Leptin modulates human Sertoli cells acetate production and glycolytic profile: a novel mechanism of obesity-induced male infertility?

• Tipo: Artigo em Revista Científica Internacional
• Data: 2015

Autores

Martins, AD (Autor) Outra; Moreira, AC (Autor) Outra; Sa, R (Autor) Outra; Monteiro, M (Autor) ICBAS; sousa, m (Autor) ICBAS; Carvalho, RA (Autor) Outra; Silva, BM (Autor) Outra; Oliveira, PF (Autor) ICBAS; Alves, MG (Autor) Outra

Revista

Título: Biochimica et Biophysica Acta - Molecular Basis of Disease

Vol. 1852

Páginas: 1824-1832

ISSN: 0925-4439

Editora: Elsevier

Indexação

ISI Web of Knowledge - 33 Citações

Scopus - 47 Citações

Outras Informações

ID Authenticus: P-00G-CHN

DOI: 10.1016/j.bbadis.2015.06.005

Abstract (EN): Human feeding behavior and lifestyle are gradually being altered, favoring the development of metabolic diseases, particularly type 2 diabetes and obesity. Leptin is produced by the adipose tissue acting as a satiety signal. Its levels have been positively correlated with fat mass and hyperleptinemia has been proposed to negatively affect male reproductive function. Nevertheless, the molecular mechanisms by which this hormone affects male fertility remain unknown. Herein, we hypothesize that leptin acts on human Sertoli cells (hSCs), the "nurse cells" of spermatogenesis, altering their metabolism. To test our hypothesis, hSCs were cultured without or with leptin (5,25 and 50 ng/mL). Leptin receptor was identified by gPCR and Western blot. Protein levels of glucose transporters (GLUT1, GLUT2 and GLUT3), phosphofructokinase, lactate dehydrogenase (LDH) and monocarboxylate transporter 4 (MCT4) were determined by Western Blot. LDH activity was assessed and metabolite production/consumption determined by proton nuclear magnetic resonance. Oxidative damage was evaluated by assessing lipid peroxidation, protein carbonilation and nitration. Our data shows that leptin receptor is expressed in hSCs. The concentration of leptin found in lean, healthy patients, upregulated GLUT2 protein levels and concentrations of leptin found in lean and obese patients increased LDH activity. Of note, all leptin concentrations decreased hSCs acetate production illustrating a novel mechanism for this hormone action. Moreover, our data shows that leptin does not induce or protect hSCs from oxidative damage. We report that this hormone modulates the nutritional support of spermatogenesis, illustrating a novel mechanism that may be linked to obesity-induced male infertility.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 9