Endurance Training Alleviates Metabolic-Associated Fatty-Liver Disease (MAFLD)-Related Testicular Impairments via Endoplasmic Reticulum Stress Regulation

Background

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 GRP78-IRE-1α-ATF6 signaling pathway.

Methods

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 the research, thyroid stimulating hormone (TSH), sex hormones (testosterone), tumor necrosis factor-alpha (TNF-a) as well as GRP78, IRE-1α, and AFT6 expression were assessed.

Results

Our results indicated that MAFLD led to significant weight gain, disrupted serum levels of thyroid-stimulating hormone, and impaired sex hormone profile. Additionally, MAFLD triggered ER stress, evidenced by dysregulated expression of genes in the GRP78-IRE-1α-ATF6 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.

Conclusion

Overall, the present study suggests endurance training as a promising treatment strategy for addressing MAFLD and its associated reproductive complications.