O efeito da administração pós-natal de topiramato na programação metabólica de camundongos submetidos a um protocolo de restrição de crescimento intrauterino

• Ano de defesa: 2018
• Autor(a) principal: Oliveira, Allan Chiaratti de [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Restrição de crescimento intrauterino; Camundongo; Programação metabólica; Adiposidade; Insulina; Leptina
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=6312811; https://repositorio.unifesp.br/handle/11600/52887

Obesity is a public health issue with epidemic proportions. Intrauterine growth restriction negatively impacts immediate neonatal outcome and potentially increases the risk of chronic non-transmissible diseases posteriorly in adult life. Animal models have been used to understand the mechanisms underlining these long-term consequences. The search for strategies that could attenuate the impact of intrauterine growth restriction in latter life health is encouraging. Topiramate is an anticonvulsive drug with metabolic effects akin to those involved in metabolic programming. Intrauterine growth restriction was elicited by protein restriction prior and during gestation in female mice. Pups were treated either with topiramate or the vehicle during the suckling period and were challenged with hyperlipidic hypercaloric diet in adulthood. Protein restriction during gestation was able to reduce 36% the birth weight in the mice offspring, and despite slower catch up growth, equivalent weights were observed in restricted and control, male and female mice, at the time the nutritional challenge was initiated. Male and female offspring presented specific physiologic responses to the hyperlipidic diet. Male control mice presented reduced weight gain and reduced adiposity after the nutritional challenge, with no differences in total cholesterol, triglycerides, glucose, leptin or insulin plasma levels between the groups. In the other hand, female animals presented differential responses in leptin and insulin plasma levels, with no differences in other biochemical parameters and body weight or composition. Expression of genes related to leptin and adiponectin cross-talk between adipose tissue, liver, muscle and hypothalamus, as well as genes involved in the control of energetic metabolism in the hypothalamus was not changed in male mice after hyperlipidic diet. Female restricted mice treated with the vehicle presented reduced Ampk messenger RNA (mRNA) expression in muscle, what was attenuated in the restricted female mice treated with topiramate. Restricted female mice treated with topiramate also presented reduced Adiponectin receptor 2 and increased Pomc mRNA expression in the hypothalamus, along with increased Mch and decreased Pre-pro-orexin mRNA expression. Neonatal topiramate administration may have attenuated the programming effect of intrauterine growth restriction in female mice, leading to a most favorable organization of the hypothalamic circuitry involved in energetic metabolism control and increased leptin and insulin sensibility.