Autophagy and mitochondrial damage in the testis of high-fat diet fed rats

High-fat diet (HFD) affects the physiology of reproduction in males, and many studies have investigated its detrimental effects. In this study, we investigated the cellular response induced by an HFD in the rat testis, focusing on the mitochondrial compartment. After five weeks of HFD, an increase in the levels of malondial-dehyde and of reduced form of glutathione in the rat testis indicated an increase in lipid peroxidation. The results showed an increase in autophagy, apoptosis, and mitochondrial damage in the testis of HFD rats. We found a decrease in the protein expression of mitochondrial antioxidant enzymes, such as catalase and SOD2. Immu-nohistochemical analysis revealed a decrease in the immunofluorescent signal of SOD2, mainly in the sper-matogonia and spermatocytes of HFD rats. HFD-induced mitochondrial damage caused a reduction in mitochondria, as evidenced by a decrease in the protein expression of TOM20, a mitochondrial outer membrane receptor. Consistently, HFD enhanced the levels of the PINK1 protein, a mitophagy marker, suggesting the removal of damaged mitochondria under these conditions. Induction of mtDNA damage and repair was stronger in the HFD rat testis. Finally, we found a decrease in the mtDNA copy number and expression of the POLG enzyme, which is involved in mtDNA replication. In conclusion, our results showed that autophagy and apoptosis are activated in the testis of HFD rats as a survival strategy to cope with oxidative stress. Furthermore, HFD-induced oxidative stress affects the mitochondria, inducing mtDNA damage and mtDNA copy number reduc-tion. Mitophagy and mtDNA repair mechanisms might represent a mitochondrial adaptive response.