Abstract
Preliminary evidence suggests that the glutamate–serine–glycine (GSG) index, which combines three amino acids involved in glutathione synthesis, may be used as a potential biomarker of non-alcoholic fatty liver disease (NAFLD). We investigated whether the GSG index is associated with NAFLD in youth, independent of other risk factors. Intrahepatic fat content (HFF%) and abdominal fat distribution were measured by magnetic resonance imaging (MRI) in a multiethnic cohort of obese adolescents, including Caucasians, African Americans, and Hispanics. NAFLD was defined as HFF% ≥ 5.5%. Plasma amino acids were measured by mass spectrometry. The GSG index was calculated as glutamate/(serine + glycine). The GSG index was higher in NAFLD patients (p = 0.03) and positively correlated with HFF% (r = 0.26, p = 0.02), alanine aminotransferase (r = 0.39, p = 0.0006), and aspartate aminotransferase (r = 0.26, p = 0.03). Adolescents with a high GSG index had a twofold higher prevalence of NAFLD than those with a low GSG index, despite similar adiposity, abdominal fat distribution, and liver insulin resistance. NAFLD prevalence remained significantly different between groups after adjustment for age, sex, race/ethnicity, and body mass index (OR 3.07, 95% confidence interval 1.09–8.61, p = 0.03). This study demonstrates the ability of the GSG index to detect NAFLD in at-risk pediatric populations with different genetically determined susceptibilities to intrahepatic fat accumulation, independent of traditional risk factors.
Highlights
Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide, with an estimated prevalence of 40% in obese youth [1]
No relationships were found between GSG index and age, BMI z-score, markers of glucose control, lipid profile, visceral and subcutaneous fat, branched-chain amino acids (BCAA), and hepatic insulin resistance index (HIRI)
By implementing an accurate magnetic resonance imaging (MRI)-based characterization of abdominal fat distribution, we observed for the first time that the relationship between GSG index and HFF% is independent of overall adiposity and visceral fat, supporting its role as a specific marker of intrahepatic fat content
Summary
Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide, with an estimated prevalence of 40% in obese youth [1]. There is an urgent clinical need for non-invasive, high-throughput diagnostic tools for NAFLD. Metabolomics studies have recently identified specific amino acid patterns that may be used as potential biomarkers of liver disease [2]. Gaggini et al [3] proposed a novel glutamate–serine–glycine (GSG) index, which combines three amino acids involved in glutathione synthesis and hepatic lipotoxicity. GSG index was found to be significantly higher in adults with biopsy-proven NAFLD compared with lean controls and was associated with liver enzymes and hepatic insulin resistance [3]. Two preliminary reports showed that GSG index changes
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