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

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: <i>p</i> = 0.01; HHb: <i>p</i> < 0.01) and no difference in muscle activation (<i>p</i> = 0.53). Plasma epinephrine increased following both BFR and CTL (<i>p</i> < 0.01); however, only norepinephrine increased more following BFR (<i>p</i> < 0.01). <i>PGC-1α</i> messenger RNA (mRNA) increased more following BFR (∼6-fold) compared with CTL (∼4-fold; <i>p</i> = 0.036). <i>VEGFA</i> mRNA increased (<i>p</i> < 0.01) similarly following BFR and CTL (<i>p</i> = 0.21), and <i>HIF-1α</i> mRNA did not increase following either condition (<i>p</i> = 0.21). Phosphorylated acetyl-coenzyme A carboxylase (ACC) increased more following BFR (<i>p</i> < 0.035) whereas p-PKA substrates, p-p38 MAPK, and acetyl-p53 increased (<i>p</i> < 0.05) similarly following both conditions (<i>p</i> > 0.05). In conclusion, gravity-induced BFR is a viable BFR model that demonstrated an important role of AMPK signalling on augmenting <i>PGC-1α</i> mRNA. <b>Novelty</b> 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 <i>PGC-1α</i> 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.