Effects of the combination of intermittent fasting and physical exercise on autophagic and leptin pathway in the hypothalamus of obese mice

Detalhes bibliográficos
Autor(a) principal: Oliveira, Luciana da Costa
Data de Publicação: 2022
Tipo de documento: Tese
Idioma: eng
Título da fonte: Biblioteca Digital de Teses e Dissertações da USP
Texto Completo: https://www.teses.usp.br/teses/disponiveis/17/17164/tde-06022023-105659/
Resumo: Diet-induced obesity is associated with persistent low-grade inflammation in the hypothalamus which promotes the development of central leptin resistance. This inflammatory process involves dysregulation of the hypothalamic autophagic pathway, compromising the dynamics of activation/inhibition of the orexigenic AgRP neurons (associated with the sensation of hunger) and the anorectic POMC (associated with the sensation of satiety), deregulating energy homeostasis and predisposing to weight gain. Studies point out that fasting (IF) and physical exercise (E) are capable of modulating hypothalamic inflammatory proteins and activate/inhibit neuropeptides; in this sense, we hypothesized that there is possible that the combination of the protocols (IF and execise) would bring more expressive effects in the reestablishment of hypothalamic sensitivity to leptin. Objective: to investigate the effect of the association of IF with combined E on inflammatory, autophagy and leptin pathways in the hypothalamus of high-fat diet fed mice. Methodology: mice were divided into 5 groups: two controls: standard diet (C) and high fat diet (HF); and 3 intervention groups: high fat diet-trained (HF-T), high fat diet-intermittent fasting (HF-IF), and high fat diet-intermittent fasting and trained (HF-IFT). The methods used were: immunohistochemistry, Immunoblotting, RT-PCR, ELISA and ITT, in addition to the analysis of body mass and food intake. Mains Results: compared to the HF group, only the groups that performed the IF showed a reduction in the evaluated hypothalamic inflammatory proteins and an increase in POMC mRNA expression. After intraperitoneal stimulation with leptin, the HF-IFT group showed an increase in pSTAT3 in ARQ and VMH compared to the HF, HF-T and HF-IF groups. The three interventions showed lower caloric intake and body mass compared to the HF group, suggesting a correction in hyperphagic behavior and resistance to diet-induced weight gain. Conclusion: these data indicate that the beneficial effects of the combination of IF and physical exercise on energy homeostasis may be associated with improved leptin sensitivity in ARC and VMH, probably due, at least in part, to the reduction of hypothalamic SOCS3 and improved autophagic response.
id USP_0f19f84653a443d89801f26a8238e10e
oai_identifier_str oai:teses.usp.br:tde-06022023-105659
network_acronym_str USP
network_name_str Biblioteca Digital de Teses e Dissertações da USP
repository_id_str 2721
spelling Effects of the combination of intermittent fasting and physical exercise on autophagic and leptin pathway in the hypothalamus of obese miceEfeitos da combinação do jejum intermitente com o exercício físico sobre a via autofágica e via da leptina no hipotálamo de camundongos obesosExercício físicoHipotálamoHypothalamusIntermittent fastingJejum intermitenteObesidadeObesityPhysical exerciseDiet-induced obesity is associated with persistent low-grade inflammation in the hypothalamus which promotes the development of central leptin resistance. This inflammatory process involves dysregulation of the hypothalamic autophagic pathway, compromising the dynamics of activation/inhibition of the orexigenic AgRP neurons (associated with the sensation of hunger) and the anorectic POMC (associated with the sensation of satiety), deregulating energy homeostasis and predisposing to weight gain. Studies point out that fasting (IF) and physical exercise (E) are capable of modulating hypothalamic inflammatory proteins and activate/inhibit neuropeptides; in this sense, we hypothesized that there is possible that the combination of the protocols (IF and execise) would bring more expressive effects in the reestablishment of hypothalamic sensitivity to leptin. Objective: to investigate the effect of the association of IF with combined E on inflammatory, autophagy and leptin pathways in the hypothalamus of high-fat diet fed mice. Methodology: mice were divided into 5 groups: two controls: standard diet (C) and high fat diet (HF); and 3 intervention groups: high fat diet-trained (HF-T), high fat diet-intermittent fasting (HF-IF), and high fat diet-intermittent fasting and trained (HF-IFT). The methods used were: immunohistochemistry, Immunoblotting, RT-PCR, ELISA and ITT, in addition to the analysis of body mass and food intake. Mains Results: compared to the HF group, only the groups that performed the IF showed a reduction in the evaluated hypothalamic inflammatory proteins and an increase in POMC mRNA expression. After intraperitoneal stimulation with leptin, the HF-IFT group showed an increase in pSTAT3 in ARQ and VMH compared to the HF, HF-T and HF-IF groups. The three interventions showed lower caloric intake and body mass compared to the HF group, suggesting a correction in hyperphagic behavior and resistance to diet-induced weight gain. Conclusion: these data indicate that the beneficial effects of the combination of IF and physical exercise on energy homeostasis may be associated with improved leptin sensitivity in ARC and VMH, probably due, at least in part, to the reduction of hypothalamic SOCS3 and improved autophagic response.A obesidade induzida pela dieta é associada a inflamação de baixo grau persistente no hipotálamo a qual promove o desenvolvimento da resistência central a leptina. Esse processo inflamatório envolve a desregulação da via autofágica hipotalâmica comprometendo a dinâmica da ativação/inibição dos neurônios orexígenos AgRP (associados a sensação de fome) e anorexígenos POMC (associados a sensação de saciedade), desregulando a homesostase energética e predispondo ao ganho de peso. Estudos apontam que tanto o jejum intermitente (JI) quanto o exercício físico (EF) são capazes de modular proteínas inflamatórias hipotalâmicas e atuar na ativação/inibição de neuropeptídios; nesse sentido, é possível hipotetizar que a combinação dos protocolos (JI e EF) traria efeitos mais expressivos no reestabelecimento da sensibilidade hipotalâmica a leptina. Objetivo: investigar o efeito da associação do JI com o EF combinado nas vias inflamatória, da autofagia e da leptina no hipotálamo de camundongos alimentados com dieta hiperlipídica. Metodologia: os camundongos foram divididos em 5 grupos: sendo dois controles: dieta padrão (DP) e dieta hiperlipídica (DH); e 3 grupos de intervenção: dieta hiperlipídica-treinados (DH-T), dieta hiperlipídica-jejum intermitente (DH-JI), e dieta hiperlipídica-jejum intermitente e treinados (DH-JIT). Os métodos utilizados foram: imuno-histoquímica, Immunoblotting, RTqPCR, ELISA e ITT, além das análises da massa corporal e ingestão alimentar. Principais resultados: comparado ao grupo DH, apenas os grupos que realizaram o JI apresentaram redução nas proteínas inflamatórias hipotalâmicas avaliadas e aumento na expressão de RNAm de POMC. Após estimulação intraperitoneal com leptina o grupo DH-JIT apresentou aumento da pSTAT3 no ARQ e VMH em comparação com os grupos DH, DH-T e DH-JI. As três intervenções apresentaram menor ingestão calórica e massa corporal quando comparadas ao grupo DH, sugerindo melhora no comportamento hiperfágico e resistência ao ganho de peso induzido pela dieta. Conclusão: nossos dados indicam que os efeitos benéficos da combinação do JI e EF na homeostase energética pode estar associada a melhora da sensibilidade à leptina no ARC e VMH, provavelmente se deve parcialmente à redução da SOCS3 hipotalâmica e melhora na resposta autofágica.Biblioteca Digitais de Teses e Dissertações da USPSilva, Adelino Sanchez Ramos daOliveira, Luciana da Costa2022-11-21info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttps://www.teses.usp.br/teses/disponiveis/17/17164/tde-06022023-105659/reponame:Biblioteca Digital de Teses e Dissertações da USPinstname:Universidade de São Paulo (USP)instacron:USPLiberar o conteúdo para acesso público.info:eu-repo/semantics/openAccesseng2023-02-08T14:07:12Zoai:teses.usp.br:tde-06022023-105659Biblioteca Digital de Teses e Dissertaçõeshttp://www.teses.usp.br/PUBhttp://www.teses.usp.br/cgi-bin/mtd2br.plvirginia@if.usp.br|| atendimento@aguia.usp.br||virginia@if.usp.bropendoar:27212023-02-08T14:07:12Biblioteca Digital de Teses e Dissertações da USP - Universidade de São Paulo (USP)false
dc.title.none.fl_str_mv Effects of the combination of intermittent fasting and physical exercise on autophagic and leptin pathway in the hypothalamus of obese mice
Efeitos da combinação do jejum intermitente com o exercício físico sobre a via autofágica e via da leptina no hipotálamo de camundongos obesos
title Effects of the combination of intermittent fasting and physical exercise on autophagic and leptin pathway in the hypothalamus of obese mice
spellingShingle Effects of the combination of intermittent fasting and physical exercise on autophagic and leptin pathway in the hypothalamus of obese mice
Oliveira, Luciana da Costa
Exercício físico
Hipotálamo
Hypothalamus
Intermittent fasting
Jejum intermitente
Obesidade
Obesity
Physical exercise
title_short Effects of the combination of intermittent fasting and physical exercise on autophagic and leptin pathway in the hypothalamus of obese mice
title_full Effects of the combination of intermittent fasting and physical exercise on autophagic and leptin pathway in the hypothalamus of obese mice
title_fullStr Effects of the combination of intermittent fasting and physical exercise on autophagic and leptin pathway in the hypothalamus of obese mice
title_full_unstemmed Effects of the combination of intermittent fasting and physical exercise on autophagic and leptin pathway in the hypothalamus of obese mice
title_sort Effects of the combination of intermittent fasting and physical exercise on autophagic and leptin pathway in the hypothalamus of obese mice
author Oliveira, Luciana da Costa
author_facet Oliveira, Luciana da Costa
author_role author
dc.contributor.none.fl_str_mv Silva, Adelino Sanchez Ramos da
dc.contributor.author.fl_str_mv Oliveira, Luciana da Costa
dc.subject.por.fl_str_mv Exercício físico
Hipotálamo
Hypothalamus
Intermittent fasting
Jejum intermitente
Obesidade
Obesity
Physical exercise
topic Exercício físico
Hipotálamo
Hypothalamus
Intermittent fasting
Jejum intermitente
Obesidade
Obesity
Physical exercise
description Diet-induced obesity is associated with persistent low-grade inflammation in the hypothalamus which promotes the development of central leptin resistance. This inflammatory process involves dysregulation of the hypothalamic autophagic pathway, compromising the dynamics of activation/inhibition of the orexigenic AgRP neurons (associated with the sensation of hunger) and the anorectic POMC (associated with the sensation of satiety), deregulating energy homeostasis and predisposing to weight gain. Studies point out that fasting (IF) and physical exercise (E) are capable of modulating hypothalamic inflammatory proteins and activate/inhibit neuropeptides; in this sense, we hypothesized that there is possible that the combination of the protocols (IF and execise) would bring more expressive effects in the reestablishment of hypothalamic sensitivity to leptin. Objective: to investigate the effect of the association of IF with combined E on inflammatory, autophagy and leptin pathways in the hypothalamus of high-fat diet fed mice. Methodology: mice were divided into 5 groups: two controls: standard diet (C) and high fat diet (HF); and 3 intervention groups: high fat diet-trained (HF-T), high fat diet-intermittent fasting (HF-IF), and high fat diet-intermittent fasting and trained (HF-IFT). The methods used were: immunohistochemistry, Immunoblotting, RT-PCR, ELISA and ITT, in addition to the analysis of body mass and food intake. Mains Results: compared to the HF group, only the groups that performed the IF showed a reduction in the evaluated hypothalamic inflammatory proteins and an increase in POMC mRNA expression. After intraperitoneal stimulation with leptin, the HF-IFT group showed an increase in pSTAT3 in ARQ and VMH compared to the HF, HF-T and HF-IF groups. The three interventions showed lower caloric intake and body mass compared to the HF group, suggesting a correction in hyperphagic behavior and resistance to diet-induced weight gain. Conclusion: these data indicate that the beneficial effects of the combination of IF and physical exercise on energy homeostasis may be associated with improved leptin sensitivity in ARC and VMH, probably due, at least in part, to the reduction of hypothalamic SOCS3 and improved autophagic response.
publishDate 2022
dc.date.none.fl_str_mv 2022-11-21
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://www.teses.usp.br/teses/disponiveis/17/17164/tde-06022023-105659/
url https://www.teses.usp.br/teses/disponiveis/17/17164/tde-06022023-105659/
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv
dc.rights.driver.fl_str_mv Liberar o conteúdo para acesso público.
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Liberar o conteúdo para acesso público.
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.coverage.none.fl_str_mv
dc.publisher.none.fl_str_mv Biblioteca Digitais de Teses e Dissertações da USP
publisher.none.fl_str_mv Biblioteca Digitais de Teses e Dissertações da USP
dc.source.none.fl_str_mv
reponame:Biblioteca Digital de Teses e Dissertações da USP
instname:Universidade de São Paulo (USP)
instacron:USP
instname_str Universidade de São Paulo (USP)
instacron_str USP
institution USP
reponame_str Biblioteca Digital de Teses e Dissertações da USP
collection Biblioteca Digital de Teses e Dissertações da USP
repository.name.fl_str_mv Biblioteca Digital de Teses e Dissertações da USP - Universidade de São Paulo (USP)
repository.mail.fl_str_mv virginia@if.usp.br|| atendimento@aguia.usp.br||virginia@if.usp.br
_version_ 1815256759225286656