Department of Microscopy, Laboratory of Cell Biology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira n° 228, 4050-313, Porto, Portugal.
Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313, Porto, Portugal.
Reprod Sci. 2021 Mar;28(3):920-931. doi: 10.1007/s43032-020-00328-x. Epub 2020 Sep 30.
Leptin is an adipose tissue hormone that acts as energy sensor and reproductive function regulator. Recent reports suggest that leptin is involved in mitochondrial biogenesis in different tissue cells. Herein, we hypothesized that leptin could also affect Sertoli cells mitochondrial dynamics and biogenesis. Human Sertoli cells (hSCs) were cultured in the presence of different leptin concentrations (5, 25 and 50 ng/mL) or vehicle for 24 h. The three different leptin concentrations were selected to mimic the circulating levels found either in normal weight, obese, and morbidly obese individuals, respectively. Leptin receptor (LEPR) expression was evaluated as well as mitochondrial membrane potential, complexes levels, complex II activity and basal respiration. Moreover, mitochondrial DNA copy number and expression of mitochondrial biogenesis markers were assessed. In hSCs, leptin concentrations similar to those found both in lean men decreased mitochondrial complex II protein levels, but no changes in its activity were observed. This is in agreement with basal respiration and mitochondrial membrane potential assessments, which indicate no alterations in mitochondrial fitness. Furthermore, no changes in mitochondrial biogenesis markers were observed upon leptin exposure, although SIRT1/3 levels were increased after exposure to the highest leptin concentration. Overall, the increase in SIRT1/3 levels suggests a role for leptin in glycolysis, which given the relevance of SCs glycolytic flux for germ cells nutritional support further reinforces that this mechanism can be linked to obesity-related subfertility/infertility.
瘦素是一种脂肪组织激素，作为能量传感器和生殖功能调节剂。最近的报告表明，瘦素参与不同组织细胞中线粒体生物发生。在此，我们假设瘦素也可能影响支持细胞的线粒体动力学和生物发生。在存在不同瘦素浓度（5、25 和 50ng/mL）或载体的情况下培养人支持细胞（hSCs）24 小时。选择这三种不同的瘦素浓度来模拟分别在正常体重、肥胖和病态肥胖个体中发现的循环水平。评估瘦素受体（LEPR）的表达以及线粒体膜电位、复合物水平、复合物 II 活性和基础呼吸。此外，还评估了线粒体 DNA 拷贝数和线粒体生物发生标志物的表达。在 hSCs 中，与瘦男人中发现的浓度相似的瘦素浓度降低了线粒体复合物 II 蛋白水平，但未观察到其活性发生变化。这与基础呼吸和线粒体膜电位评估一致，表明线粒体适应性没有改变。此外，在暴露于瘦素后未观察到线粒体生物发生标志物的变化，尽管在暴露于最高瘦素浓度后 SIRT1/3 水平增加。总的来说，SIRT1/3 水平的增加表明瘦素在糖酵解中的作用，鉴于 SCs 糖酵解通量对生殖细胞营养支持的重要性，进一步证实了这种机制可能与肥胖相关的生育力/不育有关。
