Effect of Leptin in Human Sertoli Cells Mitochondrial Physiology
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REPRODUCTIVE ENDOCRINOLOGY: ORIGINAL ARTICLE
Effect of Leptin in Human Sertoli Cells Mitochondrial Physiology Bruno P. Moreira 1,2 & Ana M. Silva 1,2 & Ana D. Martins 1,2 & Mariana P. Monteiro 2,3,4 & Mário Sousa 1,2,5 & Pedro F. Oliveira 6 & Marco G. Alves 1,2 Received: 5 May 2020 / Accepted: 20 September 2020 # Society for Reproductive Investigation 2020
Abstract 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. Keywords Leptin . Male fertility . Mitochondria . Sertoli cells . Spermatogenesis
Introduction * Marco G. Alves [email protected] 1
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
2
Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal
3
Department of Anatomy, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal
4
Obesity & Bariatric Services and Centre for Obesity Research, University College of London Hospitals, UCL, London NW1 2BU, UK
5
Centre for Reproductive Genetics Prof. Alberto Barros, 4100-012 Porto, Portugal
6
Department of Chemistry, QOPNA & LAQV, University of Aveiro, 3810-193 Aveiro, Portugal
Leptin is an adipose tissue hormone with a paramount role in regulating energy homeostasis by influencing several pathways in the
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