Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Università degli studi della Campania "Luigi Vanvitelli", Caserta, Italy.
Dipartimento di Scienze e Tecnologie, Università degli studi del Sannio, Benevento, Italy.
Gen Comp Endocrinol. 2022 Nov 1;328:114104. doi: 10.1016/j.ygcen.2022.114104. Epub 2022 Aug 13.
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 malondialdehyde 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. Immunohistochemical analysis revealed a decrease in the immunofluorescent signal of SOD2, mainly in the spermatogonia 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 reduction. Mitophagy and mtDNA repair mechanisms might represent a mitochondrial adaptive response.
高脂肪饮食（HFD）会影响男性生殖生理，许多研究已经探讨了其有害影响。在这项研究中，我们研究了 HFD 诱导的大鼠睾丸细胞反应，重点关注线粒体区室。在 HFD 五周后，大鼠睾丸中丙二醛和还原型谷胱甘肽水平的增加表明脂质过氧化增加。结果显示 HFD 大鼠睾丸中的自噬、细胞凋亡和线粒体损伤增加。我们发现线粒体抗氧化酶（如过氧化氢酶和 SOD2）的蛋白表达减少。免疫组织化学分析显示，HFD 大鼠的 SOD2 免疫荧光信号减少，主要在精原细胞和精母细胞中。HFD 诱导的线粒体损伤导致线粒体减少，这可以从 TOM20（一种线粒体外膜受体）的蛋白表达减少得到证明。一致地，HFD 增强了 PINK1 蛋白（一种线粒体自噬标志物）的水平，表明在这些条件下会清除受损的线粒体。HFD 大鼠睾丸中的 mtDNA 损伤和修复诱导更强。最后，我们发现 mtDNA 复制酶 POLG 的 mtDNA 拷贝数和表达减少。总之，我们的结果表明，自噬和细胞凋亡在 HFD 大鼠睾丸中被激活，作为应对氧化应激的生存策略。此外，HFD 诱导的氧化应激会影响线粒体，诱导 mtDNA 损伤和 mtDNA 拷贝数减少。线粒体自噬和 mtDNA 修复机制可能代表一种线粒体适应反应。
