An experimental study on shrimp bioactive peptides restoring testicular function in a rat model of fatty liver disease via autophagy, redox balance, and energy transporters

Background: Non-alcoholic fatty liver disease is a widely prevalent condition in the modern era, with potential adverse effects on fertility and the reproductive system. Objective: This experimental study investigated the adverse effects of non-alcoholic fatty liver disease induced by a high-fat diet (HFD) on testicular structural integrity, with a focus on oxidative stress and metabolic alterations. Materials and Methods: To produce bioactive peptides (HPs), whiteleg shrimp by-products were hydrolyzed using alcalase at 50°C for 3 hr. For this experimental study, 24 male Wistar rats (230 ± 23.1 gr, 8 wk) were randomly assigned to 4 groups (n = 6/each): control (standard diet), HFD-sole, HFD+HP20 (HFD supplemented with 20 mg/kg bodyweight of HPs), and HFD+HP300 (HFD supplemented with 300 mg/kg BW of HPs). After 10 wk of dietary intervention, testicular tissues were subjected to histological, molecular, and oxidative stress analyses. Results: After 70 days, the HFD group showed higher malondialdehyde and glutathione, but a lower glutathione/glutathione disulfide ratio (40%, p < 0.001), indicating reductive stress. HPs, especially at higher doses, alleviated stress, improved seminiferous tubule morphology, and increased tubular differential index and spermiogenesis index indices. Autophagy genes (Beclin1, Atg7, LC3-I, p62) rose in HFD but were downregulated by HPs. Glucose transporter 1, 3 (GLUT-1+, GLUT-3+) and monocarboxylate transporter 4 cell distributions decreased in HFD but were restored in HP-received groups. Conclusion: HPs improved tubular differential index and spermiogenesis index values associated with restored GLUT-1/3 and monocarboxylate transporter 4 expression in Sertoli cells, suggesting that Sertoli cells provided enhanced metabolic support for germ cell development.