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AIM: To investigate the therapeutic effects of lutein against non-alcoholic fatty liver disease(NAFLD) and the related underlying mechanism.METHODS: After 9 d of acclimation to a constant temperature-controlled room(20 ℃-22 ℃) under 12h light/dark cycles,male Sprague-Darley rats were randomly divided into two groups and fed a standard commercial diet(n = 8) or a high-fat diet(HFD)(n = 32) for 10 d.Animals receiving HFD were then randomly divided into 4 groups and administered with 0,12.5,25,or 50 mg/kg(body weight) per day of lutein for the next 45 d.At the end of the experiment,the perinephric and abdominal adipose tissues of the rats were isolated and weighed.Additionally,serum and liver lipid metabolic condition parameters were measured,and liver function and insulin resistance state indexes were assessed.Liver samples were collected and stained with hematoxylin eosin and Oil Red O,and the expression of the key factors related to insulin signaling and lipid metabolism in the liver were detected using Western blot and real-time polymerase chain reaction analyses.RESULTS: Our data showed that after being fed a high-fat diet for 10 d,the rats showed a significant gain in body weight,energy efficiency,and serum total cholesterol(TC) and triglyceride(TG) levels.Lutein supplementation induced fat loss in rats fed a highfat diet,without influencing body weight or energy efficiency,and decreased serum TC and hepatic TC and TG levels.Moreover,lutein supplementation decreased hepatic levels of lipid accumulation and glutamic pyruvic transaminase content,and also improved insulin sensitivity.Lutein administration also increased the expression of key factors in hepatic insulin signaling,such as insulin receptor substrate-2,phosphatidylinositol 3-kinase,and glucose transporter-2 at the gene and protein levels.Furthermore,high-dose lutein increased the expression of peroxisome proliferators activated receptor-α and sirtuin 1,which are associated with lipid metabolism and insulin signaling.CONCLUSION: These results demonstrate that lutein has positive effects on NAFLD via the modulation of hepatic lipid accumulation and insulin resistance.