Moderate, but Not Excessive, Training Attenuates Autophagy Machinery in Metabolic Tissues

Rocha, Aristides Almeida; Pinto, Ana P.; Morais, Gustavo P.; Marafon, Bruno B.; Rovina, Rafael L.; Veras, Allice Santos Cruz; Teixeira, Giovana Rampazzo; Pauli, José Rodrigo; Moura, Leandro Pereira de; Cintra, Dennys Esper; Ropelle, Eduardo Rochete; Rivas, Donato A.; Silva, Adelino Sánchez Ramos da

doi:10.3390/ijms21228416

Cited by 14 publications

(13 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, future investigations should compare these physical exercise protocols’ effects considering other skeletal muscle samples and time courses. It is essential to point out that the autophagic flux responses to chronic strength and concurrent exercise protocols have been investigated [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

“…Mice were treated with intraperitoneal injections of colchicine (0.4 mg/kg/day; AB120663, ABCAM, Cambridge, UK) or vehicle (0.9% saline) for 3 consecutive days. The final injection was performed 4 h before the acute physical exercise protocols [ 44 , 68 , 69 , 70 ]. The colchicine treatment inhibits autophagosome degradation, inducing an increase in the levels of LC3II and/or Sqstm1/p62 [ 71 ].…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Impact of Different Physical Exercises on the Expression of Autophagy Markers in Mice

Pinto

Rocha

Marafon

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

Although physical exercise-induced autophagy activation has been considered a therapeutic target to enhance tissue health and extend lifespan, the effects of different exercise models on autophagy in specific metabolic tissues are not completely understood. This descriptive investigation compared the acute effects of endurance (END), exhaustive (ET), strength (ST), and concurrent (CC) physical exercise protocols on markers of autophagy, genes, and proteins in the gastrocnemius muscle, heart, and liver of mice. The animals were euthanized immediately (0 h) and six hours (6 h) after the acute exercise for the measurement of glycogen levels, mRNA expression of Prkaa1, Ppargc1a, Mtor, Ulk1, Becn1, Atg5, Map1lc3b, Sqstm1, and protein levels of Beclin 1 and ATG5. The markers of autophagy were measured by quantifying the protein levels of LC3II and Sqstm1/p62 in response to three consecutive days of intraperitoneal injections of colchicine. In summary, for gastrocnemius muscle samples, the main alterations in mRNA expressions were observed after 6 h and for the ST group, and the markers of autophagy for the CC group were increased (i.e., LC3II and Sqstm1/p62). In the heart, the Beclin 1 and ATG5 levels were downregulated for the ET group. Regarding the markers of autophagy, the Sqstm1/p62 in the heart tissue was upregulated for the END and ST groups, highlighting the beneficial effects of these exercise models. The liver protein levels of ATG5 were downregulated for the ET group. After the colchicine treatment, the liver protein levels of Sqstm1/p62 were decreased for the END and ET groups compared to the CT, ST, and CC groups. These results could be related to diabetes and obesity development or liver dysfunction improvement, demanding further investigations.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Impact of Different Physical Exercises on the Expression of Autophagy Markers in Mice

Pinto

Rocha

Marafon

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, Kim et al reported that expressions of LC3II/LC3I was decreased after a single bout of exercise 7 . And Alisson et al reported that chronic exhaustive training reduced the LC3II protein expression 38 . There are several possible explanations for these discrepancies.…”

Section: Discussionmentioning

confidence: 99%

A single bout of exhaustive treadmill exercise increased AMPK activation associated with enhanced autophagy in mice skeletal muscle

Wang

Zhou

et al. 2022

Clin Exp Pharma Physio

View full text Add to dashboard Cite

Previous studies reported inconsistent findings on autophagy activation in skeletal muscles after acute exercise. In this study, we investigated the effect of a single bout of exhaustive treadmill exercise on AMPK and autophagy activations in mice gastrocnemius muscle in vivo. Male ICR/CD‐1 mice were randomly divided into the control and exercise groups. The later was subjected to a single bout of exhaustive treadmill exercise. Changes of AMPK, phosphorylation of AMPKThr172 (pAMPKThr172), and autophagy markers including Beclin1, LC3II/LC3I and p62 mRNA and protein expressions in gastrocnemius muscle at different times (0, 6, 12, 24 h) after the exercise were analysed by quantitative real‐time PCR and western blot. Our results demonstrated that a single bout of exhaustive treadmill exercise significantly induced AMPK content and AMPK activity at 0, 6 and 12 h after the exercise, and changed the expressions of autophagy markers at different time points in the recovery period, respectively. Moreover, we observed positive correlations between expressions of LC3II/LC3I ratio and pAMPKThr172 or AMPK, and a negative correlation between expressions of p62 and AMPK or pAMPKThr172. In conclusion, a single bout of exhaustive treadmill exercise in mice caused a prolonged activation of AMPK and improved autophagy in the gastrocnemius muscle. The regulation of autophagic markers were related to enhanced AMPK activity. The findings indicate that acute exercise enhanced AMPK‐related autophagy activation may be the underlying molecular mechanism that regulates cellular energy metabolism during exercise.

show abstract

“…Portanto, os níveis elevados de insulina para o grupo EE/Rapa podem explicar os níveis mais elevados Diversas investigações utilizando diferentes condições de saúde demonstraram elevação dos marcadores de autofagia no tecido hepático e nas células hepáticas após o tratamento com rapamicina(99)(100)(101)(102)(103), porém é a primeira vez que a combinação entre excesso de exercício e rapamicina é investigada. da Rocha et al(80) demonstraram a redução de vários genes autofágicos no fígado de camundongos submetidos aos protocolos de endurance ou excessivo. Os autores concluíram que o exercício regular de endurance é um fator epigenético que modifica as expressões gênicas autofágicas no fígado a um novo estado basal(80).Para analisar o fluxo autofágico, os roedores receberam colchicina, uma droga bloqueadora do autofagossomo que aumenta o conteúdo de Sqstm1/p62 e LC3 II.…”

unclassified

“…da Rocha et al(80) demonstraram a redução de vários genes autofágicos no fígado de camundongos submetidos aos protocolos de endurance ou excessivo. Os autores concluíram que o exercício regular de endurance é um fator epigenético que modifica as expressões gênicas autofágicas no fígado a um novo estado basal(80).Para analisar o fluxo autofágico, os roedores receberam colchicina, uma droga bloqueadora do autofagossomo que aumenta o conteúdo de Sqstm1/p62 e LC3 II. A ativação autofágica hepática preserva os hepatócitos da morte e lesão celular(104).…”

unclassified

Mecanismos moleculares relacionados ao aumento do conteúdo hepático de gordura em resposta ao excesso de exercício físico

Pinto¹

View full text Add to dashboard Cite

O exercício excêntrico excessivo levou ao acúmulo de gordura hepática, o que ocorreu concomitantemente com a elevação das principais proteínas do complexo 1 do alvo da rapamicina em mamíferos (mTORC1) e da via de sinalização da insulina. Uma vez que a mTORC1 e a insulina podem inibir a via da autofagia e explicar a elevação do conteúdo de lipídio no fígado, o principal objetivo da presente investigação foi verificar a resposta dos genes e proteínas relacionados as vias da autofagia e lipogênese no tecido hepático de camundongos submetidos ao protocolo de corrida excessivo em declive com e sem a administração de rapamicina, uma droga que inibe a via da mTORC1. Camundongos C57BL/6 foram divididos em quatro grupos experimentais: Controle (CT; sedentário), Excesso de exercício físico em declive (EE), Excesso de exercício físico em declive com administração crônica de rapamicina (EE/Rapa) e Endurance (END). Ao final do protocolo de 8 semanas de exercício, o sangue e o fígado foram coletados para análise sérica, histologia, imunohistoquímica, conteúdo de gordura hepática, reação em cadeia da polimerase em tempo real e immunoblotting. Os principais resultados foram: 1) elevação dos níveis de glicose, insulina, HOMA-IR, cortisol, ALT e colesterol, mas níveis mais baixos de T4 para o grupo EE/Rapa; 2) acúmulo de gordura hepática para os grupos EE e EE/Rapa; 3) aumento de LC3 por imunoexpressão e diminuição dos genes autofágicos para os grupos EE, EE/Rapa e END; 4) redução da fosforilação de p70S6K e aumento da fosforilação de Foxo1A para o grupo EE/Rapa. Em resumo, o exercício excessivo com ou sem rapamicina levou ao aumento do conteúdo de gordura no fígado. Embora a rapamicina tenha sido eficaz na inibição de mTOR, a via da autofagia não foi regulada positivamente.

show abstract

Moderate, but Not Excessive, Training Attenuates Autophagy Machinery in Metabolic Tissues

Cited by 14 publications

References 49 publications

Impact of Different Physical Exercises on the Expression of Autophagy Markers in Mice

Impact of Different Physical Exercises on the Expression of Autophagy Markers in Mice

A single bout of exhaustive treadmill exercise increased AMPK activation associated with enhanced autophagy in mice skeletal muscle

Mecanismos moleculares relacionados ao aumento do conteúdo hepático de gordura em resposta ao excesso de exercício físico

Contact Info

Product

Resources

About