Efeitos do nonilfenol sobre a massa corporal, adiposidade e homeostase da glicose em camundongos [thesis]

Jamison Cordeiro Dias
AGRADECIMENTOS Agradeço primeiramente a DEUS, por ter colocado pessoas tão especiais em meu caminho, pessoas estas que foram pontuais para a conclusão desse trabalho! Aos meus pais, José Olavo e Maria Guadalupe, que sempre acreditaram em minha capacidade, meu eterno agradecimento. A minha querida esposa, Luiza Karla, por ser tão importante na minha vida. Sempre ao meu lado, me incentivando e me fazendo acreditar que posso mais que imagino. Devido ao seu companheirismo, amizade, paciência,
more » ... ensão, apoio, alegria e amor, este trabalho pôde ser concretizado. Você também faz parte dessa conquista. A minha filha Marry Hillary, que mesmo distante, me incentiva e me enche de orgulho. Aos meus irmãos Henrique, Lidiana, Fabrícia, Geisiane, Igor e Pakollo, meus sinceros agradecimentos. Ao meu grande amigo (in memorian), Vitor Mancilha, um exemplo de superação e esperança. À Profa. Dr.ª Angélica Amorim Amato (UnB -Farmol), minha orientadora, um verdadeiro exemplo de profissional, sempre comprometida em perpetuar o conhecimento, compartilhando-o de forma brilhante e exponencial. À Profa. Dr.ª Michella Coelho, minha co-orientadora, muito obrigada pela ajuda, ensinamentos, orientações e contribuições. Por sempre estar à disposição, respondendo minhas dúvidas e me ensinando conhecimentos essenciais para a realização desse trabalho. Quero deixar meus agradecimentos a Fernanda, que desde o início me ajudou muito em tudo. A Carol, parceira de bancada que contribuiu de forma pontual. Ao meu amigo Camaronês Martin Fonkoua, a todos os estagiários do Farmol, a Glorinha da histologia e as secretarias da pós-graduação. Amigos e professores que pensam de formas tão distintas, enriqueceu significativamente a minha formação. Agradeço a enorme diversidade que me rodeia que, apesar de me desorientar às vezes, me ajuda a captar diferentes olhares sobre o mesmo prisma. A todos os professores do Farmol, obrigado pelos ensinamentos. Palavras-chave: desregulador endócrino; nonilfenol; obesidade; tolerância à glicose. ABSTRACT Nonylphenol (NP) is the result of microbial degradation of alkylphenol ethoxylates (NP) used in manufacturing non-ionic surfactants, emulsifiers, anti-oxidants, detergents, paints, pesticides, herbicides, in addition to being a stabilizer of plastic polymers. Due to the absence of treatment of residues from these industries and of domestic residues, it is widely present in water, including drinkable water. NP is an endocrine disruptor (ED) with well-established estrogenic activity, and its obesogenic potential was recently described in cell culture and in rodent models exposed to NP during the developmental stage. However, the effect of concurrent exposure to NP outside the developmental stage on body weight and metabolic disturbances remains largely unexplored. In this scenario, the aim of this study was to investigate the effect of exposure to NP, since weaning until adult life, on body weight, adiposity and glucose homeostasis in male Swiss mice, and also the effect of exposure limited to adult life on these variables. Twenty mice fed control chow (normolipidic) were randomly assigned into four groups, G1 = control (vehicle), G2 = treatment with NP 0,05 mg/kg/d from the 6 th to the 20 th week of life (from weaning until adult life), G3 = treatment with NP 0,25 mg/kg/d from the 6 th to the 20 th week of life (from weaning until adult life), and G4 = treatment with NP 0,25 mg/kg/d from the 14 th to the 20 th week of life (in adult life). NP was administered in drinking water and the following variables were investigated: body weight, adiposity, glucose homeostasis, energy consumption, water consumption, lipid profile, serum levels of liver enzymes and histological features of adipose tissue and liver. No significant body weight change was seen in response to NP exposure, independently of the dose and the exposure time. However, there was a trend towards weight reduction in all groups exposed to NP, without change in energy consumption. Fasting blood glucose levels assessed at the 14 th and 18 th weeks did not change in response to exposure to NP, although there was an increase in glucose tolerance at the 18 th weeks, after 12 weeks of exposure to 0,25 mg/kg/d of NP. There was no change in insulin sensitivity assessed by insulin tolerance test, and there was also no change in lipid profile or serum levels of liver enzymes. Mice exposed to the higher dose of NP (G3 and G4) exhibited a decrease in inguinal adipose mass and an increase in adipocyte diameter at this depot. There was also an increase in lipid accumulation in the liver and interescapular brown adipose tissue. Kidney or heart mass did not chance in response to exposure no NP. The findings from the present study suggest that chronic exposure to NP, since weaning, does not have an obesogenic effect and that it may even improve glucose tolerance without changing insulin sensitivity in mice fed a control diet, although increasing lipid accumulation in key sites of insulin action.
doi:10.26512/2015.12.d.20120 fatcat:72gukqndtveonikd2agtozvfji