Endocrine Abstracts

Introduction: Non-alcoholic fatty liver disease (NAFLD), defined as excess fat accumulation in the liver, is increasingly prevalent due to obesity. NAFLD may lead to steatohepatitis and eventually cirrhosis. Weight loss, either through diet and exercise or medications such as the glucagon-like peptide-1 agonist liraglutide, improves transaminitis, a marker of NAFLD severity. Visceral obesity is associated with increased plasma levels of the amino acids alanine, phenylalanine, tryptophan and tyrosine¹. The glutamate-serine-glycine (GSG) index (= glutamate/[serine + glycine]), derived from the amino acids glutamate, serine and glycine which are involved in glutathione synthesis, is positively associated with hepatic insulin resistance and with hepatic inflammation on liver biopsy². In this study we compared effects of weight loss from either lifestyle modification or liraglutide therapy on serum transaminases and amino acid profiles.

Methods: Thirty obese (mean age 40.7 ± 9.1 years, BMI 33.2 ± 3.6 kg/m², weight 96.4 ± 15.8 kg) adults with NAFLD and transaminitis (mean ALT 87 ± 34 U/L, AST 48 ± 21 U/L) were randomized to either dieting (decrease by 400 kilocalories/day) plus moderate-intensity exercise (200 minutes/week) to induce ≥5% weight loss (DE group, n = 15), or to liraglutide 3 mg daily therapy (LI group, n = 15) with standard weight loss advice for 12 weeks. We measured serum alanine (ALT) and aspartate (AST) aminotransferases, amino acid profile, and insulin resistance calculated using homeostasis model assessment (HOMA).

Results: At baseline, plasma ALT and AST were positively associated with the GSG index, alanine and tyrosine levels. Both DE and LI groups had significant (P < 0.01) and similar (P > 0.05 between groups) reductions in weight (−3.3 ± 2.9 vs −3.1 ± 1.8 kg respectively), HOMA (–2.96 ± 2.25 vs 2.03 ± 2.11), ALT (−42 ± 34 vs −34 ± 27 U/l) and AST (–23 ± 24 vs −10 ± 15 U/l). GSG decreased in both groups, while alanine, phenylalanine, tyrosine and tryptophan decreased only with liraglutide.

Conclusion: Weight loss by either caloric restriction or liraglutide therapy is linked to reduction in severity of NAFLD, as indicated by decreases in transaminases and the GSG index. Liraglutide is additionally associated with reductions in alanine, phenylalanine, tyrosine and tryptophan, which are indicators of visceral obesity.

References

1. Tochikubo O et al. Weight loss is associated with plasma free amino acid alterations in subjects with metabolic syndrome. Nutritrion and Diabetes 2016 6 e197.

2. Gaggini M et al. Altered amino acid concentrations in NAFLD: impact of obesity and insulin resistance. Hepatology 2018 67 145–158.