Navik, UmashankerSheth, Vaibhav G.Sharma, NishaTikoo, Kulbhushan2024-01-212024-08-142024-01-212024-08-142022-03-312042649610.1039/d1fo03403khttps://kr.cup.edu.in/handle/32116/4314Recently, the protective effects of a methionine-rich diet on hepatic oxidative stress and fibrosis have been suggested but not adequately studied. We, therefore, hypothesized that l-methionine supplementation would ameliorate the progression of hepatic injury in a diet-induced non-alcoholic steatohepatitis (NASH) model and aimed to investigate the underlying mechanism. NASH was developed in male Sprague Dawley rats by feeding them with a high-fat-fructose diet (HFFrD) for 10 weeks. The results demonstrated that l-methionine supplementation to NASH rats for 16 weeks improved the glycemic, lipid, and liver function profiles in NASH rats. Histological analysis of liver tissue revealed a remarkable improvement in the three classical lesions of NASH: steatosis, inflammation, and ballooning. Besides, l-methionine supplementation ameliorated the HFFrD-induced enhanced lipogenesis and lipid peroxidation. An anti-inflammatory effect of l-methionine was also observed through the inhibition of the release of proinflammatory cytokines. Furthermore, the hepatic SIRT1/AMPK signaling pathway was associated with the beneficial effects of l-methionine. This study demonstrates that l-methionine supplementation in HFFrD-fed rats improves their liver pathology via regulation of lipogenesis, inflammation, and the SIRT1/AMPK pathway, thus encouraging its clinical evaluation for the treatment of NASH. � 2022 The Royal Society of Chemistry.en-USAMP-Activated Protein KinasesAnimalsDiet, High-FatDietary SupplementsDisease Models, AnimalFibrosisFructoseInflammationLipid MetabolismLiverMaleMethionineNon-alcoholic Fatty Liver DiseaseRatsRats, Sprague-DawleySirtuin 1Amino acidsNutritionPathologyRatsfructosehydroxymethylglutaryl coenzyme A reductase kinasemethioninesirtuin 1Hepatic injuryHistological analysisL-methionineLipid metabolismsLipogenesisLiver functionsMethionineNon-alcoholic steatohepatitisProtective effectsSprague-Dawley ratsadverse eventanimaldietary supplementdisease modelfibrosisgeneticsinflammationlipid dietlipid metabolismlivermalemetabolismnonalcoholic fatty liverratSprague Dawley ratFructoseArticlehttp://xlink.rsc.org/?DOI=D1FO03403K