Endocrine Abstracts

Metabolic diseases represent a threatening worldwide epidemic that affects the entire body. It is known that metabolic diseases, namely diabetes, and obesity affect spermatogenesis via suppressing testosterone synthesis, inducing oxidative stress and other changes that lead to decreased male fertility. Glucagon-like peptide 1 (GLP1) receptor agonists, like liraglutide, are pharmacological agents recommended to normalize glucose levels in patients with type 2 diabetes mellitus. Recently, these agonists have been approved for the treatment of obesity to reduce body weight in patients without elevated blood glucose levels. However, the effects of liraglutide on male fertility are not fully understood. The main objective of this study was to understand the effect of liraglutide on the function of Leydig cells (LCs) exposed to conditions of hyperglycemia and normoglycemia. For this purpose, we exposed cell cultures of a LCs (BLTK1 cell line) to increasing concentrations of liraglutide (25, 50 and 100 nM), under conditions of normoglycemia (glucose 5 mM) and hyperglycemia (glucose 22 mM). Cellular viability, proliferation, and ROS production were accessed after 48 h treatment. Mitochondria function was accessed by Seahorse XF Cell Mito Stress assay. We observed that none of the concentrations of liraglutide alter the cell proliferation of LCs or induce cytotoxicity, however it induces an increase in the metabolic viability of cells under normoglycemic conditions. Nonetheless, we also observed an increase in oxidative stress caused by all liraglutide concentrations on 5 mM glucose LCs. In addition, mitochondrial bioenergetics is affected, in which liraglutide decreases basal respiration rate, maximal respiration rate, ATP production and proton leak in LCs exposed to hyperglycemic conditions compared to the group of LCs exposed to 22 mM glucose without exposure to any concentration of liraglutide. In conclusion, these results indicate that liraglutide alters the mitochondrial performance of LCs exposed to high glucose concentrations and increases the metabolic viability of cells in normoglycemia. Since mitochondria are essential for cell bioenergetics and for the steroidogenesis that occurs in LCs, it is extremely important in the future to understand the effect of mitochondrial fitness caused by liraglutide on testosterone production and male fertility.