Metabolic dynamics of human Sertoli cells are differentially modulated by physiological and pharmacological concentrations of GLP-1

• Type: Article in International Scientific Journal
• Date: 2019

Authors

Martins, AD (Author) Other; Monteiro, MP (Author) Other; Silva, BM (Author) Other; Barrose, A (Author) Other; Sousa, M (Author) Other; Carvalho, RA (Author) Other; Oliveira, PF (Author) FMUP; Alves, MG (Author) Other

Journal

Title: Toxicology and Applied Pharmacology

Vol. 362

Pages: 1-8

ISSN: 0041-008X

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 25 Citations

Scopus - 32 Citations

Other information

Authenticus ID: P-00P-RBE

DOI: 10.1016/j.taap.2018.10.009

Abstract (EN): Obesity incidence has pandemic proportions and is expected to increase even further. Glucagon-like peptide-1 (GLP-1) based therapies are well-established pharmacological resources for obesity treatment. GLP-1 regulates energy and glucose homeostasis, which are also crucial for spermatogenesis. Herein, we studied the GLP-1 effects in human Sertoli cells (hSCs) metabolism and mitochondrial function. hSCs were cultured in absence or exposed to increasing doses of GLP-1 mimicking physiological post-prandial (0.01 nM) levels or equivalent to pharmacological levels (1 and 100 nM) used for obesity treatment. We identified GLP-1 receptor in hSCs. Consumption/production of extracellular metabolites were assessed, as well as protein levels or activities of glycolysis-related enzymes and transporters. Mitochondrial membrane potential and oxidative damage were evaluated. Glucose consumption decreased, while lactate production increased in hSCs exposed to 0.01 and 1 nM GLP-1. Though lactate dehydrogenase (LDH) protein decreased after exposure to 100 nM GLP-1 its activity increased in hSCs exposed to the same concentration of GLP-1. Mitochondrial membrane potential decreased in hSCs exposed to 100 nM of GLP-1, while formation of carbonyl groups was decreased in those cells. Those effects were followed by an increase in p-mammalian target of rapamycin (mTOR) Ser(2448). Overall, the lowest concentrations of GLP-1 increased the efficiency of glucose conversion to lactate, while GLP-1 concentration of 100 nM induces mTOR phosphorylation, decreases mitochondrial membrane potential and oxidative damage. GLP-1 regulates testicular energy homeostasis and pharmacological use of GLP-1 analogues could be valuable to counteract the negative impact of obesity in male reproductive function.

Language: English

Type (Professor's evaluation): Dissemination

No. of pages: 8