Effects of the combination of intermittent fasting and physical exercise on autophagic and leptin pathway in the hypothalamus of obese mice
Autor(a) principal: | |
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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. |
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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 |
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1815256759225286656 |