic strategies.
