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

Abstract

The protective effects of chronic moderate exercise-mediated autophagy include the prevention and treatment of several diseases and the extension of lifespan. In addition, physical exercise may impair cellular structures, requiring the action of the autophagy mechanism for clearance and renovation of damaged cellular components. For the first time, we investigated the adaptations on basal autophagy flux in vivo in mice’s liver, heart, and skeletal muscle tissues submitted to four different chronic exercise models: endurance, resistance, concurrent, and overtraining. Measuring the autophagy flux in vivo is crucial to access the functionality of the autophagy pathway since changes in this pathway can occur in more than five steps. Moreover, the responses of metabolic, performance, and functional parameters, as well as genes and proteins related to the autophagy pathway, were addressed. In summary, the regular exercise models exhibited normal/enhanced adaptations with reduced autophagy-related proteins in all tissues. On the other hand, the overtrained group presented higher expression of Sqstm1 and Bnip3 with negative morphological and physical performance adaptations for the liver and heart, respectively. The groups showed different adaptions in autophagy flux in skeletal muscle, suggesting the activation or inhibition of basal autophagy may not always be related to improvement or impairment of performance.

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

“…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 ].…”

“…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 ].…”

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

“…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.…”

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

“…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.…”

“…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).…”