Serum untargeted metabolomics delineates the metabolic status in different subtypes of non-alcoholic fatty liver disease.

Abstract Aims The aim of this study was to identify novel serum metabolites associated with non-alcoholic fatty liver disease (NAFLD), and to explore the metabolic discrepancies between Lean-NAFLD and Obese-NAFLD. Methods Serum samples from patients with NAFLD (n = 161) and healthy participants (n = 149) were collected, and metabolites were analyzed with UPLC-Q-TOF MS/MS. Subgroup analyses were performed to explore the metabolic differences among Lean-NAFLD, Obese-NAFLD and healthy controls Results A total of 24 differentially present metabolites were found between patients with NAFLD and healthy controls. Marked metabolic pathway differences were observed among the NAFLD subtypes, including in fatty acid and amino acid metabolism. Ultimately, five metabolites (prasterone, indoxylsulfuric acid, sebacic acid, arachidonic acid and pregnenolone sulfate) were used to establish a diagnostic model to distinguish patients with NAFLD regardless of Lean- or Obese-NAFLD type. Conclusions This study suggested that significant metabolic differences existed among subtypes of NAFLD, and our model might be useful to distinguish patients with NAFLD. These findings may lay a foundation for the detection and treatment of NAFLD subtypes.