High g-glutamyl-transferase fractions as new markers to identify non-alcoholic fatty liver disease in childhood obesity

The system of advanced glycation end products (AGEs)AGEs and their soluble receptor (sRAGE) could play a role in the development of non-alcoholic fatty liver disease (NAFLD). Recently gamma-glutamyl-transferase (GGT) at values within the normal range, has been associated with evolution of atherosclerotic processes and predicts the onset and outcome of related diseases.The aim of the present study was to determine distinct GGT fractions in obese subjects with and without NAFLD and with serum GGT activity within the high-normal range. Moreover, we try to indentify relationships between the presence of steatosis with ALT, GGT and GGT fractions, hyperlipidemia, and sRAGE.28 obese children and adolescents (20 boys and 8 girls aged 11.9±2.77 years; height SDS 0.55±1.52; BMI SDS 3.11±0.55) were included in the study and were divided in Group 1 (14 with NAFLD) and Group 2 (14 no-NAFLD). Total GGT values were determined by enzyme kinetic assay. Separation of GGT fractions on the basis of their molecular weight was performed through liquid chromatography. sRAGE levels were determined using an ELISA kit.Tryglicerides, GGT, big-GGT (b-GGT), free-GGT (f-GGT) values were significantly higher in Group 1 than in Group 2, while sRAGE levels were significantly lower in Group 1. No other significant difference was found between groups [table1]. A significant negative correlation was demonstrated between sRAGE and GGT (r=-0.49), b-GGT (r=-0.39), small-GGT (s-GGT) (r=-0.47), f-GGT (r=-0.44). GGT activity was positively associated with total cholesterol (r=0.41) and triglycerides (r=0.42); the same significant correlation was demonstrated between the s-GGT fraction and total cholesterol (r=0.44) and triglycerides (r=0.42). f-GGT was the predominant fraction in Group 2, whereas in Group 1 we found a relative increase in s-GGT and b-GGT fractions. In obese NAFLD patients sRAGE significantly and negatively correlates only with s-GGT (r=-0.62).Our data demonstate that definition of specific predictive GGT fraction profile could be used to identify obese children with NAFLD that had higher GGT and lower sRAGE levels than their lean obese counterpart. It is conceivable that s-GGT they may be considered as primary marker of liver injury and as a surrogate for suspected fatty liver. Moreover, the AGEs-RAGE system could play a role in the pathogenesis of NAFLD in childhood obesity.