Objective: This study was undertaken to investigate the relationship between amino acids (AAs) and nonalcoholic fatty liver disease (NAFLD), and how AAs changed following long-term exercise training under different exercise intensities. Methods: NAFLD participants (n = 220) were recruited and randomly assigned to control, moderate exercise and vigorous exercise groups with a 6-month follow-up. Clinical characteristics were carefully calculated and plasma AAs concentrations were determined using a validated ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. Results: At baseline, AAs concentrations were closely associated with clinical characteristics in NAFLD, particularly, the sum of branched chain amino acids (BCAAs) positively associated with intrahepatic triglyceride (IHTG) content (r = 0.18, p = 0.007). After 6-month exercise intervention, several AAs concentrations altered, and different exercise intensities exerted inverse effects on histidine, serine, glutamine, valine, tyrosine, and tryptophan concentrations changes, particularly, moderate exercise was much more efficient on decreasing BCAAs than vigorous exercise with a significant difference (p = 0.0008). Conclusion: Several AAs was closely associated with IHTG content in NAFLD patients, and 6-month moderate exercise more strongly reduced AAs concentrations, particularly BCAAs, compared to vigorous exercise. These findings suggest that exercise intensity optimization could enhance the metabolic benefits of exercise therapy in NAFLD.

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