NAFLD progression is related with plasma pro-oxidative biomarkers rather than liver tissue-measured nitrogen metabolism biomarkers in population with obesity and metabolic syndrome

Abstract Background. The metabolic syndrome (MS) is associated with an increased production of nitrogen metabolites and elevated oxidative stress, which favor the development and progression of non-alcoholic fatty liver disease (NAFLD). Subjects with the phenotype known as metabolically unhealthy obese (MUO) meet most of the MS cardiometabolic risk criteria and show a higher prevalence of NAFLD and fibrosis progression risk, compared to the so-known as metabolically healthy obese (MHO). The present study aimed to explore whether liver-specific biomarkers of nitrogen metabolism and oxidative stress, measured in both plasma and in liver tissue, may relate to NAFLD severity and/or metabolic phenotype. Methods. This observational, cross-sectional study included candidates for bariatric surgery with biopsy-proven NAFLD diagnosis and staging. For comparison, the study population was divided according to NAFLD progression (steatohepatitis F0-F1 vs F2-F4) and metabolic phenotype (MHO vs MUO, based on the MS criteria). Hepatic and plasma concentrations of nitrogen metabolites and oxidative stress biomarkers were determined by enzymatic kinetics assays, ELISA and Griess reaction. Results. The study population consisted of 28 patients with obesity and higher prevalence of dyslipidemia, diabetes mellitus and hypertension. NAFLD progression was related with the metabolic phenotype. According to plasma biomarkers, MUO phenotype was related to higher cardiometabolic risk; while NAFLD severity progression was related to higher Hb A1c and triglycerides. Elevated hepatic concentrations of ammonium, nitrites, arginine and citrulline were found in MUO phenotype, but only higher plasma concentration of MDA was found as specifically related to NAFLD progression. Conclusions. Circulating biomarkers of redox state were selectively related with NAFLD progression, supporting prognostic and therapeutic potential target. Hepatic concentrations of nitrogen metabolism biomarkers may be more related to cardiometabolic risk.