Table_1_Triglyceride-Rich Lipoproteins and Glycoprotein A and B Assessed by 1H-NMR in Metabolic-Associated Fatty Liver Disease.docx

High plasma triglyceride (TG) levels and chronic inflammation are important factors related to metabolic-associated fatty liver disease in patients at cardiovascular risk. Using nuclear magnetic resonance (¹H-NMR), we aimed to study the triglyceride-rich lipoprotein (TRL) and acute-phase glycoprotein profiles of a cohort of patients with metabolic disease and their relationship with fatty liver. Plasma samples of 280 patients (type 2 diabetes, 81.1%; obesity, 63.3%; and metabolic syndrome, 91.8%) from the University Hospital Lipid Unit were collected for the measurement of small, medium and large TRL particle numbers and sizes and glycoprotein profiles (Glyc-A and Glyc-B) by ¹H-NMR. Liver function parameters, including the fatty liver index (FLI) and fibrosis-4 (FIB-4) score, were assessed. Hepatic echography assessment was performed in 100 patients, and they were followed up for 10 years. TRL particle concentrations showed a strong positive association with Glyc-A and Glyc-B (ρ=0.895 and ρ=0.654, p<0.001, respectively) and with the liver function-related proteins ALT ρ=0.293, p<0.001), AST (ρ=0.318, p<0.001) and GGT (ρ=0.284, p<0.001). Likewise, TRL concentrations showed a positive association with FLI (ρ=0.425, p<0.001) but not with FIB-4. During the follow-up period of 10 years, 18 new cases of steatosis were observed among 64 patients who were disease-free at baseline. Baseline TRL particle numbers and glycoprotein levels were associated with the new development of metabolic-associated fatty liver disease (MAFLD) (AUC=0.692, p=0.018 and AUC=0.669, p=0.037, respectively). Overall, our results indicated that TRL number and acute-phase glycoproteins measured by ¹H-NMR could be potential biomarkers of the development of hepatic steatosis in patients at metabolic risk.