Cited by 148Autophagy in Disease and TherapyMuscle Physiology and DisordersExercise and Physiological Responses

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Higher activation of autophagy in skeletal muscle of mice during endurance exercise in the fasted state

Jamart, Cécile, Naslain, Damien, Gilson, Hélène, Francaux, Marc·2013·American Journal of Physiology-Endocrinology and Metabolism

DOI 10.1152/ajpendo.00270.2013

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Abstract

Activation of autophagy in skeletal muscle has been reported in response to endurance exercise and food deprivation independently. The purpose of this study was to evaluate whether autophagy was more activated when both stimuli were combined, namely when endurance exercise was performed in a fasted rather than a fed state. Mice performed a low-intensity running exercise (10 m/min for 90min) in both dietary states after which the gastrocnemius muscles were removed. LC3b-II, a marker of autophagosome presence, increased in both conditions, but the increase was higher in the fasted state. Other protein markers of autophagy, like Gabarapl1-II and Atg12 conjugated form as well as mRNA of Lc3b, Gabarapl1, and p62/Sqstm1 were increased only when exercise was performed in a fasted state. The larger activation of autophagy by exercise in a fasted state was associated with a larger decrease in plasma insulin and phosphorylation of Akt Ser473, Akt Thr308, FoxO3a Thr32, and ULK1 Ser757. AMPKα Thr172, ULK1 Ser317, and ULK1 Ser555 remained unchanged in both conditions, whereas p38 Thr180/Tyr182 increased during exercise to a similar extent in the fasted and fed conditions. The marker of mitochondrial fission DRP1 Ser616 was increased by exercise independently of the nutritional status. Changes in mitophagy markers BNIP3 and Parkin suggest that mitophagy was increased during exercise in the fasted state. In conclusion, our results highlight a major implication of the insulin-Akt-mTOR pathway and its downstream targets FoxO3a and ULK1 in the larger activation of autophagy observed when exercise is performed in a fasted state compared with a fed state.

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Authors: Jamart, C., Naslain, D., Gilson, H., & Francaux, M.
Affiliations: UCLouvain (BE)
Corresponding author: Francaux, Marc
ORCID: Francaux, Marc
Venue: American Journal of Physiology-Endocrinology and Metabolism
Publisher: American Physiological Society
Published: 2013-10-15
Volume: 305
Issue: 8
Pages: E964-E974
ISSN: 0193-1849 (ISSN-L)
1522-1555
DOI: 10.1152/ajpendo.00270.2013
OpenAlex: W2158565718
Cited by: 148
References: 55
Citations by year: 2026: 1 · 2025: 4 · 2024: 7 · 2023: 5 · 2022: 19 · 2021: 16 · 2020: 12 · 2019: 10 · 2018: 17 · 2017: 17 · 2016: 15 · 2015: 17 · 2014: 6 · 2013: 2
FWCI: 9.72
Type: journal article
Language: en
Open access: closed
Locations: American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
PubMed (publishedVersion)
Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion)
Funders: Fondation Louvain
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
Keywords: autophagy, endurance exercise, fasting, skeletal muscle, gastrocnemius, FOXO3, ULK1, mitophagy, Drp1, AMPK, p38 MAPK, GABARAPL1, LC3B, p62, food deprivation
MeSH terms: Sequestosome-1 Protein, Animals, Autophagy, Fasting, Female, Heat-Shock Proteins, Membrane Proteins, Mice, Inbred C57BL, Microtubule-Associated Proteins, Motor Activity, Physical Endurance, RNA, Messenger, Signal Transduction, Biomarkers, Up-Regulation, Muscle, Skeletal, Cytoplasmic Vesicles, Mitochondrial Proteins, Dynamins, Adaptor Proteins, Signal Transducing, Mice, Mitochondrial Dynamics

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Higher activation of autophagy in skeletal muscle of mice during endurance exercise in the fasted state

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