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

Abstract

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.

Polyamines and Physical Activity in Musculoskeletal Diseases: A Potential Therapeutic Challenge

“…The main aim of the current review was to discuss the effects of polyamines and physical activity on musculoskeletal diseases. To the best of our knowledge, while few studies [ 160 , 170 ] reported that spermidine supplementation in mice models improves autophagy in aged or defected muscle, more numerous studies revealed that exercise intervention promotes the autophagy and mitophagy processes in the skeletal muscle through the regulation of muscle remodeling and homeostasis, and by promoting aged skeletal muscle repairing and hypertrophy [ 53 , 54 , 55 , 56 , 57 , 58 , 59 ].…”

“…Moreover, direct evidence was provided for skeletal muscle by Laker et al and Wang et al [ 54 , 59 ], who proved that exercise respectively induced mitophagy in C57BL/6J mice and autophagy in ICR/CD-1 mice, both conventional murine models, through AMPK signaling. In addition, in the same aged murine model (C57BL/6J), not only ULK1 was found to increase, but also Atg5, Atg7, and LC3-II when exercise was administrated [ 55 ].…”

“…Among these natural compounds, polyamines represent autophagy-stimulating molecules that have attracted great attention in the last decade. Another interesting and safe modulator that was recently identified as an autophagy inducer in vivo is physical exercise [ 53 , 54 , 55 , 56 , 57 , 58 , 59 ]. Indeed, proper tuning of autophagy and mitophagy extent by selected “modulators”, such as safe nutraceuticals, for instance, polyamines and physical exercise, are an attractive emerging objective to limit aging-induced muscle atrophy [ 60 , 61 ], which is the major focus of the present narrative review.…”

Autophagy and Exercise: Current Insights and Future Research Directions

“…Rodent studies assessing skeletal muscle adaptations have provided convincing evidence of an exercise-induced increase in autophagy initiation signaling, such as phosphorylation of ULK1 at S317 and S555 [43,44] and disruption of the BCL2-BECN1 inhibitory complex [22]. Moreover, a robust increase in markers of autophagosome content (e. g. [22,44,45]) and autophagy flux [22] following a single endurance exercise session in skeletal muscle is often reported in rodents [46][47][48], and is disrupted in mouse models of muscle dystrophy [49]. The increase in autophagosome content seems to be observed following at least 30 min of exercise [16,22] and to be independent of exercise intensity [44].…”

“…The increase in autophagosome content seems to be observed following at least 30 min of exercise 16 22 and to be independent of exercise intensity 44 . The protein abundance of the autophagy receptor p62 has been shown to be decreased 22 44 45 or unchanged 46 50 51 following exercise in rodents. These findings have supported the widely accepted notion that endurance exercise increases autophagy in skeletal muscle.…”