Influência da mudança na dieta hiperlipídica para uma dieta padrão equilibrada sobre aspectos emocionais e cognitivos em camundongos obesos: estudo da neurotrofina BDNF (Brain Derived Neurotrophic Factor) e do sistema serotoninérgico
Data
2021-10-28
Autores
Ferreira, Nicoly Bédia [UNIFESP]
Orientadores
Mendes-da-Silva, Cristiano [UNIFESP]
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: As dietas obesogênicas, tais como as hiperlipídicas, são caracterizadas pela alta porcentagem de gorduras (principalmente as saturadas) no total de calorias ingeridas por porção e podem desencadear danos à saúde do indivíduo, promovendo alterações metabólicas, cognitivas e comportamentais. Neste contexto, estudos prévios do nosso grupo de pesquisa demonstram que a dieta hiperlipídica pode afetar o sistema neurotransmissor serotoninérgico e a neurotrofina BDNF (brain-derived neurotrophic factor), fatores associados a homeostase energética, regulação do apetite, alterações de memória, depressão e ansiedade. Objetivos: Avaliar a influência na mudança de uma dieta hiperlipídica para uma dieta saudável sobre: peso e composição corporais, comportamentos do tipo ansioso e depressivo, aprendizagem e memória, o sistema serotoninérgico e o fator neurotrófico BDNF no hipocampo e hipotálamo, em camundongos obesos. Metodologia: Camundongos C57BL/6 com idade de 5 semanas, receberam água filtrada e ração padrão comercial ad libitum por 2 semanas (adaptação). Posteriormente, todos receberam uma dieta hiperlipídica (45% das calorias provenientes de lipídios) por 10 semanas para a indução da obesidade. Ao final da 10ª semana, os animais foram divididos aleatoriamente em dois grupos, um permaneceu com a dieta hiperlipídica (DHL, n=10) e o outro iniciou o consumo da dieta padrão (DP, n=10) durante 8 semanas. Após o termino da 8ª semana, ambos os grupos foram submetidos as análises comportamentais, tais como, Teste de Preferência à Sacarose, Labirinto em Cruz Elevado, Campo Aberto, teste de reconhecimento de objetos e teste de Suspensão de Cauda. Posteriormente as análises comportamentais, os animais foram eutanasiados, tecidos adiposos visceral branco, fígado, hipocampo e hipotálamo foram dissecados, sendo estes dois últimos para avaliações da expressão proteica (por Western Blotting) do receptor serotoninérgico 5-HT1A (5-HT1A), da enzima-chave de síntese cerebral de serotonina (5-hidroxitriptamina, 5-HT) triptofano hidroxilase 2 (TPH2) e da neurotrofina BDNF. Resultados: Os achados desse estudo mostram que a DHL utilizada induziu obesidade. Todavia, a mudança para uma dieta padrão nutricionalmente equilibrada foi eficiente para reduzir significativamente os pesos corporal, do tecido adiposo visceral e do fígado nos animais obesos com alteração do padrão alimentar. Ademais, os camundongos obesos que continuaram consumindo DHL apresentaram fenótipo de anedonia, potencial déficit na memória de curto prazo, alterações na locomoção e aumento/tendência de aumento nas expressões do proBDNF e do receptor 5-HT1A, respectivamente, no hipotálamo. Conclusão: A mudança no perfil dietético dos camundongos obesos, de uma DHL para uma dieta padrão/saudável, ao que parece, foi eficiente para alterar a composição corporal e funcionou como fator protetor para a motricidade e memória, contra o desenvolvimento de um comportamento do tipo depressivo e o aumento do percursor do BDNF, que pode atuar como um fator apoptótico no sistema nervoso central.
Introduction: Obesogenic diets, such as high-fat diets (HFDs), showed high percentage of fat (especially saturated) in the total calories ingested per serving and can damage the individual's health, promoting metabolic, cognitive and behavioral changes. In this context, previous studies from our research group demonstrate that HFD can affect the serotoninergic neurotransmitter system and the neurotrophin BDNF (brain-derived neurotrophic factor), factors associated with energy homeostasis, appetite regulation, memory disorders, depression and anxiety. Objective: To evaluate the influence of changing from a HFD to a healthy diet on: body weight and composition, anxious-like and depressive-like behaviors, learning and memory and on the serotonergic system and the neurotrophin BDNF in the hippocampus and hypothalamus, in obese mice. Methodology: C57BL/6 mice, aged 5 weeks, received filtered water and standard commercial chow ad libitum for 2 weeks (adaptation). Subsequently, all received a HFD (45% of calories from lipids) for 10 weeks to induce obesity. At the end of the 10th week, the animals were randomly divided into two groups, one remained on the HFD (HFD, n=10) and the other started to consume the standard diet (SD, n=10) for 8 weeks. After the end of the 8th week, both groups were submitted to several behavioral analyses, such as the Sucrose Preference Test, Elevated plus Maze, Open Field, New Object Recognition and Tail Suspension Test. After all behavioral analyses, the animals were euthanized, white visceral adipose tissue, liver, hippocampus and hypothalamus were dissected, the latter two being for protein expression evaluations (by Western Blotting) of the serotoninergic receptor 5-HT1A (5-HT1A), of the brain synthesis key-enzyme of serotonin (5-hydroxytryptamine, 5-HT) tryptophan hydroxylase 2 (TPH2) and the neurotrophin BDNF. Results: The findings of this study show that the HFD induced obesity. On the other hand, changing to a standard (healthy) diet was effective in significantly reducing body, visceral adipose tissue and liver weights in obese animals with altered dietary patterns. Furthermore, obese mice that continued to consume HFD showed anhedonia phenotype, potential short-term memory deficit, locomotion changes and an increase/trend of increase in proBDNF and 5-HT1A receptor expressions, respectively, in the hypothalamus. Conclusion: The change in the dietary profile of the obese mice, from a DHL to a standard/healthy diet, it seems, was an efficient protective factor for motricity and memory, against the development of a depressive-like behavior and the increase in the BDNF precursor, which can act as an apoptotic factor in the central nervous system.
Introduction: Obesogenic diets, such as high-fat diets (HFDs), showed high percentage of fat (especially saturated) in the total calories ingested per serving and can damage the individual's health, promoting metabolic, cognitive and behavioral changes. In this context, previous studies from our research group demonstrate that HFD can affect the serotoninergic neurotransmitter system and the neurotrophin BDNF (brain-derived neurotrophic factor), factors associated with energy homeostasis, appetite regulation, memory disorders, depression and anxiety. Objective: To evaluate the influence of changing from a HFD to a healthy diet on: body weight and composition, anxious-like and depressive-like behaviors, learning and memory and on the serotonergic system and the neurotrophin BDNF in the hippocampus and hypothalamus, in obese mice. Methodology: C57BL/6 mice, aged 5 weeks, received filtered water and standard commercial chow ad libitum for 2 weeks (adaptation). Subsequently, all received a HFD (45% of calories from lipids) for 10 weeks to induce obesity. At the end of the 10th week, the animals were randomly divided into two groups, one remained on the HFD (HFD, n=10) and the other started to consume the standard diet (SD, n=10) for 8 weeks. After the end of the 8th week, both groups were submitted to several behavioral analyses, such as the Sucrose Preference Test, Elevated plus Maze, Open Field, New Object Recognition and Tail Suspension Test. After all behavioral analyses, the animals were euthanized, white visceral adipose tissue, liver, hippocampus and hypothalamus were dissected, the latter two being for protein expression evaluations (by Western Blotting) of the serotoninergic receptor 5-HT1A (5-HT1A), of the brain synthesis key-enzyme of serotonin (5-hydroxytryptamine, 5-HT) tryptophan hydroxylase 2 (TPH2) and the neurotrophin BDNF. Results: The findings of this study show that the HFD induced obesity. On the other hand, changing to a standard (healthy) diet was effective in significantly reducing body, visceral adipose tissue and liver weights in obese animals with altered dietary patterns. Furthermore, obese mice that continued to consume HFD showed anhedonia phenotype, potential short-term memory deficit, locomotion changes and an increase/trend of increase in proBDNF and 5-HT1A receptor expressions, respectively, in the hypothalamus. Conclusion: The change in the dietary profile of the obese mice, from a DHL to a standard/healthy diet, it seems, was an efficient protective factor for motricity and memory, against the development of a depressive-like behavior and the increase in the BDNF precursor, which can act as an apoptotic factor in the central nervous system.
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Citação
FERREIRA, Nicoly Bédia. Influência da mudança na dieta hiperlipídica para uma dieta padrão equilibrada sobre aspectos emocionais e cognitivos em camundongos obesos: estudo da neurotrofina BDNF (Brain Derived Neurotrophic Factor) e do sistema serotoninérgico. 2021. 65 f. Dissertação (Mestrado Interdisciplinar em Ciências da Saúde) - Instituto de Saúde e Sociedade, Universidade Federal de São Paulo, Santos, 2021.