Effect of exercise training in skeletal muscle remodeling in heart failure with preserved ejection fraction
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Tipo de documento: | Dissertação |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10773/30039 |
Resumo: | Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome characterized by pulmonary congestion, dyspnea, elevated left ventricular filling pressures, normal left ventricular ejection fraction (LVEF ≥ 50%) and exercise intolerance. Although it is an increasingly common syndrome, its treatment remains quite limited, with available therapies focusing mostly on symptom relief. Intolerance to exercise training is one of the main symptoms presented by patients with HFpEF. Due to the known benefits of exercise training at cardiovascular levels, it has been recommended as adjuvant non-pharmacological therapy in the treatment of HFpEF. Indeed, the benefits of exercise training have already been documented in HFpEF, however the molecular mechanisms underlying those benefits remain poorly understood. Thus, this study aimed to study the molecular changes underlying exercise training effects in HFpEF. An animal model of HFpEF was used, namely obese ZSF1 rats. The animals were submitted to a treadmill exercise protocol for 4 weeks, after which exercise intolerance test and hemodynamic evaluation were performed. After animal sacrifice, the gastrocnemius muscle was collected for metabolic analysis by Nuclear Magnetic Resonance Spectroscopy and Western Blot protein expression evaluation. Comparison between the metabolic profiles of gastrocnemius of ZSF1 obese rats and ZSF1 lean (control) rats allowed to characterize the changes inherent to the disease. The results show that HFpEF promoted glycogen degradation in small oligosaccharides, resulting in the release of glucose-1-phosphate, as well as glucose-6-phosphate and glucose accumulation. In addition, decreased AMPK expression, impaired metabolism of ketone bodies and increased metabolism of amino acids such as glutamine and glutamate were also observed in the sedentary HFpEF group. The impact of exercise on gastrocnemius metabolism of this animal model was evaluated by comparing sedentary and exercised obese animals. The results obtained show that, as in sedentary animals, the exercised animals also showed a high rate of glycogen degradation, with no significant impact of exercise on glucose metabolism. Also, amino acid metabolism remained unchanged. However, the exercised group showed changes that suggest an increment in fatty acid betaoxidation and oxidative phosphorylation, as well as the reestablishment of ketone body metabolism. Overall, this work has shown that exercise has a positive impact on gastrocnemius metabolism thus supporting its supervised prescription to patients with HFpEF. |
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Effect of exercise training in skeletal muscle remodeling in heart failure with preserved ejection fractionHeart failure with preserved ejection fractionExercise trainingSkeletal muscleMetabolismHeart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome characterized by pulmonary congestion, dyspnea, elevated left ventricular filling pressures, normal left ventricular ejection fraction (LVEF ≥ 50%) and exercise intolerance. Although it is an increasingly common syndrome, its treatment remains quite limited, with available therapies focusing mostly on symptom relief. Intolerance to exercise training is one of the main symptoms presented by patients with HFpEF. Due to the known benefits of exercise training at cardiovascular levels, it has been recommended as adjuvant non-pharmacological therapy in the treatment of HFpEF. Indeed, the benefits of exercise training have already been documented in HFpEF, however the molecular mechanisms underlying those benefits remain poorly understood. Thus, this study aimed to study the molecular changes underlying exercise training effects in HFpEF. An animal model of HFpEF was used, namely obese ZSF1 rats. The animals were submitted to a treadmill exercise protocol for 4 weeks, after which exercise intolerance test and hemodynamic evaluation were performed. After animal sacrifice, the gastrocnemius muscle was collected for metabolic analysis by Nuclear Magnetic Resonance Spectroscopy and Western Blot protein expression evaluation. Comparison between the metabolic profiles of gastrocnemius of ZSF1 obese rats and ZSF1 lean (control) rats allowed to characterize the changes inherent to the disease. The results show that HFpEF promoted glycogen degradation in small oligosaccharides, resulting in the release of glucose-1-phosphate, as well as glucose-6-phosphate and glucose accumulation. In addition, decreased AMPK expression, impaired metabolism of ketone bodies and increased metabolism of amino acids such as glutamine and glutamate were also observed in the sedentary HFpEF group. The impact of exercise on gastrocnemius metabolism of this animal model was evaluated by comparing sedentary and exercised obese animals. The results obtained show that, as in sedentary animals, the exercised animals also showed a high rate of glycogen degradation, with no significant impact of exercise on glucose metabolism. Also, amino acid metabolism remained unchanged. However, the exercised group showed changes that suggest an increment in fatty acid betaoxidation and oxidative phosphorylation, as well as the reestablishment of ketone body metabolism. Overall, this work has shown that exercise has a positive impact on gastrocnemius metabolism thus supporting its supervised prescription to patients with HFpEF.A insuficiência cardíaca com fração de ejeção preservada (ICFEP) é uma síndrome clínica complexa caracterizada por congestão pulmonar, dispneia, pressões de enchimento do ventrículo esquerdo elevadas, fração de ejeção ventricular esquerda normal (FEVE ≥ 50%) e intolerância ao exercício físico. Embora seja uma síndrome cada vez mais comum, o seu tratamento continua bastante limitado, sendo que as terapias disponíveis se focam maioritariamente no alívio dos sintomas. A intolerância ao exercício fisíco é um dos principais sintomas apresentados pelos pacientes com ICFEP. Devido aos benefícios já conhecidos da prática de exercício físico para o sistema cardiovascular, este tem vindo a ser recomendado como terapia não farmacológica adjuvante no tratamento da ICFEP. Embora os benefícios do exercício fisíco tenham já sido documentados na ICFEP, os mecanismos moleculares subjacantes a esses benefícios permanecem pouco compreendidos. Este trabalho teve como objetivo global estudar as alterações moleculares subjacentes à prática de exercício fisíco na ICFEP. Foi utilizado um modelo animal de ICFEP, nomeadamente ratos ZSF1 obesos. Os animais foram submetidos a um protocolo de exercício em tapete rolante durante 4 semanas, ao fim das quais se procedeu ao teste de intolerância ao esforço e à avaliação hemodinâmica. Após o sacrifício dos animais, o músculo gastrocnemius foi colectado para realização de uma análise metabólomica por espetroscopia de Ressonância Magnética Nuclear e avaliação da expressão proteica por Western Blot. A comparação entre os perfis metabólicos do gastrocnemius de ratos ZSF1 obesos com o de ratos ZSF1 magros (controlo) permitiu caracterizar as alterações inerentes à doença. Os resultados mostram que a ICFEP promoveu a degradação do glicogénio em pequenos oligossacarídeos, de onde resultou a libertação de glucose-1-fosfato, havendo também acumulação de glucose-6- fosfato e glucose. Para além disso, destacam-se a diminuição da expressão da AMPK, o comprometimento do metabolismo de corpos cetónicos e um aumento da metabolização de aminoácidos como a glutamina e o glutamato. O impacto do exercício físico no metabolismo do gastrocnemius deste modelo animal foi avaliado através da comparação entre animais obesos sedentários e exercitados. Os resultados obtidos mostram que, tal como nos animais sedentários, também os animais exercitados apresentaram uma elevada taxa de degradação de glicogénio, não se notando grande impacto do exercício no metabolismo da glucose. Também o metabolismo dos aminoácidos permaneceu inalterado. No entanto, o grupo exercitado mostrou alterações que sugerem um aumento da beta-oxidação de ácidos gordos e da fosforilação oxidativa, bem como o restabelecimento do metabolismo de corpos cetónicos. Globalmente, este trabalho demonstrou que o exercício físico tem um impacto positivo no metabolismo do gastrocnemius suportando assim a sua prescrição supervisionada a pacientes com ICFEP.2019-122019-12-01T00:00:00Z2021-12-13T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/30039engSantos, Inês Margarida Chavesinfo:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-02-22T11:58:09Zoai:ria.ua.pt:10773/30039Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:02:16.469168Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Effect of exercise training in skeletal muscle remodeling in heart failure with preserved ejection fraction |
title |
Effect of exercise training in skeletal muscle remodeling in heart failure with preserved ejection fraction |
spellingShingle |
Effect of exercise training in skeletal muscle remodeling in heart failure with preserved ejection fraction Santos, Inês Margarida Chaves Heart failure with preserved ejection fraction Exercise training Skeletal muscle Metabolism |
title_short |
Effect of exercise training in skeletal muscle remodeling in heart failure with preserved ejection fraction |
title_full |
Effect of exercise training in skeletal muscle remodeling in heart failure with preserved ejection fraction |
title_fullStr |
Effect of exercise training in skeletal muscle remodeling in heart failure with preserved ejection fraction |
title_full_unstemmed |
Effect of exercise training in skeletal muscle remodeling in heart failure with preserved ejection fraction |
title_sort |
Effect of exercise training in skeletal muscle remodeling in heart failure with preserved ejection fraction |
author |
Santos, Inês Margarida Chaves |
author_facet |
Santos, Inês Margarida Chaves |
author_role |
author |
dc.contributor.author.fl_str_mv |
Santos, Inês Margarida Chaves |
dc.subject.por.fl_str_mv |
Heart failure with preserved ejection fraction Exercise training Skeletal muscle Metabolism |
topic |
Heart failure with preserved ejection fraction Exercise training Skeletal muscle Metabolism |
description |
Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome characterized by pulmonary congestion, dyspnea, elevated left ventricular filling pressures, normal left ventricular ejection fraction (LVEF ≥ 50%) and exercise intolerance. Although it is an increasingly common syndrome, its treatment remains quite limited, with available therapies focusing mostly on symptom relief. Intolerance to exercise training is one of the main symptoms presented by patients with HFpEF. Due to the known benefits of exercise training at cardiovascular levels, it has been recommended as adjuvant non-pharmacological therapy in the treatment of HFpEF. Indeed, the benefits of exercise training have already been documented in HFpEF, however the molecular mechanisms underlying those benefits remain poorly understood. Thus, this study aimed to study the molecular changes underlying exercise training effects in HFpEF. An animal model of HFpEF was used, namely obese ZSF1 rats. The animals were submitted to a treadmill exercise protocol for 4 weeks, after which exercise intolerance test and hemodynamic evaluation were performed. After animal sacrifice, the gastrocnemius muscle was collected for metabolic analysis by Nuclear Magnetic Resonance Spectroscopy and Western Blot protein expression evaluation. Comparison between the metabolic profiles of gastrocnemius of ZSF1 obese rats and ZSF1 lean (control) rats allowed to characterize the changes inherent to the disease. The results show that HFpEF promoted glycogen degradation in small oligosaccharides, resulting in the release of glucose-1-phosphate, as well as glucose-6-phosphate and glucose accumulation. In addition, decreased AMPK expression, impaired metabolism of ketone bodies and increased metabolism of amino acids such as glutamine and glutamate were also observed in the sedentary HFpEF group. The impact of exercise on gastrocnemius metabolism of this animal model was evaluated by comparing sedentary and exercised obese animals. The results obtained show that, as in sedentary animals, the exercised animals also showed a high rate of glycogen degradation, with no significant impact of exercise on glucose metabolism. Also, amino acid metabolism remained unchanged. However, the exercised group showed changes that suggest an increment in fatty acid betaoxidation and oxidative phosphorylation, as well as the reestablishment of ketone body metabolism. Overall, this work has shown that exercise has a positive impact on gastrocnemius metabolism thus supporting its supervised prescription to patients with HFpEF. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-12 2019-12-01T00:00:00Z 2021-12-13T00:00:00Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/masterThesis |
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http://hdl.handle.net/10773/30039 |
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eng |
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