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

Juan Moreno-Vedia,Enrique Ozcariz,Dídac Llop,Daiana Ibarretxe,Ricardo Rodríguez-Calvo,Angels Pedragosa,Roser Rosales,Josefa Girona,Núria Plana,Lluís Masana,Maribel Lahuerta,María Benavent,Antoni Castro

doi:10.3389/fendo.2021.775677

Abstract

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.

Highlights

Triglycerides (TGs) are important cardiovascular risk factors [1]
Considering the inflammatory status related to metabolic syndrome and hepatic steatosis, we investigated the possible role of glycoproteins A and B in the detection of hepatic disease and their possible predictive capacities over a 10-year follow-up
We cross-sectionally characterized the triglyceride-rich lipoproteins (TRLs) subclass particle number, sorted by size, and the plasma glycoprotein profile measured by 1H-NMR in 280 patients at metabolic risk

Summary

Introduction

Triglycerides (TGs) are important cardiovascular risk factors [1]. These lipids are transported mainly by triglyceride-rich lipoproteins (TRLs), a group of circulating lipoproteins that include chylomicrons (only present postprandially or in pathological conditions), VLDL and their remnants, and IDL. The imbalance between VLDL oversynthesis and the secretion of larger VLDL1 particles in the abovementioned metabolic diseases leads to both ectopic hepatic fat accumulation and higher plasma TG concentrations, leading to fatty liver disease [3, 4]. These metabolic alterations are associated with a low degree of chronic systemic inflammation along with local liver inflammation secondary in part to lipotoxicity. These highly prevalent conditions lead to metabolic-associated fatty liver diseases (MAFLDs), cirrhosis or even liver cancer, among others [5, 6]

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