Expression of obesity-related genes in testes and sperm of rats subjected to caloric restriction and to GLP-1 administration

• Autor(a) principal: Correia, Ana Catarina Silva
• Data de Publicação: 2021
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/32843
• topic: Caloric restriction; Energy homeostasis; GLP-1 administration; Male reproductive function; Obesity-related genes; Sperm; Testes

Caloric restriction (CR), due to its negative energy balance and GLP-1, for being an incretin, constitute two weight loss protocols that remain poorly investigated, particularly its impact on male reproductive function, whose proper functioning depends on a balanced energy homeostasis. That energy homeostasis has been related to genes linked to energy metabolism control, namely the obesity-related genes (ORGs), such as fat mass and obesity associated (FTO), melanocortin-4 receptor (MC4R), glucosamine-6- phosphate deaminase 2 (GNPDA2) and transmembrane protein 18 (TMEM18). Thus, this project aimed to use an animal model to study the potential of CR and GLP-1 administration in the regulation of those ORGs expression in testes and sperm of Wistar rats and verify if there is an impact on sperm quality. Firstly, we observed that CR promoted a lower weight gain and a decrease in insulin resistance. On the other hand, GLP-1 administration, beyond the expected increase in active GLP-1 levels, did not promote any change in glucose metabolism, hormonal profile and consequently in body weight. Furthermore, CR promoted an increase in sperm head defects, while the GLP-1 administration improved sperm morphology. Regarding the ORGs we observed the presence of FTO, MC4R and TMEM18 transcripts in rat testes and identified those transcripts, for the first time, in rat sperm. Additionally, we identified, for the first time, the presence of GNPDA2 transcripts in rat testes and sperm. The corresponding proteins were also identified in rat testes, being that they all presented distinct cellular locations. CR and GLP-1 administration promoted an increase in the expression of the ORGs in testes, however in spermatozoa the expression was not altered. We also identified the presence of NFE2L2 (encodes for an important antioxidant transcription factor) transcripts in rat testes and sperm and verified that their abundance is increased, in testes, by CR and GLP-1 administration. Then we explored, individually, the role the ORGs at the testicular and sperm levels, namely in the response to CR and GLP-1 administration and we obtained some clues related to the potential involvement of each of the ORGs in the male reproductive function. Overall, we were able to perceive that CR and GLP-1 administration promoted a general association of all ORGs with an improvement in oxidative status both in testes and sperm.