Altered amino acid concentrations in NAFLD: Impact of obesity and insulin resistance

Plasma concentrations of amino acids (AA), in particular branched chain (BCAA), are often found increased in non-alcoholic fatty liver disease (NAFLD). However, if this is due to increased muscular protein catabolism, obesity and/or increased insulin resistance (IR) or impaired tissue metabolism is not known. Thus, we evaluated a) if subjects with NAFLD non-obese (NAFLD-NO), compared to obese (NAFLD-Ob) display altered plasma AA compared to controls (CT); b) if AA concentrations are associated to IR and liver histology. Also glutamic acid, serine and glycine concentrations were previously found altered in NAFLD. Since these AA are involved in glutathione synthesis we hypothesized they might be related to the severity of NAFLD. In 44 non-diabetic NAFLD subjects with liver biopsy, (29 NAFLD-NO and 15 NAFLD-Ob) and 20 non-obese CT we measured AA profile by GCMS, HOMA-IR, hepatic IR [Hep-IR=Endogenous Glucose Production x Insulin] and the new GSG-index [glutamate/(serine+glycine)] and tested if they were associated with liver histology. Most AA were increased only in NAFLD-Ob. Only alanine, glutamate, isoleucine and valine, but not leucine, were increased in NAFLD-NO compared to CT. Glutamate, tyrosine and GSG-index were correlated with Hep-IR. GSG-index correlated with liver enzymes, in particular GGT (R = 0.70), independently of BMI. Ballooning and/or inflammation at liver biopsy were associated with increased plasma BCAA and Aromatic-AA, and mildly with GSG-index, while only the new GSG-index was able to discriminate fibrosis F3-4 vs. F0-2 in this cohort.