This study investigated the impact of dietary adenine supplementation on fatty liver development in rats fed a low-arginine diet. The researchers demonstrated that a specific serum amino acid profile, resulting from low-arginine diet, induced triglyceride (TAG) accumulation in hepatocytes. Dietary adenine supplementation completely reversed this effect, restoring hepatic TAG secretion and abolishing hepatic TAG accumulation. A non-linear analysis predicted this inhibition using only serum amino acid concentration data. Alterations in histidine, methionine, and branched-chain amino acid (BCAA) concentrations were key factors in this effect. Modifying methionine or BCAA levels in the low-arginine diet also abolished hepatic TAG accumulation. The study concludes that increased methionine and BCAA levels due to arginine deficiency are causative factors for hepatic TAG accumulation, and adenine disrupts this process by modifying serum amino acid profiles.