Cardiometabolic Factor-Specific Metabolic Signatures in Metabolic Dysfunction-Associated Steatotic Liver Disease: Insights from Non-Targeted Metabolomics

Abstract

Oxidative stress plays a crucial role in the development of metabolic dysfunction-associated steatotic liver disease (MASLD). Recently, cardiometabolic factors (CMFs) have become essential components of MASLD diagnosis. However, the extent to which individual CMFs contribute to metabolomic alterations in MASLD remains unclear. We aimed to identify associations between CMFs and metabolite levels in patients with MASLD. Serum samples from 31 patients with MASLD and 21 patients without MASLD were subjected to non-targeted metabolomic analysis using liquid chromatography–mass spectrometry. We identified 35 metabolites whose serum levels differed between the non-MASLD and MASLD groups. Of these, 22 metabolites were annotated, including sphingomyelins, phosphatidylcholines, phosphatidylethanolamine, lysophosphatidylcholines, lysophosphatidylethanolamine, plasmalogens, amino acids, a bile acid, and a phenolic compound. Distinct associations were observed between CMFs and metabolite alterations, including obesity and higher glutamic acid levels, diabetes and higher SM(d36:0) and SM(d38:0) levels, and hypertension and lower LPC(18:1) and LPC(18:2) levels. Although several altered metabolites were linked to oxidative stress-related pathways, direct oxidative stress biomarkers were not measured. Thus, the relationship between these metabolite alterations and redox imbalance remains hypothetical and requires further investigation. However, the findings in the present study provide insight into the metabolic mechanisms linking cardiometabolic dysfunction and may facilitate biomarker discovery.