Obesidade e depressão na pós-menopausa: estudo em ratas dos efeitos da ovariectomia sobre aspectos comportamentais e da regulação central da ingestão alimentar
Data
2015-04-30
Tipo
Tese de doutorado
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Resumo
O presente trabalho teve como objetivo pesquisar os mecanismos moleculares envolvidos na interação obesidade/depressão que se desenvolve na pós-menopausa, enfocando a participação do sistema serotoninérgico e outros mediadores da regulação central da ingestão alimentar, bem como a influência de fatores da dieta sobre estas relações. Aos 2 meses de idade, ratas Wistar tiveram os ovários retirados bilateralmente (Ovx) ou passaram por uma falso-ovariectomia (Sham). Após uma semana de recuperação, os animais foram separados em grupos e alimentados durante 8 semanas com dieta controle (OvxC) ou com dieta hiperlipídica enriquecida com banha de porco (OvxL) ou óleo de peixe (OvxF). Apesar de a ingestão calórica ter sido semelhante entre os grupos, a ovariectomia aumentou o ganho de peso corporal, o que foi intensificado pelo consumo de dieta banha e atenuado pela dieta óleo de peixe. O perfil lipídico sérico, bem como o acúmulo de lipídios no fígado, acompanhou essas mudanças. A retirada dos ovários elevou os níveis séricos de glicose, porém apenas os animais OvxL apresentaram leptinemia e insulinemia alterados. Além disso, a ovariectomia sozinha ou em conjunto com o consumo de dieta banha prejudicou a ação hipofágica da serotonina, enquanto o óleo de peixe demonstrou um efeito protetor, o que foi refletido pela expressão gênica de 5HT1B e 5HT2C no hipotálamo. Ainda, a ovariectomia foi um fator ansiogênico, o que foi igualmente e positivamente modulado pelo consumo de dietas hiperlipídicas. No entanto, as dietas com alto teor de gordura não apresentaram influência sobre a vulnerabilidade à depressão induzida pela ovariectomia e sobre a expressão de genes no hipocampo. Finalmente, as análises de correlação concordaram com os resultados encontrados e demonstraram que influências hormonais e dietéticas alteraram o padrão de associações entre adiposidade corporal, genes e comportamento.
The present study aimed to investigate the molecular mechanisms involved in the interaction obesity/depression that develops after menopause, focusing on the participation of the serotonergic system and other mediators of central regulation of food intake, as well as the influence of dietary factors on these relationships. Two-months-old female Wistar rats had their ovaries removed bilaterally (Ovx) or underwent a false-ovariectomy (Sham). After one week of recovery, the animals were separately into groups and fed for 8 weeks with control diet (OvxC) or a high-fat diet enriched with lard (OvxL) or oil fish (OvxF). Although the similar caloric intake between the groups, ovariectomy increased the body weight gain, which was intensified by lard intake and attenuated by fish oil, which was reflected by 5HT1B and 5HT2C hypothalamic gene expression. Serum lipid profile and hepatic lipid accumulation accompanied these changes. Ovaries removal increased the glucose serum levels, but only OvxL animals showed altered serum levels of leptin and insulin. Furthermore, ovariectomy alone or with high-fat diet intake impaired the serotonin-induced hypophagia, while oil fish showed a protective effect. Moreover, ovariectomy was an anxiogenic factor, which was equally and positively modulated by high-fat diets consumption. However, high-fat diets had no effect on the susceptibility to depression induced by ovariectomy and the hippocampal genes expression. Finally, the correlation analysis agreed with the present findings and demonstrated that hormonal and dietary influences altered the pattern of associations between body fat, genes and behavior.
The present study aimed to investigate the molecular mechanisms involved in the interaction obesity/depression that develops after menopause, focusing on the participation of the serotonergic system and other mediators of central regulation of food intake, as well as the influence of dietary factors on these relationships. Two-months-old female Wistar rats had their ovaries removed bilaterally (Ovx) or underwent a false-ovariectomy (Sham). After one week of recovery, the animals were separately into groups and fed for 8 weeks with control diet (OvxC) or a high-fat diet enriched with lard (OvxL) or oil fish (OvxF). Although the similar caloric intake between the groups, ovariectomy increased the body weight gain, which was intensified by lard intake and attenuated by fish oil, which was reflected by 5HT1B and 5HT2C hypothalamic gene expression. Serum lipid profile and hepatic lipid accumulation accompanied these changes. Ovaries removal increased the glucose serum levels, but only OvxL animals showed altered serum levels of leptin and insulin. Furthermore, ovariectomy alone or with high-fat diet intake impaired the serotonin-induced hypophagia, while oil fish showed a protective effect. Moreover, ovariectomy was an anxiogenic factor, which was equally and positively modulated by high-fat diets consumption. However, high-fat diets had no effect on the susceptibility to depression induced by ovariectomy and the hippocampal genes expression. Finally, the correlation analysis agreed with the present findings and demonstrated that hormonal and dietary influences altered the pattern of associations between body fat, genes and behavior.
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Citação
DORNELLAS, Ana Paula Segantine. Obesidade e depressão na pós-menopausa: estudo em ratas dos efeitos da ovariectomia sobre aspectos comportamentais e da regulação central da ingestão alimentar. 2015. 111 f. Tese (Doutorado em Nutrição) - Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2015.