Endurance Training Alleviates Metabolic-associated Fatty-liver Disease (MAFLD)-related Testicular Impairments via ER Stress Regulation

Metabolic-associated fatty liver disease (MAFLD), the most prevalent liver disorder globally, affects 20–40% of the population and presents significant health challenges. Studies link MAFLD to male reproductive dysfunction, highlighting the need for effective interventions. This study investigates the impact of MAFLD on testicular function and evaluates the protective role of endurance training, with a focus on the PERK-EIF2α-ATF4 signaling pathway. Forty-four rats were allocated into two dietary groups (n = 22 each): a standard diet control group (C) and a high-fat diet supplemented with fructose water group (FL). After 17 weeks, histological analysis confirmed MAFLD development in the FL group, while the control group showed no pathological changes. Each dietary group was further subdivided into sedentary and endurance-trained (T) subgroups (n = 10 per subgroup), resulting in four experimental groups: C, C + T, FL + T, and FL. At the end of research, thyroid hormones (T3, T4, TSH), sex hormones (testosterone, LH, FSH) as well as PERK, EIF2α and AFT4 expression were assessed. Our result indicated that MAFLD led to significant weight gain, disrupted serum levels of thyroid hormones, and impaired sex hormone profiles. Additionally, MAFLD triggered ER stress, evidenced by dysregulated expression of genes in the PERK-EIF2α-ATF4 pathway. Remarkably, endurance training mitigated these adverse effects by normalizing hormonal profiles and restoring the expression of ER stress-related genes. These findings highlight the critical role of ER stress in MAFLD-induced male reproductive dysfunction.