Molecular regulation of skeletal muscle mitochondrial biogenesis following blood flow-restricted aerobic exercise: a call to action.

Blood flow-restricted (BFR) exercise can induce training adaptations comparable to those observed following training in free flow conditions. However, little is known about the acute responses within skeletal muscle following BFR aerobic exercise (AE). Moreover, although preliminary evidence suggests chronic BFR AE may augment certain training adaptations in skeletal muscle mitochondria more than non-BFR AE, the underlying mechanisms are poorly understood. In this review, we summarise the acute BFR AE literature examining mitochondrial biogenic signalling pathways and provide insight into mechanisms linked to skeletal muscle remodelling following BFR AE. Specifically, we focus on signalling pathways potentially contributing to augmented peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) mRNA following work-rate-matched BFR AE compared with non-BFR AE. We present evidence suggesting reductions in muscle oxygenation during acute BFR AE lead to increased intracellular energetic stress, AMP-activated protein kinase (AMPK) activation and PGC-1α mRNA. In addition, we briefly discuss mitochondrial adaptations to BFR aerobic training, and we assess the risk of bias using the Cochrane Collaboration risk of bias assessment tool. We ultimately call for several straightforward modifications to help minimise bias in future BFR AE studies.