Restrição calórica materna no último terço gestacional e as consequências de curto e longo prazo sobre o metabolismo da prole

Detalhes bibliográficos
Autor(a) principal: Parrela, Jocemara Patricia Silva de Souza
Data de Publicação: 2021
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFMT
Texto Completo: http://ri.ufmt.br/handle/1/5771
Resumo: Intrauterine malnutrition at critical stages of development increases the vulnerability to metabolic diseases in adult life. The present study aimed to evaluate the effects of calorie restriction in the last third of gestation, on biometric, biochemical, molecular and functional parameters of just weaned and adult rat offspring, as well as on biochemical parameters of breast milk. Female Wistar rats were submitted to food restriction (50%) during the last third of gestation (FR50 group), while control rats were fed ad libitum throughout pregnancy (CONT group). At birth, the birthweight, number of livebirths, naso-anus length and sex of pups were assessed, as well as the litter size adjusted to 8 pups/mother. On the 6th, 11th and 16th day of lactation, milk intake was quantified. On the 12th day of lactation, a milk sample was taken to evaluate the energy content, biochemical parameters. On the 22nd day of age, weaning was performed, where a half of rat offspring was euthanized for tissue removal (white and brown adipose tissue and hypothalamus) for biometric and molecular analysis, and blood collected for biochemical analysis (glycemia, lipid and metabolic hormonal profile). In addition, mothers were euthanized for blood collection and subsequent biochemical analysis. The other half of rat offspring was kept into adulthood. Body weight and food intake were measured every two days. At 90 days of age, individual food intake in the dark cycle was evaluated. At 100 days of age, rat offspring were euthanized to collect blood, fat stores and skeletal muscle for biochemical and biometric analysis, and thoracic aorta removed and isolated to assess vascular reactivity. In relation to CONT mothers, milk from FR50 mothers display higher energy content (22%; P<0.05). It was richer in glucose (27%; P<0.01), total cholesterol (41%; P<0.05), triglycerides (2%; P<0.05), as well as with changes in the metabolic hormone values, rich in acylated ghrelin (70%; P<0.05) and poor in leptin (78%; P<0.001) and corticosterone (14%; P<0.05). Compared to CONT mothers, FR50 rats presented hypoglycemia (23%, P<0.001) and increased values of triglyceride (38%; P<0.01) and VLDL cholesterol (38%; P<0.01) and leptin (155%; P<0.001) without changes in acylated ghrelin and corticosterone levels. The FR50 rat offspring, compared to CONT rats, were born with small naso-anus length and body weight (P<0.001). During lactation, the evolution of body weight and milk intake in the FR50 group were higher compared to the CONT group (P<0.001). At weaning, FR50 rat offspring presented obese phenotype (P<0.001), hyperglycemia, insulin resistance and dyslipidemia (P<0.05), hyperghrelinemia (64%; P<0.05) and hyperleptinemia (82%; P<0.01), as well as up regulation of hypothalamic ghrelin receptor (~4-fold, P<0.01), when compared to CONT. Regarding data in adulthood, FR50 rats presented obese phenotype (P<0.05), hyperglycemia (12%; P<0.001), hypertriglyceridemia (16%; P<0.01), insulin resistance (+3%; P<0.001), dyslipidemia (P<0.05) and high Castelli I (+46%; P<0.01) and II (+59%; P<0.01) indices; as well as dysfunction in the vascular contractile response in the thoracic aorta (P<0.01). We conclude that malnutrition in the last third of gestation promotes changes in the biochemical, energetic and in the metabolic hormones composition in breast milk, possibly contributing to the programming of obese phenotype of rat offspring in childhood, which suggest a relation with hyperphagia and greater amount of ghrelin receptor in hypothalamus at this stage of development. In addition, it is summarized that the obese and dyslipidemic phenotype extend throughout life, and that FR50 rats are more likely to develop cardiovascular diseases.
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spelling Restrição calórica materna no último terço gestacional e as consequências de curto e longo prazo sobre o metabolismo da proleProgramação cardiometabólicaDesnutrição intrauterinaLeptinaGrelinaObesidadeCNPQ::CIENCIAS DA SAUDE::MEDICINACardiometabolic programmingIntrauterine malnutritionLeptinGhrelinObesityIntrauterine malnutrition at critical stages of development increases the vulnerability to metabolic diseases in adult life. The present study aimed to evaluate the effects of calorie restriction in the last third of gestation, on biometric, biochemical, molecular and functional parameters of just weaned and adult rat offspring, as well as on biochemical parameters of breast milk. Female Wistar rats were submitted to food restriction (50%) during the last third of gestation (FR50 group), while control rats were fed ad libitum throughout pregnancy (CONT group). At birth, the birthweight, number of livebirths, naso-anus length and sex of pups were assessed, as well as the litter size adjusted to 8 pups/mother. On the 6th, 11th and 16th day of lactation, milk intake was quantified. On the 12th day of lactation, a milk sample was taken to evaluate the energy content, biochemical parameters. On the 22nd day of age, weaning was performed, where a half of rat offspring was euthanized for tissue removal (white and brown adipose tissue and hypothalamus) for biometric and molecular analysis, and blood collected for biochemical analysis (glycemia, lipid and metabolic hormonal profile). In addition, mothers were euthanized for blood collection and subsequent biochemical analysis. The other half of rat offspring was kept into adulthood. Body weight and food intake were measured every two days. At 90 days of age, individual food intake in the dark cycle was evaluated. At 100 days of age, rat offspring were euthanized to collect blood, fat stores and skeletal muscle for biochemical and biometric analysis, and thoracic aorta removed and isolated to assess vascular reactivity. In relation to CONT mothers, milk from FR50 mothers display higher energy content (22%; P<0.05). It was richer in glucose (27%; P<0.01), total cholesterol (41%; P<0.05), triglycerides (2%; P<0.05), as well as with changes in the metabolic hormone values, rich in acylated ghrelin (70%; P<0.05) and poor in leptin (78%; P<0.001) and corticosterone (14%; P<0.05). Compared to CONT mothers, FR50 rats presented hypoglycemia (23%, P<0.001) and increased values of triglyceride (38%; P<0.01) and VLDL cholesterol (38%; P<0.01) and leptin (155%; P<0.001) without changes in acylated ghrelin and corticosterone levels. The FR50 rat offspring, compared to CONT rats, were born with small naso-anus length and body weight (P<0.001). During lactation, the evolution of body weight and milk intake in the FR50 group were higher compared to the CONT group (P<0.001). At weaning, FR50 rat offspring presented obese phenotype (P<0.001), hyperglycemia, insulin resistance and dyslipidemia (P<0.05), hyperghrelinemia (64%; P<0.05) and hyperleptinemia (82%; P<0.01), as well as up regulation of hypothalamic ghrelin receptor (~4-fold, P<0.01), when compared to CONT. Regarding data in adulthood, FR50 rats presented obese phenotype (P<0.05), hyperglycemia (12%; P<0.001), hypertriglyceridemia (16%; P<0.01), insulin resistance (+3%; P<0.001), dyslipidemia (P<0.05) and high Castelli I (+46%; P<0.01) and II (+59%; P<0.01) indices; as well as dysfunction in the vascular contractile response in the thoracic aorta (P<0.01). We conclude that malnutrition in the last third of gestation promotes changes in the biochemical, energetic and in the metabolic hormones composition in breast milk, possibly contributing to the programming of obese phenotype of rat offspring in childhood, which suggest a relation with hyperphagia and greater amount of ghrelin receptor in hypothalamus at this stage of development. In addition, it is summarized that the obese and dyslipidemic phenotype extend throughout life, and that FR50 rats are more likely to develop cardiovascular diseases.A desnutrição intrauterina em estágios críticos do desenvolvimento, deixa alta vulnerabilidade ao aparecimento de doenças metabólicas durante o percurso da vida. No presente estudo objetivamos avaliar o efeito da restrição calórica no último terço gestacional, sobre parâmetros biométricos, bioquímicos, molecular e funcional da prole recém desmamada e adulta, bem como, sobre parâmetros bioquímicos do leite materno. Ratas Wistar foram submetidas a restrição alimentar (50%) durante o último terço gestacional (grupo RA50), enquanto as ratas controles receberam alimentação ad libitum durante toda a gestação (grupo CONT). Ao nascimento, quantificou-se o número de nativivos, peso, tamanho e o sexo dos filhotes, bem como ajustou-se o tamanho da ninhada para 8 filhotes/mãe. Aos 6º, 11º e 16º dia de lactação, quantificou-se a ingestão de leite. Ao 12º dia de aleitamento, retirou-se amostra de leite para avaliação do crematócrito e parâmetros bioquímicos e ao 22º dia realizou-se o desmame, onde metade dos animais foi eutanasiada para remoção tecidual (tecido adiposo branco e marrom e hipotálamo) para análises biométrica e molecular, e também coleta sanguínea para análises bioquímicas (glicemia, perfil lipídico e hormonal). As matrizes também foram eutanasiadas para coletado sanguínea e posterior análise bioquímica. A outra metade foi mantida até a idade adulta. O peso corporal e ingestão alimentar foram avaliados a cada dois dias. Aos 90 dias de vida, avaliou-se a ingestão alimentar individual no ciclo escuro. Aos 100 dias de vida, os ratos foram eutanasiados para a coleta de sangue, estoques de gordura e tecido muscular esquelético para análises bioquímicas e biométricas, e a aorta torácica removida e isolada para avaliar a reatividade vascular. Em relação as ratas CONT, o leite das ratas RA50 mostrou-se mais energético (22%; P<0,05), rico em glicose (27%; P<0,01), colesterol total (41%; P<0,05), triglicérides (2%; P<0,05), bem como com alteração nos valores de hormônios metabólicos, rico em grelina acilada (70%; P<0,05) e pobre em leptina (78%; P<0,001) e corticosterona (14%; P<0,05). Em comparação às ratas CONT, as ratas RA50 apresentaram hipoglicemia (23%, P<0,001) e aumento nos valores de triglicéride (38%; P<0,01) e colesterol VLDL (38%; P<0,01) e leptina (155%; P<0,001) sem alteração nos níveis de grelina acilada e corticosterona. Os ratos RA50 em comparação aos CONT nasceram com peso e comprimento naso-anal menores (P<0,001). Durante a lactação a evolução do peso corporal e ingestão de leite do grupo RA50 foram maiores em relação ao grupo CONT (P<0,001). Ao desmame os ratos RA50 apresentaram fenótipo obeso (P<0,001), hiperglicemia, resistência à insulina e dislipidemia (P<0,05), hipergrelinemia (64%; P<0,05) e hiperleptinemia (82%; P<0,01), assim como maior expressão hipotalâmica do receptor de grelina (~4 vezes maior, P<0,01) quando comparados aos CONT. Quanto aos dados da prole adulta, os ratos RA50 apresentaram fenótipo obeso (P<0,05), hiperglicemia (12%; P<0,001), hipertrigliceridemia (16%; P<0,01), resistênciaà insulina (+3%; P<0,001), dislipidemia (P<0,05) e índices Castelli I (+46%; P<0,01) e II (+59%; P<0,01) elevados; bem como disfunção na resposta contrátil vascular na aorta torácica (P<0,01). Concluímos que a desnutrição no último terço gestacional, promove alterações na composição bioquímica, energética e no padrão de hormônios metabólicos do leite materno, possivelmente contribuindo para a programação do fenótipo obeso da prole já na infância, o que sugere uma relação com a hiperfagia e maior quantidade hipotalâmica de receptor de grelina nessa fase de desenvolvimento. Em adição, conclui-se, que o fenótipo obeso e dislipidêmico se estende ao longo da vida, bem como há nos ratos RA50 uma maior propensão ao desenvolvimento de doenças cardiovasculares.Universidade Federal de Mato GrossoBrasilInstituto de Ciências da Saúde (ICS) - SinopUFMT CUS - SinopPrograma de Pós-Graduação em Ciências em SaúdeOliveira, Júlio Cezar dehttp://lattes.cnpq.br/0189760778239540Miranda, Rosiane Aparecida083.736.496-54http://lattes.cnpq.br/3017049235974350Bomfim, Gisele Facholi693.500.941-34http://lattes.cnpq.br/5548680615131667039.925.254-14Oliveira, Júlio Cezar de039.925.254-14http://lattes.cnpq.br/0189760778239540Parrela, Jocemara Patricia Silva de Souza2024-08-21T17:20:47Z2022-02-022024-08-21T17:20:47Z2021-10-27info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisPARRELA, Jocemara Patricia Silva de Souza. Restrição calórica materna no último terço gestacional e as consequências de curto e longo prazo sobre o metabolismo da prole. 2021. 95 f. Dissertação (Mestrado em Ciências em Saúde) - Universidade Federal de Mato Grosso, Campus Universitário de Sinop, Instituto de Ciências da Saúde, Sinop, 2021.http://ri.ufmt.br/handle/1/5771porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMTinstname:Universidade Federal de Mato Grosso (UFMT)instacron:UFMT2024-08-24T07:01:36Zoai:localhost:1/5771Repositório InstitucionalPUBhttp://ri.ufmt.br/oai/requestjordanbiblio@gmail.comopendoar:2024-08-24T07:01:36Repositório Institucional da UFMT - Universidade Federal de Mato Grosso (UFMT)false
dc.title.none.fl_str_mv Restrição calórica materna no último terço gestacional e as consequências de curto e longo prazo sobre o metabolismo da prole
title Restrição calórica materna no último terço gestacional e as consequências de curto e longo prazo sobre o metabolismo da prole
spellingShingle Restrição calórica materna no último terço gestacional e as consequências de curto e longo prazo sobre o metabolismo da prole
Parrela, Jocemara Patricia Silva de Souza
Programação cardiometabólica
Desnutrição intrauterina
Leptina
Grelina
Obesidade
CNPQ::CIENCIAS DA SAUDE::MEDICINA
Cardiometabolic programming
Intrauterine malnutrition
Leptin
Ghrelin
Obesity
title_short Restrição calórica materna no último terço gestacional e as consequências de curto e longo prazo sobre o metabolismo da prole
title_full Restrição calórica materna no último terço gestacional e as consequências de curto e longo prazo sobre o metabolismo da prole
title_fullStr Restrição calórica materna no último terço gestacional e as consequências de curto e longo prazo sobre o metabolismo da prole
title_full_unstemmed Restrição calórica materna no último terço gestacional e as consequências de curto e longo prazo sobre o metabolismo da prole
title_sort Restrição calórica materna no último terço gestacional e as consequências de curto e longo prazo sobre o metabolismo da prole
author Parrela, Jocemara Patricia Silva de Souza
author_facet Parrela, Jocemara Patricia Silva de Souza
author_role author
dc.contributor.none.fl_str_mv Oliveira, Júlio Cezar de
http://lattes.cnpq.br/0189760778239540
Miranda, Rosiane Aparecida
083.736.496-54
http://lattes.cnpq.br/3017049235974350
Bomfim, Gisele Facholi
693.500.941-34
http://lattes.cnpq.br/5548680615131667
039.925.254-14
Oliveira, Júlio Cezar de
039.925.254-14
http://lattes.cnpq.br/0189760778239540
dc.contributor.author.fl_str_mv Parrela, Jocemara Patricia Silva de Souza
dc.subject.por.fl_str_mv Programação cardiometabólica
Desnutrição intrauterina
Leptina
Grelina
Obesidade
CNPQ::CIENCIAS DA SAUDE::MEDICINA
Cardiometabolic programming
Intrauterine malnutrition
Leptin
Ghrelin
Obesity
topic Programação cardiometabólica
Desnutrição intrauterina
Leptina
Grelina
Obesidade
CNPQ::CIENCIAS DA SAUDE::MEDICINA
Cardiometabolic programming
Intrauterine malnutrition
Leptin
Ghrelin
Obesity
description Intrauterine malnutrition at critical stages of development increases the vulnerability to metabolic diseases in adult life. The present study aimed to evaluate the effects of calorie restriction in the last third of gestation, on biometric, biochemical, molecular and functional parameters of just weaned and adult rat offspring, as well as on biochemical parameters of breast milk. Female Wistar rats were submitted to food restriction (50%) during the last third of gestation (FR50 group), while control rats were fed ad libitum throughout pregnancy (CONT group). At birth, the birthweight, number of livebirths, naso-anus length and sex of pups were assessed, as well as the litter size adjusted to 8 pups/mother. On the 6th, 11th and 16th day of lactation, milk intake was quantified. On the 12th day of lactation, a milk sample was taken to evaluate the energy content, biochemical parameters. On the 22nd day of age, weaning was performed, where a half of rat offspring was euthanized for tissue removal (white and brown adipose tissue and hypothalamus) for biometric and molecular analysis, and blood collected for biochemical analysis (glycemia, lipid and metabolic hormonal profile). In addition, mothers were euthanized for blood collection and subsequent biochemical analysis. The other half of rat offspring was kept into adulthood. Body weight and food intake were measured every two days. At 90 days of age, individual food intake in the dark cycle was evaluated. At 100 days of age, rat offspring were euthanized to collect blood, fat stores and skeletal muscle for biochemical and biometric analysis, and thoracic aorta removed and isolated to assess vascular reactivity. In relation to CONT mothers, milk from FR50 mothers display higher energy content (22%; P<0.05). It was richer in glucose (27%; P<0.01), total cholesterol (41%; P<0.05), triglycerides (2%; P<0.05), as well as with changes in the metabolic hormone values, rich in acylated ghrelin (70%; P<0.05) and poor in leptin (78%; P<0.001) and corticosterone (14%; P<0.05). Compared to CONT mothers, FR50 rats presented hypoglycemia (23%, P<0.001) and increased values of triglyceride (38%; P<0.01) and VLDL cholesterol (38%; P<0.01) and leptin (155%; P<0.001) without changes in acylated ghrelin and corticosterone levels. The FR50 rat offspring, compared to CONT rats, were born with small naso-anus length and body weight (P<0.001). During lactation, the evolution of body weight and milk intake in the FR50 group were higher compared to the CONT group (P<0.001). At weaning, FR50 rat offspring presented obese phenotype (P<0.001), hyperglycemia, insulin resistance and dyslipidemia (P<0.05), hyperghrelinemia (64%; P<0.05) and hyperleptinemia (82%; P<0.01), as well as up regulation of hypothalamic ghrelin receptor (~4-fold, P<0.01), when compared to CONT. Regarding data in adulthood, FR50 rats presented obese phenotype (P<0.05), hyperglycemia (12%; P<0.001), hypertriglyceridemia (16%; P<0.01), insulin resistance (+3%; P<0.001), dyslipidemia (P<0.05) and high Castelli I (+46%; P<0.01) and II (+59%; P<0.01) indices; as well as dysfunction in the vascular contractile response in the thoracic aorta (P<0.01). We conclude that malnutrition in the last third of gestation promotes changes in the biochemical, energetic and in the metabolic hormones composition in breast milk, possibly contributing to the programming of obese phenotype of rat offspring in childhood, which suggest a relation with hyperphagia and greater amount of ghrelin receptor in hypothalamus at this stage of development. In addition, it is summarized that the obese and dyslipidemic phenotype extend throughout life, and that FR50 rats are more likely to develop cardiovascular diseases.
publishDate 2021
dc.date.none.fl_str_mv 2021-10-27
2022-02-02
2024-08-21T17:20:47Z
2024-08-21T17:20:47Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv PARRELA, Jocemara Patricia Silva de Souza. Restrição calórica materna no último terço gestacional e as consequências de curto e longo prazo sobre o metabolismo da prole. 2021. 95 f. Dissertação (Mestrado em Ciências em Saúde) - Universidade Federal de Mato Grosso, Campus Universitário de Sinop, Instituto de Ciências da Saúde, Sinop, 2021.
http://ri.ufmt.br/handle/1/5771
identifier_str_mv PARRELA, Jocemara Patricia Silva de Souza. Restrição calórica materna no último terço gestacional e as consequências de curto e longo prazo sobre o metabolismo da prole. 2021. 95 f. Dissertação (Mestrado em Ciências em Saúde) - Universidade Federal de Mato Grosso, Campus Universitário de Sinop, Instituto de Ciências da Saúde, Sinop, 2021.
url http://ri.ufmt.br/handle/1/5771
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Universidade Federal de Mato Grosso
Brasil
Instituto de Ciências da Saúde (ICS) - Sinop
UFMT CUS - Sinop
Programa de Pós-Graduação em Ciências em Saúde
publisher.none.fl_str_mv Universidade Federal de Mato Grosso
Brasil
Instituto de Ciências da Saúde (ICS) - Sinop
UFMT CUS - Sinop
Programa de Pós-Graduação em Ciências em Saúde
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFMT
instname:Universidade Federal de Mato Grosso (UFMT)
instacron:UFMT
instname_str Universidade Federal de Mato Grosso (UFMT)
instacron_str UFMT
institution UFMT
reponame_str Repositório Institucional da UFMT
collection Repositório Institucional da UFMT
repository.name.fl_str_mv Repositório Institucional da UFMT - Universidade Federal de Mato Grosso (UFMT)
repository.mail.fl_str_mv jordanbiblio@gmail.com
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