Efeitos da dieta materna e paterna na programação metabólica da prole com 21 dias até a idade adulta
Data
2022-04-29
Autores
César, Helena de Cássia [UNIFESP]
Orientadores
Pisani, Luciana Pellegrini [UNIFESP]
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: Evidências recentes mostram que tanto a dieta materna quanto a dieta paterna
inadequada estão relacionadas a origem do desenvolvimento de saúde e doença nos
descendentes. Nesse processo, a conexão entre a microbiota intestinal, tecido adiposo e o
sistema nervoso central parece ser um fator fundamental envolvido na programação da
regulação da homeostase energética e consequente desenvolvimento de obesidade.
Objetivo: Avaliar o efeito da dieta materna e paterna, rica em açúcar e gordura - high-fat high sugar (HFS), na programação metabólica com foco na homeostase energética e processo
inflamatório no eixo hipotálamo/cólon e na adiposidade da prole aos 21 e 90 dias de vida.
Material e métodos: Ratos Wistar machos foram tratados por 10 semanas com dieta HFS
ou controle (CD) e acasalados com fêmeas, que receberam HFS ou CD durante a gestação
e a lactação. A prole foi dividida em 4 grupos: (CD) ambos progenitores consumiram CD,
(MH) os pais consumiram CD e as mães consumiram HFS, (PH) os pais consumiram HFS e
as mães consumiram CD, (PMH) ambos progenitores consumiram HFS. Na prole de 21 dias
de machos e fêmeas e machos de 90 dias avaliamos: evolução do peso corporal,
comprimento naso-anal, peso relativo dos órgãos (fígado, cólon e hipotálamo), adiposidade
visceral e parâmetros bioquímicos do soro. Na prole macho de 21 e 90 dias foram avaliados
a concentração de citocinas envolvidas no processo inflamatório no cólon e no hipotálamo;
proteínas da via do TLR4 no hipotálamo; o receptor de insulina hipotalâmica; concentração
sérica de insulina, leptina, LPS, NPY, GLP-1 e grelina; a quantificação de DNA fecal para
Lactobacillus sp. e Bifidobacterium sp.; expressão gênica no cólon e hipotálamo de TLR4,
TNF, MYD88,NFkBp65 e ZO1; expressão gênica no hipotálamo de AgRP, NPY e ObR.
Resultados: Foram encontrados dimorfismos sexuais entre a prole de machos e fêmeas aos
21 dias. A prole de 21 dias de ambos os sexos mostrou aumentada evolução de peso e
adiposidade por efeito de dieta materna HFS. Este efeito permaneceu na prole de machos
até a idade adulta quando ambos os progenitores consumiram HFS, apesar da ingestão de
dieta controle após o desmame pelos descendentes. Na prole de 21 dias, foram encontradas
alterações bioquímicas com influência da dieta materna HFS na prole de machos, e influência
da dieta paterna HFS nos níveis TAG na prole de fêmeas. Na prole macho com 21 dias a
dieta materna teve relação com alterações inflamatórias hipotalâmicas, que parecem estar
associadas à maior adiposidade. Já aos 90 dias houve aumento do fator de transcrição
NFκBp65 no hipotálamo pelo efeito da dieta materna, sugerindo uma predisposição a
inflamação hipotalâmica na idade adulta. A dieta materna e paterna influenciou nos níveis
séricos de NPY na prole de 21 e 90 dias. Na idade adulta, a dieta paterna influenciou nos
níveis séricos reduzidos de grelina e GLP-1. A dieta paterna mostrou ter influência na redução
de ZO1 e aumento de LPS na prole de 21 dias. Tanto a dieta materna quanto a dieta paterna
viii
mostraram influenciar na redução de bactérias das espécies Lactobacillus sp. e
Bifidobacterium sp. aos 90 dias de vida.
Conclusão: A dieta materna e paterna HFS parece influenciar na programação do eixo
intestino-cérebro e hipotálamo-tecido adiposo, levando ao fenótipo de maior adiposidade
visceral e peso na prole de machos no desmame, efeito que permaneceu até a idade adulta.
Introduction: Recent evidence showed that maternal as well as paternal inadequate diets are related to the developmental origins of health and disease in the offspring. In this process, the connection among intestinal microbiota, adipose tissue and central nervous system seems to be a pivotal factor involved in the programming of energy homeostasis regulation and consequently in the development of obesity. Aim: To assess the effect of maternal and paternal diet, high in fat and sugar (HFS), on metabolic programming with a focus on the energy homeostasis and inflammatory process in the hypothalamus/ colon axis and adiposity of 21 and 90-day old offspring. Material and Methods: Male Wistar rats were treated for 10 weeks HFS or control diet (CD) and mated with dams fed HFS or CD during pregnancy and lactation. Groups established: (CD) both parents were fed CD; (MH) paternal intake of CD and maternal intake of HFS; (PH) paternal intake of HFS and maternal intake of CD; (PMH) both parents were fed HFS. In the 21 day old male and female offspring, and 90- day old male offspring were assessed: body weight progress, nasal-anal length, relative organ weights (liver, colon and hypothalamus), visceral adiposity and serum biochemical parameters. In the 21- and 90-day old male offspring we assessed levels of cytokines involved in the inflammatory process in the colon and hypothalamus; proteins involved in the TLR4 pathway in the hypothalamus; insulin receptor levels in the hypothalamus; serum content of insulin, leptin, LPS, NPY, GLP-1 and ghrelin; the quantification of faecal DNA of Lactobacillus sp and Bifidobacterium sp.; colonic and hypothalamic gene expression of TLR4, ZO1, TNF, MYD88 and NFkBp65; hypothalamic gene expression of AgRP, NPY and ObR. Results: Sexual dimorphisms were found between 21-day old female and male offspring. 21- day old offspring of both sexes showed increased body weight progress and adiposity by the effect of maternal HFS diet. This effect in the male offspring lasted until adulthood when both parents were fed HFS, even though offspring ate control diet after weaning. In the 21-day old offspring, serum biochemical alterations were found to be influenced by maternal intake of HFS in male offspring, and paternal HFS diet influence on TAG levels of female offspring. Maternal diet showed to influence alterations in the inflammatory milieu in the hypothalamus of 21-day old male offspring, which seem to be associated with increased adiposity. In the 90- day old male offspring, there was an increase in the transcription factor NFκBp65 in the hypothalamus, suggesting an increased susceptibility to hypothalamic inflammation in the adulthood. Maternal and paternal diet influenced on the NPY serum levels in the 21 and 90- day old offspring. In adulthood, paternal diet influenced on reduced serum levels of ghrelin and GLP-1. Paternal diet showed to have an effect on reduced colonic ZO1 gene expression x and increased serum levels of LPS in the 21-day old offspring. Maternal diet as well as paternal diet showed to influence lower Lactobacillus sp.e Bifidobacterium sp. in the 90-day old offspring Conclusion: Maternal and paternal HFS diet seem to influence on the programming of gutbrain and hypothalamus-adipose tissue axis, leading to the phenotype of increased visceral adiposity and weight of male offspring at weaning, effect that lasted until adulthood.
Introduction: Recent evidence showed that maternal as well as paternal inadequate diets are related to the developmental origins of health and disease in the offspring. In this process, the connection among intestinal microbiota, adipose tissue and central nervous system seems to be a pivotal factor involved in the programming of energy homeostasis regulation and consequently in the development of obesity. Aim: To assess the effect of maternal and paternal diet, high in fat and sugar (HFS), on metabolic programming with a focus on the energy homeostasis and inflammatory process in the hypothalamus/ colon axis and adiposity of 21 and 90-day old offspring. Material and Methods: Male Wistar rats were treated for 10 weeks HFS or control diet (CD) and mated with dams fed HFS or CD during pregnancy and lactation. Groups established: (CD) both parents were fed CD; (MH) paternal intake of CD and maternal intake of HFS; (PH) paternal intake of HFS and maternal intake of CD; (PMH) both parents were fed HFS. In the 21 day old male and female offspring, and 90- day old male offspring were assessed: body weight progress, nasal-anal length, relative organ weights (liver, colon and hypothalamus), visceral adiposity and serum biochemical parameters. In the 21- and 90-day old male offspring we assessed levels of cytokines involved in the inflammatory process in the colon and hypothalamus; proteins involved in the TLR4 pathway in the hypothalamus; insulin receptor levels in the hypothalamus; serum content of insulin, leptin, LPS, NPY, GLP-1 and ghrelin; the quantification of faecal DNA of Lactobacillus sp and Bifidobacterium sp.; colonic and hypothalamic gene expression of TLR4, ZO1, TNF, MYD88 and NFkBp65; hypothalamic gene expression of AgRP, NPY and ObR. Results: Sexual dimorphisms were found between 21-day old female and male offspring. 21- day old offspring of both sexes showed increased body weight progress and adiposity by the effect of maternal HFS diet. This effect in the male offspring lasted until adulthood when both parents were fed HFS, even though offspring ate control diet after weaning. In the 21-day old offspring, serum biochemical alterations were found to be influenced by maternal intake of HFS in male offspring, and paternal HFS diet influence on TAG levels of female offspring. Maternal diet showed to influence alterations in the inflammatory milieu in the hypothalamus of 21-day old male offspring, which seem to be associated with increased adiposity. In the 90- day old male offspring, there was an increase in the transcription factor NFκBp65 in the hypothalamus, suggesting an increased susceptibility to hypothalamic inflammation in the adulthood. Maternal and paternal diet influenced on the NPY serum levels in the 21 and 90- day old offspring. In adulthood, paternal diet influenced on reduced serum levels of ghrelin and GLP-1. Paternal diet showed to have an effect on reduced colonic ZO1 gene expression x and increased serum levels of LPS in the 21-day old offspring. Maternal diet as well as paternal diet showed to influence lower Lactobacillus sp.e Bifidobacterium sp. in the 90-day old offspring Conclusion: Maternal and paternal HFS diet seem to influence on the programming of gutbrain and hypothalamus-adipose tissue axis, leading to the phenotype of increased visceral adiposity and weight of male offspring at weaning, effect that lasted until adulthood.
Descrição
Citação
CÉSAR, Helena de Cássia. Efeitos da dieta materna e paterna na programação metabólica da prole com 21 dias até a idade adulta. 2022. 101 f. Tese (Doutorado Interdisciplinar em Ciências da Saúde) - Instituto de Saúde e Sociedade, Universidade Federal de São Paulo, Santos, 2022.