BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) involves excessive liver fat accumulation and is closely linked to oxidative stress, which contributes to liver inflammation and damage. This study aimed to evaluate how interventions such as resistance training (RT) and vitamin E supplementation (VES) can modulate markers of NAFLD and key proteins regulating glucose and lipid metabolism, such as C1Q/TNF-related proteins (CTRPs). METHODS: Forty participants with NAFLD (mean age 32.4 +/- 8.2 years) were randomly assigned to one of four groups for 12 weeks: placebo (PLB), VES, PLB plus RT, and VES plus RT. VES was administered at 800 IU/day in a double-blind manner. The RT regimen included eight exercises at 60 to 80% of one-repetition maximum (1RM), with three sets of 8 to 12 repetitions, performed three times per week. Pre- and post-intervention assessments included body composition, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lipid profile, glycemic control, CTRP-2, CTRP-9, and 1RM evaluations. RESULTS: Following the interventions, there was a significant improvement in body composition, lipid profile, glycemic control, and 1RM indices in the exercise groups compared to non-exercise groups (p < 0.05). AST and ALT levels decreased in all groups (p < 0.05) compared to the PLB group. There was also a significant difference between the VES plus RT group and both the VES and PLB plus RT groups (p < 0.05). CTRP-2 and CTRP-9 levels decreased in the exercise groups compared to non-exercise groups (p < 0.05), and their changes showed a marked correlation with body composition, lipid profile, and glycemic control indices (p < 0.05). CONCLUSIONS: This study highlights the benefits of RT on various health parameters among NAFLD patients. While adding VES to RT resulted in greater decreases in aminotransferases, it did not provide further improvements in other variables. Additionally, enhancements in body composition, lipid profile, and glycemic control indices were possibly associated with decreased levels of CTRPs. TRIAL REGISTRATION: Registered retrospectively in the Iranian Registry of Clinical Trials (IRCT20220601055056N1) on December 21, 2023.

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