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A novel gravity-induced blood flow restriction model augments ACC phosphorylation and PGC-1α mRNA in human skeletal muscle following aerobic exercise: a randomized crossover study

Publication: Applied Physiology, Nutrition, and Metabolism
28 November 2019


This study tested the hypothesis that a novel, gravity-induced blood flow restricted (BFR) aerobic exercise (AE) model will result in greater activation of the AMPK–PGC-1α pathway compared with work rate-matched non-BFR. Thirteen healthy males (age: 22.4 ± 3.0 years; peak oxygen uptake: 42.4 ± 7.3 mL/(kg·min)) completed two 30-min work rate-matched bouts of cycling performed with their legs below (CTL) and above their heart (BFR) at ∼2 weeks apart. Muscle biopsies were taken before, immediately, and 3 h after exercise. Blood was drawn before and immediately after exercise. Our novel gravity-induced BFR model led to less muscle oxygenation during BFR compared with CTL (O2Hb: p = 0.01; HHb: p < 0.01) and no difference in muscle activation (p = 0.53). Plasma epinephrine increased following both BFR and CTL (p < 0.01); however, only norepinephrine increased more following BFR (p < 0.01). PGC-1α messenger RNA (mRNA) increased more following BFR (∼6-fold) compared with CTL (∼4-fold; p = 0.036). VEGFA mRNA increased (p < 0.01) similarly following BFR and CTL (p = 0.21), and HIF-1α mRNA did not increase following either condition (p = 0.21). Phosphorylated acetyl-coenzyme A carboxylase (ACC) increased more following BFR (p < 0.035) whereas p-PKA substrates, p-p38 MAPK, and acetyl-p53 increased (p < 0.05) similarly following both conditions (p > 0.05). In conclusion, gravity-induced BFR is a viable BFR model that demonstrated an important role of AMPK signalling on augmenting PGC-1α mRNA.
Gravity-induced BFR AE reduced muscle oxygenation without impacting muscle activation, advancing gravity-induced BFR as a simple, inexpensive BFR model.
Gravity-induced BFR increased PGC-1α mRNA and ACC phosphorylation more than work rate-matched non-BFR AE.
This is the first BFR AE study to concurrently measure blood catecholamines, muscle activation, and muscle oxygenation.


Cette étude teste l’hypothèse selon laquelle un nouveau modèle d’exercice aérobie (« AE ») à restriction de débit sanguin (« BFR ») induit par la gravité suscite une plus grande activation de la voie AMPK–PGC-1α comparativement à un exercice apparié en intensité et sans BFR. Treize hommes en bonne santé (âge: 22,4 ± 3,0 ans; consommation d’oxygène de pointe: 42,4 ± 7,3 mL/(kg·min)) se soumettent ∼ 2 semaines d’intervalle à 2 séances de 30 minutes de cyclisme appariées en intensité dans deux conditions : avec leurs jambes au-dessous (« CTL ») et au-dessus de leur cœur (« BFR »). Des biopsies musculaires sont effectuées avant, immédiatement et 3 heures après l’exercice. Le sang est prélevé avant et immédiatement après l’exercice. Notre nouveau modèle de BFR induit par la gravité engendre une moindre oxygénation musculaire dans la condition BFR comparativement à la condition CTL (O2Hb : p = 0,01; HHb : p < 0,01) et ne suscite aucune différence d’activation musculaire (p = 0,53). L’épinéphrine plasmatique augmente dans les deux conditions BFR et CTL (p < 0,01), mais seule la norépinéphrine augmente davantage dans la condition BFR (p < 0,01). L’ARN messager (ARNm) de PGC-1α augmente davantage dans la condition BFR (environ 6 fois) comparativement à la condition CTL (environ 4 fois; p = 0,036). On observe une augmentation similaire de l’ARNm de VEGFA (p < 0,01) dans les conditions BFR et CTL (p = 0,21), mais on ne note pas d’augmentation de l’ARNm de HIF-1α dans les deux conditions (p = 0,21). L’acétyl-coenzyme A carboxylase (ACC) phosphorylée augmente davantage dans la condition BFR (p < 0,035) alors que les substrats de p-PKA, p-p38 MAPK et acétyl-p53 augmentent (p < 0,05) de manière similaire dans les deux conditions (p > 0,05). En conclusion, la BFR induite par la gravité est un modèle de BFR viable qui révèle le rôle important de la signalisation AMPK dans l’augmentation de l’ARNm de PGC-1α. [Traduit par la Rédaction]
Les nouveautés
L’exercice aérobie associé à la BFR induite par la gravité diminue l’oxygénation musculaire sans impacter l’activation musculaire, faisant ainsi la promotion de la BFR induite par la gravité en tant que modèle de BFR simple et peu coûteux.
La BFR induite par la gravité augmente l’ARNm de PGC-1α et la phosphorylation de l’ACC plus que l’exercice aérobie sans BFR apparié en intensité.
Cette recherche est la première étude à propos de l’exercice aérobie associé à la BFR visant à mesurer simultanément les catécholamines sanguines, l’activation musculaire et l’oxygénation musculaire.

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cover image Applied Physiology, Nutrition, and Metabolism
Applied Physiology, Nutrition, and Metabolism
Volume 45Number 6June 2020
Pages: 641 - 649


Received: 4 September 2019
Accepted: 19 November 2019
Accepted manuscript online: 28 November 2019
Version of record online: 28 November 2019


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Key Words

  1. PGC-1a
  2. blood flow restriction
  3. aerobic exercise
  4. AMPK signalling
  5. BFR
  6. gene expression
  7. muscle oxygenation
  8. EMG
  9. catecholamines
  10. cycling


  1. PGC-1α
  2. restriction du flux sanguin
  3. exercice aérobie
  4. signalisation de l’AMPK
  5. BFR
  6. expression génique
  7. oxygénation musculaire
  8. EMG
  9. catécholamines
  10. cyclisme



Nicholas Preobrazenski
School of Kinesiology and Health Studies, Queen’s University, 28 Division Street, Kingston, ON K7L 3N6, Canada.
Hashim Islam
School of Kinesiology and Health Studies, Queen’s University, 28 Division Street, Kingston, ON K7L 3N6, Canada.
Patrick J. Drouin
School of Kinesiology and Health Studies, Queen’s University, 28 Division Street, Kingston, ON K7L 3N6, Canada.
Jacob T. Bonafiglia
School of Kinesiology and Health Studies, Queen’s University, 28 Division Street, Kingston, ON K7L 3N6, Canada.
Michael E. Tschakovsky
School of Kinesiology and Health Studies, Queen’s University, 28 Division Street, Kingston, ON K7L 3N6, Canada.
Brendon J. Gurd [email protected]
School of Kinesiology and Health Studies, Queen’s University, 28 Division Street, Kingston, ON K7L 3N6, Canada.


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