Moreira 2017 MiP2017

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Bruno Moreira
Leptin role in Sertoli cells mitochondria – a novel mechanism with possible implications in the male reproductive potential of obese individuals.

Link: MiP2017

Moreira BP, Martins AD, Monteiro MP, Sousa M, Oliveira PF, Alves MG (2017)

Event: MiP2017

COST Action MITOEAGLE

Metabolic diseases such as obesity have been on the rise during the last decades, reaching worrying levels. Several statistics point towards an even worse future, where several European countries are expected to reach 70% of obese population, in the next 15 years. Obesity is characterized by an abnormal accumulation of fat and is associated with other co-morbidities, such as diabetes. Several causes are appointed for this vertiginous increase including sedentarism and an increased intake of energy-dense foods rich in carbohydrates. Following an inverse trend, fertility rates and sperm parameters of reproductive-aged men are decreasing, evidencing a relationship between both events. In fact, reproductive function is sensitive to energy balance; however, the molecular mechanisms that associate obesity and reproductive dysfunction are still undisclosed [1]. Leptin, an adipocyte-derived hormone, is upregulated in overweight and obese individuals [2]. Besides the well-described actions in the hypothalamus, leptin has important actions in several peripheral tissues. However, despite the focus in leptin during the last two decades, its role in testicular cells is still undisclosed. Recently, our group has identified the leptin receptor in human Sertoli cells (SCs) and demonstrated that leptin modulates human SCs glycolytic profile [3]. Furthermore, several studies have reported leptin’s ability to modulate mitochondrial biogenesis and dynamics [4].

In this study, we studied the potential role of leptin in mitochondrial dynamics and biogenesis in rat and human SCs. SerW3, a rat Sertoli cell line, and Clonetics™ human SCs cultures were established. Once rat SCs reached 80% confluence, they were divided in 4 different groups and incubated with different leptin concentrations during 24h. One group was treated with Sertoli cell medium without addition of leptin while the other groups were treated with 3 different leptin concentrations (5 ng/mL – normal plasmatic concentration, 25 ng/mL –concentration found in obese individuals and 50 ng/mL – supraphysiological concentration). This procedure was repeated for human SCs. In human SCs the concentration of 50 ng/mL mimics the levels found in morbidly obese individuals. Afterwards, cells were tested for mitochondrial membrane potential (JC-1 assay), protein expression of mitochondrial complexes (Western blot) and expression of genes involved in mitochondrial biogenesis (qPCR).

Our results suggest that leptin modulates mitochondrial membrane potential in a concentration of 50 ng/mL in rat SCs. Leptin exposure had no effect in levels of mitochondrial complexes and mRNA levels of mitochondrial biogenesis markers in these cells (Fig. 1). In human SCs, protein levels of complex II presented changes in the groups treated with 5 and 50 ng/mL. Additionally, mRNA levels of SIRT1 presented changes in the group treated with 50 ng/mL (Fig. 2).

Our results show that high concentrations of leptin, found in morbidly obese individuals, modulate mitochondrial function in rat SCs. This could illustrate a novel mechanism through which leptin affects the male reproductive potential in obese male individuals. Notably, some differences obtained are species-dependent illustrating different responses to leptin exposure from rat and human SCs. These differences, particularly in SIRT1 mRNA levels, could also suggest leptin’s involvement in the metabolic control of spermatogenesis.


Bioblast editor: Kandolf G


Labels: MiParea: mt-Biogenesis;mt-density, Comparative MiP;environmental MiP, Exercise physiology;nutrition;life style, Pharmacology;toxicology  Pathology: Obesity 

Organism: Human  Tissue;cell: Genital 

Enzyme: Complex II;succinate dehydrogenase 




Figures

Moreira figure1 MiP2017.jpg
Moreira figure2 MiP2017.jpg

Affiliations

Moreira BP(1,2,3), Martins AD(2,3), Monteiro MP(3,4), Sousa M(2,3), Oliveira PF(3,5,6), Alves MG(2,3)
  1. Health Sciences Research Center (CICS), Univ Beira Interior, Covilhã, Portugal
  2. Dept Microscopy, Lab Cell Biol, Inst Biomedical Sciences Abel Salazar (ICBAS), Univ Porto, Portugal
  3. Unit Multidisciplinary Research in Biomedicine (UMIB), Inst Biomedical Sciences Abel Salazar (ICBAS), Univ Porto, Portugal
  4. Dept Anatomy, Inst Biomedical Sciences Abel Salazar (ICBAS), Univ Porto, Portugal
  5. Dept Genetics, Fac Medicine, Porto, Portugal
  6. i3S – Inst Investigação Inovação em Saúde, Univ Porto, Portugal. – brunommoreira9@gmail.com

References

  1. Oliveira PF, Sousa M, Silva BM, Monteiro MP, Alves MG (2017) Obesity, energy balance and spermatogenesis. Reproduction 153:173-85.
  2. Alves MG, Jesus TT, Sousa M, Goldberg E, Silva BM, Oliveira PF (2016) Male fertility and obesity: are ghrelin, leptin and glucagon-like peptide-1 pharmacologically relevant? Curr Pharm Des 22:783-91.
  3. Martins AD, Moreira AC, Sa R, Monteiro MP, Sousa M, Carvalho RA, Silva BM, Oliveira PF, Alves MG (2015) Leptin modulates human Sertoli cells acetate production and glycolytic profile: a novel mechanism of obesity-induced male infertility? Biochim Biophys Acta 1852:1824-32.
  4. Blanquer-Rossello MM, Santandreu FM, Oliver J, Roca P, Valle A (2015) Leptin Modulates Mitochondrial Function, Dynamics and Biogenesis in MCF-7 Cells. J Cell Biochem 116:2039-48.