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

Pinto, Ana P.; Rocha, Aristides Almeida; Marafon, Bruno B.; Rovina, Rafael L.; Muñoz, Vitor Rosetto; Silva, Lilian E.C.M. da; Pauli, José Rodrigo; Moura, Leandro Pereira de; Cintra, Dennys Esper; Ropelle, Eduardo Rochete; Silva, Adelino Sánchez Ramos da

doi:10.3390/ijms22052635

Cited by 19 publications

(25 citation statements)

References 71 publications

(52 reference statements)

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“…By contrast, 8 wk of swimming training has been shown to increase autophagy flux in mouse triceps muscles (20). In the present study, the LC3-II flux was decreased significantly after acute downhill running, which is contrary to a previous study in which autophagic flux was unchanged after a bout of exhaustive downhill running (25). The discrepancy may arise from animal or muscle choice and the timing of postexercise sampling.…”

Section: Discussioncontrasting

confidence: 99%

Downhill Running Decreases the Acetylation of Tubulins and Impairs Autophagosome Degradation in Rat Skeletal Muscle

Wang

Niu²,

Lei

et al. 2021

Medicine &Amp; Science in Sports &Amp; Exercise

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PurposeThis study was designed to probe the effect of downhill running on microtubule acetylation and autophagic flux in rat skeletal muscle.MethodsSprague–Dawley rats were subjected to an exercise protocol of a 90-min downhill run with a slope of −16° and a speed of 16 m·min−1, and then the soleus was sampled at 0, 12, 24, 48, and 72 h after exercise. Protein expression levels of microtubule-associated protein 1 light chain 3 (LC3), p62/sequestosome 1 (p62), α-tubulin, and acetylated α-tubulin (AcK40 α-tubulin) were detected by Western blotting. Alpha-tubulin was costained with AcK40 α-tubulin or cytoplasmic dynein intermediate chain in a single muscle fiber, and LC3 was costained with lysosomal-associated membrane protein 1 in cryosections. To assess autophagic flux in vivo, colchicine or vehicle was injected intraperitoneally 3 d before the exercise experiment, and the protein levels of LC3 and p62 were measured by Western blotting.ResultsDownhill running induced a significant increase in the protein levels of LC3-II and p62, whereas the level and proportion of AcK40 α-tubulin were markedly decreased. Furthermore, the amount of dynein on α-tubulin was decreased after downhill running, and autophagosomes accumulated in the middle of myofibrils. Importantly, LC3-II flux was decreased after downhill running compared with that in the control group.ConclusionsA bout of downhill running decreases microtubule acetylation, which may impair dynein recruitment and autophagosome transportation, causing blocked autophagic flux.

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Section: Discussioncontrasting

confidence: 99%

Downhill Running Decreases the Acetylation of Tubulins and Impairs Autophagosome Degradation in Rat Skeletal Muscle

Wang

Niu²,

Lei

et al. 2021

Medicine &Amp; Science in Sports &Amp; Exercise

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“…The increase in LC3B‐II by exercise could result from either an induction of autophagy or a block in the turnover of LC3B‐II‐bound autophagosomes. For instance, administration with colchicine, an inhibitor of autophagosome–lysosome fusion that directly blocks autophagy flux in skeletal muscle, significantly increases the proteins levels of LC3‐II and p62 in skeletal muscle of exercise mice 26 . To distinguish between these possibilities, we detected the turnover of p62/SQSTM1.…”

Section: Resultsmentioning

confidence: 99%

Physical exercise attenuates age‐related muscle atrophy and exhibits anti‐ageing effects via the adiponectin receptor 1 signalling

Chen

Tang

et al. 2023

J cachexia sarcopenia muscle

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Background Although the adiponectin signalling exerts exercise‐mimicking effects, whether this pathway contributes to the anti‐ageing benefits of physical exercise has not been established yet. Methods Swim exercise training and wheel running were used to measure lifespan in the nematode Caenorhabditis elegans and skeletal muscle quality in mice, respectively. Muscle weight, muscle fibre cross‐sectional area (CSA) and myonuclei number were used to evaluate muscle mass. RNA sequencing (RNA‐Seq) analysis of skeletal muscle in exercised mice was used to study the underlying mechanisms. Western blot and immunofluorescence were performed to explore autophagy‐ and senescence‐related markers. Results The C. elegans adiponectin receptor PAQR‐1/AdipoR1, but not PAQR‐2/AdipoR2, was activated (3.55‐fold and 3.48‐fold increases in p‐AMPK on Days 1 and 6, respectively, P < 0.001), which was involved in lifespan extension in exercised worms. Exercise training increased skeletal muscle mass index (1.29‐fold, P < 0.01), muscle weight (1.75‐fold, P < 0.001), myonuclei number (1.33‐fold, P < 0.05), muscle fibre CSA (1.39‐fold, P < 0.05) and capillary abundance (2.19‐fold, P < 0.001 for capillary density; 1.58‐fold, P < 0.01 for capillary number) in aged mice. Physical exercise reduced protein (2.94‐fold, P < 0.001) and mRNA levels (1.70‐fold, P < 0.001) of p16INK4a, a marker for cellular senescence, in skeletal muscle of aged mice. These beneficial effects of exercise on skeletal muscle of mice were dependent on AdipoR1. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis for differentially expressed genes in skeletal muscle between exercised mice with and without AdipoR1 knockdown by RNA‐Seq analysis revealed that several KEGG pathways, such as ‘AMPK signalling pathway’ (P < 0.001), ‘FOXO signalling pathway’ (P < 0.001) and ‘autophagy’ (P < 0.001) were overrepresented. Knockdown of FoxO3a inhibited exercise‐mediated beneficial effects on skeletal muscle quality of mice by inhibiting autophagy/mitophagy (3.81‐fold reduction in LC3‐II protein, P < 0.001; 1.53‐fold reduction in BNIP3 protein, P < 0.05). Knockdown of daf‐16, the FoxO homologue in C. elegans, reduced autophagy (2.77‐fold and 2.06‐fold reduction in GFP::LGG‐1 puncta in seam cells and the intestine, respectively, P < 0.05) and blocked lifespan extension by exercise in worms. Conclusions Our findings provide insights into how the AdipoR1 pathway has an impact on the anti‐ageing benefits of exercise and implicate that activation of the AdipoR1 signalling may represent a potential therapeutic strategy for reducing age‐related loss of skeletal muscle.

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“…However, it has also been found that different types of exercise may regulate autophagy in skeletal muscles differently, which may be related to the mode of exercise, including exercise intensity and time course, and biological markers studied. For example, a swimming exercise increased expression of autophagy markers Beclin1, LC3II and the ratio of LC3II/LC3I, but not LC3I and p62 in skeletal muscle of mice, 3 while moderate cycling and exhaustive treadmill running exercise did not change expression of LC3II and p62 proteins in skeletal muscle of human and mice 2,4 . In addition, acute resistance exercise did not change the expression of p62 mRNA and Beclin1 and LC3II/LC3I protein 5 …”

Section: Introductionmentioning

confidence: 98%

“…It has been established that the increase of energy demand during the exercise result in increase of AMP:ATP ratio and stimulation of adenosine monophosphate (AMP) activated protein kinase (AMPK) which plays a key role in maintaining skeletal muscle function 4,8,10 . On the other hand, there is also evidence that muscle contraction may activate AMP/AMPK signalling, through downstream cascades, modulates autophagy as part of a complex mechanism to restore cellular homeostasis 4,11,12 . However, the link between AMPK and autophagy in exercise is still controversial and especially the change of these mechanisms in the recovery phase of exercise.…”

Section: Introductionmentioning

confidence: 99%

“…However, the link between AMPK and autophagy in exercise is still controversial and especially the change of these mechanisms in the recovery phase of exercise. For example, it has been shown that acute exercise activated autophagic activity, 4‐10 however, Liu et al reported no change of phosphorylation of AMPK (pAMPK) after exhaustive treadmill exercise, 13 while Halling et al reported an increase of pAMPK after a treadmill exercise 14 . In addition, it has been suggested that high‐intensity cycling exercise may induce AMPK activation and increase autophagy in human vastus lateralis 15 .…”

Section: Introductionmentioning

confidence: 99%

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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

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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.

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

Cited by 19 publications

References 71 publications

Downhill Running Decreases the Acetylation of Tubulins and Impairs Autophagosome Degradation in Rat Skeletal Muscle

Downhill Running Decreases the Acetylation of Tubulins and Impairs Autophagosome Degradation in Rat Skeletal Muscle

Physical exercise attenuates age‐related muscle atrophy and exhibits anti‐ageing effects via the adiponectin receptor 1 signalling

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

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