Efeitos metabólicos, comportamentais e cardiovasculares da restrição alimentar durante a puberdade em ratos adultos obesos e não obesos

Detalhes bibliográficos
Autor(a) principal: Cavalet, Letícia Chavaglia
Data de Publicação: 2019
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFG
Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/9520
Resumo: Environmental and nutritional disorders during the perinatal period cause metabolic dysfunction in the progeny and impairs health through epigenetic programming, which is observable in the small litter (SL) experimental model. Therefore, severe caloric restriction has the potential of affecting several organic systems through the same epigenetic mechanisms, and its effects need elucidation. The objective of this work was to determine whether the food restriction would impact behavioral and cardiovascular parameters in obese and non-obese animals, and the implications to the renin-angiotensin system (RAS) as well as MAPK/ERK in these animals’ hearts. Three days after delivery, female Wistar rats were separated in small litter (SL, 3 pups) and normal litter (NL, 9 pups) groups, their offspring in turn were subjected to food restriction (50%), while another group had free access to chow during the puberty period (from 30 to 60 days). These animals were then subjected to non-anaesthetized recording for the evaluation of cardiovascular parameters, open field (OF), elevated plus maze (EPM) and forced swimming (FS) tests for behavioural analysis. In addition, their body weight and food intake were monitored throughout the experimental period. Finally, the animals were anesthetized, euthanized and had their organs harvested, weighted and preserved for subsequent histological and western blot analysis. SL and SLR offspring were overweight (p<0.05), developing the obese phenotype, observable through increased deposits of white adipose tissue (p<0.05). Differences in mean arterial pressure were also observed, when comparing small litter control animals with the rest of the groups (p<0.05). In addition, SL and SLR offspring showed a tendency for anxiety-like behaviour during the OF test, considering immobility time (p<0.05), and EPM tests considering the number of entries into the open arms (p<0.05). Cardiac remodelling in the NLR and SLR groups was also observed, through the presence of interstitial and perivascular fibrosis (p<0.05), as well as higher expressions of the receptors AT1 and AT2, and of the proteins ERK and p-ERK (p<0.05). The present study shows that early overnutrition caused obesity, anxiety-like behaviours and increases to blood pressure. Also, the animals which underwent food restriction showed no improvement in the behavioural tests, however the non-obese animals subjected to the diet showed similar impairments in behaviour, and for the first time it was shown that severe food restriction caused cardiac remodelling, suggesting that severe food restriction during puberty is capable of causing metabolic programming, negatively impacting these animals later in adult life.
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spelling Gomes, Rodrigo Mellohttp://lattes.cnpq.br/3121095341590269Pedrino, Gustavo Rodrigueshttp://lattes.cnpq.br/1155446449250341Gomes, Rodrigo MelloCustódio, Carlos Henrique XavierCorgosinho, Flávia Camposhttp://lattes.cnpq.br/2767590817270632Cavalet, Letícia Chavaglia2019-04-23T11:41:07Z2019-04-02CAVALET, L. C. Efeitos metabólicos, comportamentais e cardiovasculares da restrição alimentar durante a puberdade em ratos adultos obesos e não obesos. 2019. 60 f. Dissertação (Mestrado em Ciências Biológicas) - Universidade Federal de Goiás, Goiânia, 2019.http://repositorio.bc.ufg.br/tede/handle/tede/9520Environmental and nutritional disorders during the perinatal period cause metabolic dysfunction in the progeny and impairs health through epigenetic programming, which is observable in the small litter (SL) experimental model. Therefore, severe caloric restriction has the potential of affecting several organic systems through the same epigenetic mechanisms, and its effects need elucidation. The objective of this work was to determine whether the food restriction would impact behavioral and cardiovascular parameters in obese and non-obese animals, and the implications to the renin-angiotensin system (RAS) as well as MAPK/ERK in these animals’ hearts. Three days after delivery, female Wistar rats were separated in small litter (SL, 3 pups) and normal litter (NL, 9 pups) groups, their offspring in turn were subjected to food restriction (50%), while another group had free access to chow during the puberty period (from 30 to 60 days). These animals were then subjected to non-anaesthetized recording for the evaluation of cardiovascular parameters, open field (OF), elevated plus maze (EPM) and forced swimming (FS) tests for behavioural analysis. In addition, their body weight and food intake were monitored throughout the experimental period. Finally, the animals were anesthetized, euthanized and had their organs harvested, weighted and preserved for subsequent histological and western blot analysis. SL and SLR offspring were overweight (p<0.05), developing the obese phenotype, observable through increased deposits of white adipose tissue (p<0.05). Differences in mean arterial pressure were also observed, when comparing small litter control animals with the rest of the groups (p<0.05). In addition, SL and SLR offspring showed a tendency for anxiety-like behaviour during the OF test, considering immobility time (p<0.05), and EPM tests considering the number of entries into the open arms (p<0.05). Cardiac remodelling in the NLR and SLR groups was also observed, through the presence of interstitial and perivascular fibrosis (p<0.05), as well as higher expressions of the receptors AT1 and AT2, and of the proteins ERK and p-ERK (p<0.05). The present study shows that early overnutrition caused obesity, anxiety-like behaviours and increases to blood pressure. Also, the animals which underwent food restriction showed no improvement in the behavioural tests, however the non-obese animals subjected to the diet showed similar impairments in behaviour, and for the first time it was shown that severe food restriction caused cardiac remodelling, suggesting that severe food restriction during puberty is capable of causing metabolic programming, negatively impacting these animals later in adult life.Perturbações ambientais e nutricionais durante o período perinatal causam disfunções metabólicas na prole através de alterações epigenéticas afetando negativamente a saúde em geral. Portanto, a restrição alimentar possui o potencial de afetar o organismo através dos mesmos mecanismos, e seus efeitos em animais metabolicamente programados para obesidade precisam ser elucidados. O objetivo deste trabalho foi determinar se a restrição alimentar impactaria parâmetros comportamentais e cardiovasculares de animais obesos e não obesos e o envolvimento do sistema renina angiotensina (SRA) e da MAPK / ERK no coração desses animais. Três dias após o nascimento, ratas Wistar foram separadas em grupos small litter (SL, 3 filhotes) ou normal litter (NL, 9 filhotes). Posteriormente uma leva de animais de ambas as proles foram submetidos a restrição alimentar (50%) enquanto outra leva permaneceu com livre acesso a alimento durante o período da puberdade (dos 30 aos 60 dias). Aos 120 dias, foi realizado registro acordado para a avaliação de parâmetros cardiovasculares, testes de campo aberto (CA), labirinto em cruz elevado (LCE) e nado forçado (NF) para avaliação de parâmetros comportamentais. Adicionalmente, o peso corporal e ingestão alimentar foram monitorados durante todo o período experimental. Por fim, os animais foram anestesiados e eutanasiados para coleta de tecidos, para a subsequente realização de western blot e histologia. Os animais SL e SLR apresentaram sobrepeso, desenvolvendo o fenótipo de obesidade, visível através de depósitos de gorduras aumentados (p<0.05). Diferenças na pressão arterial sistólica e diastólica também foram observadas, quando comparando animais SL com os demais grupos (p<0.05). Adicionalmente, as proles SL e SLR demonstraram uma tendência a comportamento tipo-ansiedade durante os testes comportamentais, considerando o tempo de imobilidade durante o teste CA (p<0.05), e o número de entradas nos braços abertos durante o LCE (p<0.05). Também foi constatada a presença de remodelamento cardíaco nos animais NLR e SLR, a partir da presença de fibrose perivascular e intersticial (p<0.05), assim como alterações na expressão dos receptores AT1, AT2 e das proteínas ERK e p-ERK (p<0.05). O presente estudo demonstrou que supernutrição precoce causou obesidade, comportamento tipo-ansiedade e aumento da pressão sanguínea. Adicionalmente, os animais submetidos a restrição alimentar não demonstraram melhoras nos testes comportamentais, contudo os animais não obesos submetidos a dieta demonstraram similarmente comportamento tipo-ansiedade, e pela primeira vez foi demonstrado que restrição alimentar tem a capacidade de causar remodelamento cardíaco, sugerindo que a restrição alimentar severa durante a adolescência é capaz de desencadear programação metabólica, afetando negativamente estes animais durante a vida adulta.Submitted by Ana Caroline Costa (ana_caroline212@hotmail.com) on 2019-04-22T19:09:43Z No. of bitstreams: 2 Dissertação - Letícia Chavaglia Cavalet - 2019.pdf: 3951447 bytes, checksum: 66a5fbacedbd61249232c6ff07d5620c (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2019-04-23T11:41:07Z (GMT) No. of bitstreams: 2 Dissertação - Letícia Chavaglia Cavalet - 2019.pdf: 3951447 bytes, checksum: 66a5fbacedbd61249232c6ff07d5620c (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Made available in DSpace on 2019-04-23T11:41:07Z (GMT). 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dc.title.eng.fl_str_mv Efeitos metabólicos, comportamentais e cardiovasculares da restrição alimentar durante a puberdade em ratos adultos obesos e não obesos
dc.title.alternative.eng.fl_str_mv Metabolic, behavioral and cardiovascular effects of food restriction during puberty in adult obese and non obese rats
title Efeitos metabólicos, comportamentais e cardiovasculares da restrição alimentar durante a puberdade em ratos adultos obesos e não obesos
spellingShingle Efeitos metabólicos, comportamentais e cardiovasculares da restrição alimentar durante a puberdade em ratos adultos obesos e não obesos
Cavalet, Letícia Chavaglia
Programação cardiometabólica
Redução de ninhada
Restrição alimentar
Obesidade
Cardiovascular
Comportamento
Cardiometabolic programming
Litter size reduction
Food restriction
Obesity
Behavior
CIENCIAS BIOLOGICAS
title_short Efeitos metabólicos, comportamentais e cardiovasculares da restrição alimentar durante a puberdade em ratos adultos obesos e não obesos
title_full Efeitos metabólicos, comportamentais e cardiovasculares da restrição alimentar durante a puberdade em ratos adultos obesos e não obesos
title_fullStr Efeitos metabólicos, comportamentais e cardiovasculares da restrição alimentar durante a puberdade em ratos adultos obesos e não obesos
title_full_unstemmed Efeitos metabólicos, comportamentais e cardiovasculares da restrição alimentar durante a puberdade em ratos adultos obesos e não obesos
title_sort Efeitos metabólicos, comportamentais e cardiovasculares da restrição alimentar durante a puberdade em ratos adultos obesos e não obesos
author Cavalet, Letícia Chavaglia
author_facet Cavalet, Letícia Chavaglia
author_role author
dc.contributor.advisor1.fl_str_mv Gomes, Rodrigo Mello
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/3121095341590269
dc.contributor.advisor-co1.fl_str_mv Pedrino, Gustavo Rodrigues
dc.contributor.advisor-co1Lattes.fl_str_mv http://lattes.cnpq.br/1155446449250341
dc.contributor.referee1.fl_str_mv Gomes, Rodrigo Mello
dc.contributor.referee2.fl_str_mv Custódio, Carlos Henrique Xavier
dc.contributor.referee3.fl_str_mv Corgosinho, Flávia Campos
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/2767590817270632
dc.contributor.author.fl_str_mv Cavalet, Letícia Chavaglia
contributor_str_mv Gomes, Rodrigo Mello
Pedrino, Gustavo Rodrigues
Gomes, Rodrigo Mello
Custódio, Carlos Henrique Xavier
Corgosinho, Flávia Campos
dc.subject.por.fl_str_mv Programação cardiometabólica
Redução de ninhada
Restrição alimentar
Obesidade
Cardiovascular
Comportamento
topic Programação cardiometabólica
Redução de ninhada
Restrição alimentar
Obesidade
Cardiovascular
Comportamento
Cardiometabolic programming
Litter size reduction
Food restriction
Obesity
Behavior
CIENCIAS BIOLOGICAS
dc.subject.eng.fl_str_mv Cardiometabolic programming
Litter size reduction
Food restriction
Obesity
Behavior
dc.subject.cnpq.fl_str_mv CIENCIAS BIOLOGICAS
description Environmental and nutritional disorders during the perinatal period cause metabolic dysfunction in the progeny and impairs health through epigenetic programming, which is observable in the small litter (SL) experimental model. Therefore, severe caloric restriction has the potential of affecting several organic systems through the same epigenetic mechanisms, and its effects need elucidation. The objective of this work was to determine whether the food restriction would impact behavioral and cardiovascular parameters in obese and non-obese animals, and the implications to the renin-angiotensin system (RAS) as well as MAPK/ERK in these animals’ hearts. Three days after delivery, female Wistar rats were separated in small litter (SL, 3 pups) and normal litter (NL, 9 pups) groups, their offspring in turn were subjected to food restriction (50%), while another group had free access to chow during the puberty period (from 30 to 60 days). These animals were then subjected to non-anaesthetized recording for the evaluation of cardiovascular parameters, open field (OF), elevated plus maze (EPM) and forced swimming (FS) tests for behavioural analysis. In addition, their body weight and food intake were monitored throughout the experimental period. Finally, the animals were anesthetized, euthanized and had their organs harvested, weighted and preserved for subsequent histological and western blot analysis. SL and SLR offspring were overweight (p<0.05), developing the obese phenotype, observable through increased deposits of white adipose tissue (p<0.05). Differences in mean arterial pressure were also observed, when comparing small litter control animals with the rest of the groups (p<0.05). In addition, SL and SLR offspring showed a tendency for anxiety-like behaviour during the OF test, considering immobility time (p<0.05), and EPM tests considering the number of entries into the open arms (p<0.05). Cardiac remodelling in the NLR and SLR groups was also observed, through the presence of interstitial and perivascular fibrosis (p<0.05), as well as higher expressions of the receptors AT1 and AT2, and of the proteins ERK and p-ERK (p<0.05). The present study shows that early overnutrition caused obesity, anxiety-like behaviours and increases to blood pressure. Also, the animals which underwent food restriction showed no improvement in the behavioural tests, however the non-obese animals subjected to the diet showed similar impairments in behaviour, and for the first time it was shown that severe food restriction caused cardiac remodelling, suggesting that severe food restriction during puberty is capable of causing metabolic programming, negatively impacting these animals later in adult life.
publishDate 2019
dc.date.accessioned.fl_str_mv 2019-04-23T11:41:07Z
dc.date.issued.fl_str_mv 2019-04-02
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.citation.fl_str_mv CAVALET, L. C. Efeitos metabólicos, comportamentais e cardiovasculares da restrição alimentar durante a puberdade em ratos adultos obesos e não obesos. 2019. 60 f. Dissertação (Mestrado em Ciências Biológicas) - Universidade Federal de Goiás, Goiânia, 2019.
dc.identifier.uri.fl_str_mv http://repositorio.bc.ufg.br/tede/handle/tede/9520
identifier_str_mv CAVALET, L. C. Efeitos metabólicos, comportamentais e cardiovasculares da restrição alimentar durante a puberdade em ratos adultos obesos e não obesos. 2019. 60 f. Dissertação (Mestrado em Ciências Biológicas) - Universidade Federal de Goiás, Goiânia, 2019.
url http://repositorio.bc.ufg.br/tede/handle/tede/9520
dc.language.iso.fl_str_mv por
language por
dc.relation.program.fl_str_mv -3362730732320261554
dc.relation.confidence.fl_str_mv 600
600
600
600
dc.relation.department.fl_str_mv -3872772117827373404
dc.relation.cnpq.fl_str_mv -3439178843068202161
dc.relation.sponsorship.fl_str_mv -2555911436985713659
dc.rights.driver.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Goiás
dc.publisher.program.fl_str_mv Programa de Pós-graduação em Ciências Biológicas (ICB)
dc.publisher.initials.fl_str_mv UFG
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Instituto de Ciências Biológicas - ICB (RG)
publisher.none.fl_str_mv Universidade Federal de Goiás
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFG
instname:Universidade Federal de Goiás (UFG)
instacron:UFG
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