Efeitos do exercício aeróbico no músculo esquelético de ratos adultos submetidos à restrição proteica perinatal
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Data
2023-02-24
Autores
Valente, Jéssica Silvino
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
O tecido muscular possui uma capacidade de modulação fenotípica frente a diferentes estímulos (positivos ou negativos), alterando suas características metabólicas, funcionais e morfológicas. Sendo o maior órgão metabólico de armazenamento energético do corpo e de grande importância para locomoção e sustentação corporal, o entendimento da influência de estímulos diretos para essas características é de alta relevância. A restrição proteica materna (RPM) durante os estágios iniciais da vida (gestação e/ou lactação) leva a alterações no desenvolvimento fetal e adaptações fisiológicas da prole durante toda a vida, as quais envolvem distúrbios metabólicos sistêmicos, como obesidade e diabetes, além de alterações em diversos sistemas, como o músculo estriado esquelético. Por outro lado, sabe-se que a prática regular de exercício físico é benéfica para o organismo em resposta a diferentes doenças, sendo possível sua utilização como estratégia terapêutica para as alterações musculares derivadas da RPM. O objetivo deste trabalho foi analisar os efeitos do exercício físico aeróbico (EFA) nos músculos Sóleo (SOL), com metabolismo oxidativo/contração lenta, e Plantar (PL), com metabolismo glicolítico/contração rápida, em ratos adultos submetidos à RPM nos períodos de gestação e lactação. Foram utilizados ratos machos Sprague Dawley, provenientes de genitoras submetidas às dietas normocalóricas proteicas padrão (17%-controle) ou hipoproteica (6%-restrito) durante toda gestação e lactação. No dia pós-natal (DPN) 90, os animais foram divididos nos grupos experimentais: Controle Sedentário (CS); Controle Treinado (CT); Restrito Sedentário (RS) e Restrito Treinado (RT). Os animais dos grupos treinados foram submetidos ao protocolo de EFA de natação (oito semanas) com tempo/carga progressivos semanalmente, até completar as primeiras três semanas, com tempo/carga máxima nas últimas cinco semanas. No DPN 150, os animais foram anestesiados e sacrificados (morte humanitária), amostras dos músculos SOL e PL foram coletadas e processadas para as análises morfométrica (n=8), molecular (n=8), bioquímica (n=8) e proteômica (n=3). Os animais foram pesados durante todo o protocolo experimental (DPN 0, 21, 90, 120 e 150), e o teste oral de tolerância a glicose oral (TOTG) foi realizado no DPN 150. Os animais do grupo RS apresentaram um ganho de peso maior que os animais dos grupos controles (CS e CT), o qual foi menos acentuado nos animais RT. Os animais do grupo RS (vs CS) mantiveram as concentrações de glicose sanguínea elevada durante todo o TOTG, e aos 60min, os níveis glicêmicos foram reduzidos nos animais do grupo RT (vs RS). Os músculos SOL e PL apresentaram aumento na área de secção transversal das fibras musculares nos grupos RS (vs CS) e uma diminuição nos animais RT (vs RS). O músculo SOL apresentou uma diminuição na expressão gênica dos marcadores catabólicos Mafbx e Murf1 nos grupos RS (vs CS), e o grupo RT (vs RS) apresentou aumento no mRNA Mafbx e diminuição na expressão do marcador catabólico Igf1; a expressão gênica dos marcadores de metabolismo oxidativo Cs e glicolítico Ldha diminuiu nos animais dos grupos CT e RS (vs CS). Não foram observadas diferenças estatísticas nos genes analisados, no músculo PL. A análise de glicogênio muscular mostrou aumento nos níveis, nos animais do grupo RS, seguido de diminuição nos animais do grupo RT no músculo SOL, sem alterações no músculo PL. A análise do Proteoma apontou 57 e 33 proteínas diferencialmente expressas, no músculo SOL e PL, respectivamente, comuns entre as comparações CTxCS, RSxCS e RTxRS, as quais enriqueceram majoritariamente, o metabolismo energético muscular, com destaque para a via da glicólise e glicogênio. Concluímos que a RPM causou o efeito de crescimento acelerado corporal e muscular, levou à diminuição da oxidação da glicose com acúmulo de glicogênio no músculo SOL, e exacerbou a oxidação da glicose e o catabolismo do glicogênio no músculo PL. O EFA atenuou o efeito de crescimento acelerado e as alterações metabólicas glicolíticas no músculo SOL, intensificando esta via, no músculo PL.
Muscle tissue has a capacity for phenotypic modulation due to different stimuli (positive or negative), changing its metabolic, functional, and morphological characteristics. The skeletal muscle is the most significant metabolic organ for amino acid storage and, it has significant importance for locomotion and body support. Thus, understanding the influence of direct stimuli on muscle characteristics is highly relevant. Maternal protein restriction (MPR) during the early stages of life (pregnancy and/or lactation) leads to changes in fetal development and physiological adaptations in offspring throughout life, which involve systemic metabolic disorders such as obesity and diabetes, in addition to changes in several systems, such as skeletal muscle. On the other hand, it is known that regular physical exercise is beneficial for the body in response to different pathologies, making it possible to use as a therapeutic strategy for muscle alterations derived from MPR. The aim of this study was to analyze the effects of aerobic exercise (AE) on the Soleus (SOL) muscle which possesses oxidative metabolism/slow contraction, and Plantar (PL) muscle which has glycolytic metabolism/fast contraction, in adult rats submitted to MPR during pregnancy and lactation. Male Sprague Dawley rats from mothers submitted to norm caloric protein (17%-control) or low-protein (6%-restricted) diets throughout pregnancy and lactation were used. On a postnatal day (PD) 90, the animals were divided into experimental groups: Sedentary Control (SC); Trained Control (TC); Sedentary Restricted (SR) and Trained Restricted (TR). The animals of the trained groups were submitted to the AE protocol of swimming (8 weeks) with progressive time/load weekly, until completing the first 3 weeks, with maximum time/load in the last 5 weeks. At PD 150, the animals were anesthetized and sacrificed (humane death), and samples of the SOL and PL muscles were collected and processed for morphometric (n=8), molecular (n=8), biochemical (n=8) and proteomic (n=3) analyzes. The animals were weighed throughout the experimental protocol (PD 0, 21, 90, 120, and 150), and the oral glucose tolerance test (OGTT) was performed at PD 150. The animals in the SR group showed a superior weight gain compared to the animals of the control groups (SC and TC), and this parameter was less pronounced in the TR animals. The animals in the SR group (vs SC) maintained high blood glucose concentrations throughout the OGTT, and at 60 min the glycemic levels were reduced in the animals of the TR group (vs SR). The cross-sectional area of muscle fibers in SOL and PL muscles increased in the SR groups (vs SC) and decreased in the TR animals (vs SR). The SOL muscle showed a decrease in the gene expression of the catabolic markers Mafbx and Murf1 in the SR groups (vs SC), and the TR group (vs SR) showed an increase in Mafbx mRNA and a decrease in the expression of the anabolic marker Igf1; gene expression of oxidative metabolism markers Cs and glycolytic Ldha decreased in animals from TC and SR groups (vs SC). No statistical differences were observed in the genes analyzed in the PL muscle. The muscle glycogen increased in the animals of the SR group, followed by a decrease in the animals of the TR group in the SOL muscle, without changes in the PL muscle. The Proteome analysis showed 57 and 33 differentially expressed proteins, in the SOL and PL muscle, respectively, common between the TCxSC, SRxSC, and TRxSR comparisons, which mostly enriched muscle energy metabolism, with emphasis on the glycolysis and glycogen pathway. We conclude that MPR caused the catch-up effect of body and muscle growth, led to decreased glucose oxidation with glycogen accumulation in the SOL muscle and intensified glucose oxidation and glycogen catabolism in the PL muscle. AE attenuated the catch-up growth effect and the glycolytic metabolic changes in the SOL muscle, intensifying the effects related to this pathway in the PL muscle.
Muscle tissue has a capacity for phenotypic modulation due to different stimuli (positive or negative), changing its metabolic, functional, and morphological characteristics. The skeletal muscle is the most significant metabolic organ for amino acid storage and, it has significant importance for locomotion and body support. Thus, understanding the influence of direct stimuli on muscle characteristics is highly relevant. Maternal protein restriction (MPR) during the early stages of life (pregnancy and/or lactation) leads to changes in fetal development and physiological adaptations in offspring throughout life, which involve systemic metabolic disorders such as obesity and diabetes, in addition to changes in several systems, such as skeletal muscle. On the other hand, it is known that regular physical exercise is beneficial for the body in response to different pathologies, making it possible to use as a therapeutic strategy for muscle alterations derived from MPR. The aim of this study was to analyze the effects of aerobic exercise (AE) on the Soleus (SOL) muscle which possesses oxidative metabolism/slow contraction, and Plantar (PL) muscle which has glycolytic metabolism/fast contraction, in adult rats submitted to MPR during pregnancy and lactation. Male Sprague Dawley rats from mothers submitted to norm caloric protein (17%-control) or low-protein (6%-restricted) diets throughout pregnancy and lactation were used. On a postnatal day (PD) 90, the animals were divided into experimental groups: Sedentary Control (SC); Trained Control (TC); Sedentary Restricted (SR) and Trained Restricted (TR). The animals of the trained groups were submitted to the AE protocol of swimming (8 weeks) with progressive time/load weekly, until completing the first 3 weeks, with maximum time/load in the last 5 weeks. At PD 150, the animals were anesthetized and sacrificed (humane death), and samples of the SOL and PL muscles were collected and processed for morphometric (n=8), molecular (n=8), biochemical (n=8) and proteomic (n=3) analyzes. The animals were weighed throughout the experimental protocol (PD 0, 21, 90, 120, and 150), and the oral glucose tolerance test (OGTT) was performed at PD 150. The animals in the SR group showed a superior weight gain compared to the animals of the control groups (SC and TC), and this parameter was less pronounced in the TR animals. The animals in the SR group (vs SC) maintained high blood glucose concentrations throughout the OGTT, and at 60 min the glycemic levels were reduced in the animals of the TR group (vs SR). The cross-sectional area of muscle fibers in SOL and PL muscles increased in the SR groups (vs SC) and decreased in the TR animals (vs SR). The SOL muscle showed a decrease in the gene expression of the catabolic markers Mafbx and Murf1 in the SR groups (vs SC), and the TR group (vs SR) showed an increase in Mafbx mRNA and a decrease in the expression of the anabolic marker Igf1; gene expression of oxidative metabolism markers Cs and glycolytic Ldha decreased in animals from TC and SR groups (vs SC). No statistical differences were observed in the genes analyzed in the PL muscle. The muscle glycogen increased in the animals of the SR group, followed by a decrease in the animals of the TR group in the SOL muscle, without changes in the PL muscle. The Proteome analysis showed 57 and 33 differentially expressed proteins, in the SOL and PL muscle, respectively, common between the TCxSC, SRxSC, and TRxSR comparisons, which mostly enriched muscle energy metabolism, with emphasis on the glycolysis and glycogen pathway. We conclude that MPR caused the catch-up effect of body and muscle growth, led to decreased glucose oxidation with glycogen accumulation in the SOL muscle and intensified glucose oxidation and glycogen catabolism in the PL muscle. AE attenuated the catch-up growth effect and the glycolytic metabolic changes in the SOL muscle, intensifying the effects related to this pathway in the PL muscle.
Descrição
Palavras-chave
Tecido muscular, Restrição proteica materna, Exercício físico aeróbico, Glicose, Análise proteômica, Muscle tissue, Maternal protein restriction, Aerobic exercise, Glucose, Proteomic analysis