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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.

Submitted by Lillian Baptistiolli (lillian_bapt@hotmail.com) on 2018-08-21T16:43:36Z No. of bitstreams: 1 TESE LILLIAN BAPTISTIOLLI 2018.pdf: 2912600 bytes, checksum: 8c078031330e745c3443a1523897fef3 (MD5) Approved for entry into archive by Ederson Vasconcelos Pereira null (edersonpereira@fmva.unesp.br) on 2018-08-21T20:13:06Z (GMT) No. of bitstreams: 1 baptistiolli_l_dr_araca_par.pdf: 646086 bytes, checksum: 6ba0ffba750b5d62a88d776f7399e04a (MD5) Made available in DSpace on 2018-08-21T20:13:06Z (GMT). No. of bitstreams: 1 baptistiolli_l_dr_araca_par.pdf: 646086 bytes, checksum: 6ba0ffba750b5d62a88d776f7399e04a (MD5) Previous issue date: 2018-08-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) O Brasil é o segundo maior produtor mundial de carne bovina. Entretanto diversas patologias podem acometer o rebanho bovino e causar significativas perdas econômicas. Diante deste cenário, a infecção por Herpesvirus bovino 5 (BHV5) possui grande importância epidemiológica neste setor, sendo o BHV5 conhecido pelo desenvolvimento de meningoencefalite. Esse vírus possui como características a rápida replicação lítica em cultura de células e a capacidade de estabelecer latência nos gânglios sensoriais do hospedeiro. Assim, essa cepa viral está relacionada à habilidade do BHV5 de invadir, replicar-se no sistema nervoso central (SNC) e causar enfermidade neurológica. É de conhecimento científico que infecções virais estimulam ou inibem a resposta imunológica com objetivo de impedir a replicação e disseminação viral. Entretanto, pouco se sabe sobre o desenvolvimento da resposta imunológica do BHV5 no curso da infecção aguda ou latente. Assim, muitos conceitos sobre a patogênese do BHV5 acabam sendo extrapolados do Herpesvirus bovino 1 (BHV1). Diante deste contexto, faz-se necessário a busca pelo conhecimento da relação entre os vírus e as células de defesa do hospedeiro. Esses achados irão contribuir para um melhor entendimento da patogênese da doença, bem como para o possível desenvolvimento de vacinas mais específicas e eficazes. Brazil is the second largest producer of beef in the world. However several pathologies can affect the bovine herd and cause significant economic losses. In view of this scenario, bovine herpesvirus 5 infection (BHV5) is of great epidemiological importance in this sector, and BHV5 is known for the development of meningoencephalitis. This virus is characterized by rapid lytic replication in cell culture and the ability to establish latency in host sensory ganglia. Thus, this viral strain is related to the ability of BHV5 to invade, replicate in the central nervous system (CNS) and cause neurological disease. It is scientifically known that viral infections stimulate or inhibit the immune response in order to prevent viral replication and dissemination. However little is known about the development of the BHV5 immune response in the course of acute or latent infection. Thus, many concepts about the pathogenesis of BHV5 end up being extrapolated from bovine herpesvirus 1 (BHV1). In this context, it is necessary to search for knowledge about the relationship between viruses and host defense cells. These findings will contribute to a better understanding of the pathogenesis of the disease, as well as to the development of more specific and effective vaccines.

Sertoli cells are crucial for the success of spermatogenesis, which is the biological process that ensures male fertility. These cells present high metabolic rates, being often subjected to high oxidative stress levels that, if uncontrolled, may compromise male fertility. Since the most abundant tea catechin, epigallocatechin-3-gallate (EGCG), has demonstrated a potent preventive activity against oxidative stress, we have evaluated its effect at concentrations of 5 and 50μM, on the metabolism, mitochondrial functionality and oxidative profile of human Sertoli cells (hSCs). While, the highest concentration of EGCG (50μM) increased glucose and pyruvate consumption, it decreased the conversion of pyruvate to alanine to sustain a regular lactate production. However, despite maintaining Krebs cycle functionality, EGCG (50μM) decreased mitochondrial membrane potential of hSCs, which could compromise the normal rates of ATP production. Interestingly, oxidative damages to proteins and lipids decreased in this experimental group, which may be valuable for the nutritional support of spermatogenesis.