Shandong Provincial Hospital, Shandong University, Jinan, China.
Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Shandong Provincial Hospital, Jinan, China.
Front Endocrinol (Lausanne). 2022 Sep 27;13:1021263. doi: 10.3389/fendo.2022.1021263. eCollection 2022.
In recent years, the impact of lipotoxicity on male fertility has received extensive attention, especially on Sertoli cells (SCs). In SCs, energy metabolism is important as disorders of energy metabolism result in infertility eventually. However, the underlying mechanism of lipotoxicity on energy metabolism in SCs remains unknown. Advances in high-throughput metabolomics and lipidomics measurement platforms provide powerful tools to gain insights into complex biological systems. Here, we aimed to explore the potential molecular mechanisms of palmitic acid (PA) regulating energy metabolism in SCs based on metabolomics and lipidomics. The results showed that glucose metabolism-related metabolites were not significantly changed, which suggested that PA treatment had little effect on glucose metabolism and may not influence the normal energy supply from SCs to germ cells. However, fatty acid β-oxidation was inhibited according to accumulation of medium- and long-chain acylcarnitines in cells. In addition, the pool of amino acids and the levels of most individual amino acids involved in the tricarboxylic acid (TCA) cycle were not changed after PA treatment in SCs. Moreover, PA treatment of SCs significantly altered the lipidome, including significant decreases in cardiolipin and glycolipids as well as remarkable increases in ceramide and lysophospholipids, which indicated that mitochondrial function was affected and apoptosis was triggered. The increased apoptosis rate of SCs was verified by elevated protein expression levels of Cleaved Caspase-3 and Bax as well as decreased Bcl-2 protein expression level. Together, these findings indicated that PA may result in mitochondrial dysfunction and increased apoptosis by inhibiting fatty acid β-oxidation of SCs.
近年来，脂毒性对男性生育力的影响受到广泛关注，尤其是对支持细胞（SCs）的影响。在SCs 中，能量代谢很重要，因为能量代谢紊乱最终会导致不育。然而，脂毒性对SCs 能量代谢的潜在机制尚不清楚。高通量代谢组学和脂质组学测量平台的进步为深入了解复杂的生物系统提供了有力的工具。在这里，我们旨在基于代谢组学和脂质组学探索棕榈酸（PA）调节SCs 能量代谢的潜在分子机制。结果表明，葡萄糖代谢相关代谢物没有明显变化，这表明 PA 处理对葡萄糖代谢影响不大，可能不会影响SCs 向生殖细胞正常供应能量。然而，根据细胞内中长链酰基辅酶 A 的积累，脂肪酸β-氧化受到抑制。此外，PA 处理SCs 后，氨基酸池和大多数参与三羧酸（TCA）循环的单个氨基酸的水平没有变化。此外，PA 处理SCs 显著改变了脂质组，包括心磷脂和糖脂的显著减少以及神经酰胺和溶血磷脂的显著增加，这表明线粒体功能受到影响并触发了细胞凋亡。SCs 中Cleaved Caspase-3 和 Bax 蛋白表达水平升高以及 Bcl-2 蛋白表达水平降低证实了 SCs 凋亡率增加。综上所述，这些发现表明 PA 可能通过抑制SCs 的脂肪酸β-氧化导致线粒体功能障碍和细胞凋亡增加。
