Increased FXYD1 and PGC‐1α mRNA after blood flow‐restricted running is related to fibre type‐specific AMPK signalling and oxidative stress in human muscle

Abstract

AimThis study explored the effects of blood flow restriction (BFR) on mRNA responses of PGC‐1α (total, 1α1, and 1α4) and Na+,K+‐ATPase isoforms (NKA; α1‐3, β1‐3, and FXYD1) to an interval running session and determined whether these effects were related to increased oxidative stress, hypoxia, and fibre type‐specific AMPK and CaMKII signalling, in human skeletal muscle.MethodsIn a randomized, crossover fashion, 8 healthy men (26 ± 5 year and 57.4 ± 6.3 mL kg−1 min−1) completed 3 exercise sessions: without (CON) or with blood flow restriction (BFR), or in systemic hypoxia (HYP, ~3250 m). A muscle sample was collected before (Pre) and after exercise (+0 hour, +3 hours) to quantify mRNA, indicators of oxidative stress (HSP27 protein in type I and II fibres, and catalase and HSP70 mRNA), metabolites, and α‐AMPK Thr172/α‐AMPK, ACC Ser221/ACC, CaMKII Thr287/CaMKII, and PLBSer16/PLB ratios in type I and II fibres.ResultsMuscle hypoxia (assessed by near‐infrared spectroscopy) was matched between BFR and HYP, which was higher than CON (~90% vs ~70%; P < .05). The mRNA levels of FXYD1 and PGC‐1α isoforms (1α1 and 1α4) increased in BFR only (P < .05) and were associated with increases in indicators of oxidative stress and type I fibre ACC Ser221/ACC ratio, but dissociated from muscle hypoxia, lactate, and CaMKII signalling.ConclusionBlood flow restriction augmented exercise‐induced increases in muscle FXYD1 and PGC‐1α mRNA in men. This effect was related to increased oxidative stress and fibre type‐dependent AMPK signalling, but unrelated to the severity of muscle hypoxia, lactate accumulation, and modulation of fibre type‐specific CaMKII signalling.

Metabolic stress‐dependent regulation of the mitochondrial biogenic molecular response to high‐intensity exercise in human skeletal muscle

“…Further evidence supporting the sensitivity of muscle PGC‐1α transcription to the metabolic environment has been provided by studies using either blood flow‐restricted exercise (Norrbom et al . 2004; Christiansen et al . 2018), nutritional means (Edge et al .…”

Blood flow‐restricted exercise: Providing more bang for buck in trained athletes?

“…Others have continued to explore the potential for BFR in enhancing the skeletal muscle signalling response and subsequent improvement to whole body exercise performance. Adding to this latter aspect, the paper by Christiansen et al in this issue of Acta Physiologica provides further convincing evidence on the potential for BFR exercise to augment skeletal muscle signalling responses, particularly related to the physiological mechanisms associated with fatigue resistance and mitochondrial capacity.…”

“…As a consequence, there would be a greater available capacity for further gene transcription. Indeed, Christiansen et al demonstrated that BFR augmented PGC‐1α mRNA transcription up to 4.3‐fold. This is compared to the other studies that have investigated the effects of BFR on PGC‐1α expression, in which there was either no effect or an attenuated response .…”

“…What makes the study by Christiansen et al particularly timely is the general thought that phenotypic adaptations to exercise training are more difficult to elicit in well‐trained athletes who already possess the necessary physiology to be competitive in their chosen event. Early research has highlighted the reduced plasticity of skeletal muscle in the trained state .…”

“…Moreover, this blunting of the adaptive scope in trained individuals, or in response to exercise training, is reflected at a molecular level . The “trained” status of participants in studies by Christiansen et al (VO 2max of ~57 mL min −1 kg −1 ) and Taylor et al (VO 2max of ~60 mL min −1 kg −1 ) suggest that, regardless of exercise intensity or modality, BFR may overcome the blunted nature of the acute signalling response to exercise and act as a potent stimulus in enhancing a broad range of adaptive processes. Clearly, however, long‐term training studies are required to confirm whether these augmented signals translate into phenotypic changes.…”