Untargeted Lipidomics Analysis in Metabolic Dysfunction-Associated Steatohepatitis Associated with Morbid Obesity

Abstract

Background & Aims: Currently, there is a need to identify non-invasive biomarkers for an accurate diagnosis of Metabolic Dysfunction-Associated Steatohepatitis (MASH). Therefore, our aim was to perform untargeted lipidomics to identify the circulating lipid metabolite profile of MASH. Methods: We assessed a liquid chromatography coupled to a mass spectrometer-based untargeted lipidomic assay in serum samples of 216 women with morbid obesity that were stratified according to their hepatic histology into Normal Liver (n = 44), Simple Steatosis (SS, n = 66) and MASH (n = 106). Results: First, we identified a profile of lipid metabolites that are increased in Metabolic Dysfunction-Associated Steatotic Liver Disease, composed of ceramides, triacylglycerols and some phospholipids. Then, we identified that patients with SS have a characteristic profile of increased levels of ceramides, diacylglycerols DG (36:2) and DG (36:4), some triacylglycerols and a few phospholipids such as PC (32:1), PE (38:3), PE (40:6), PI (32:0) and PI (32:1). Later, in MASH patients, we found increased levels of ceramides, deoxycholic acid, a set of triacylglycerols, and some phospholipids such as PC, PE, PI and LPI, while we found decreased levels of the DG (36:0). Finally, we have reported a panel of lipid metabolites that are discriminatory and specific to patients with MASH compared to SS patients, made up of increased levels of 9-HODE some PC and PE, LPI (16:0) and decreased levels of DG (36:0). Conclusions: Our investigation has reported a lipid metabolite profile associated with MASH that could be used as a non-invasive diagnostic tool.