Skeletal Muscle Mitochondrial Protein Synthesis and Respiration Increase With Low-Load Blood Flow Restricted as Well as High-Load Resistance Training

TY - JOUR

T1 - Skeletal Muscle Mitochondrial Protein Synthesis and Respiration Increase With Low-Load Blood Flow Restricted as Well as High-Load Resistance Training

AU - Grønnebæk, Thomas Skjærlund

AU - Jespersen, Nichlas Riise

AU - Jakobsgaard, Jesper Emil

AU - Sieljacks, Peter

AU - Wang, Jakob

AU - Rindom, Emil

AU - Musci, Robert V.

AU - Bøtker, Hans Erik

AU - Hamilton, Karyn L.

AU - Miller, Benjamin F.

AU - de Paoli, Frank Vincenzo

AU - Vissing, Kristian

PY - 2018/12/17

Y1 - 2018/12/17

N2 - Purpose: It is well established that high-load resistance exercise (HLRE) can stimulate myofibrillar accretion. Additionally, recent studies suggest that HLRE can also stimulate mitochondrial biogenesis and respiratory function. However, in several clinical situations, the use of resistance exercise with high loading may not constitute a viable approach. Low-load blood flow restricted resistance exercise (BFRRE) has emerged as a timeeffective low-load alternative to stimulate myofibrillar accretion. It is unknown if BFRRE can also stimulate mitochondrial biogenesis and respiratory function. If so, BFRRE could provide a feasible strategy to stimulate muscle metabolic health. Methods: To study this, 34 healthy previously untrained individuals (24 ± 3 years) participated in BFRRE, HLRE, or non-exercise control intervention (CON) 3 times per week for 6 weeks. Skeletal muscle biopsies were collected; (1) before and after the 6-week intervention period to assess mitochondrial biogenesis and respiratory function and; (2) during recovery from single-bout exercise to assess myocellular signaling events involved in transcriptional regulation of mitochondrial biogenesis. During the 6-week intervention period, deuterium oxide (D 2O) was continuously administered to the participants to label newly synthesized skeletal muscle mitochondrial proteins. Mitochondrial respiratory function was assessed in permeabilized muscle fibers with high-resolution respirometry. Mitochondrial content was assessed with a citrate synthase activity assay. Myocellular signaling was assessed with immunoblotting. Results: Mitochondrial protein synthesis rate was higher with BFRRE (1.19%/day) and HLRE (1.15%/day) compared to CON (0.92%/day) (P < 0.05) but similar between exercise groups. Mitochondrial respiratory function increased to similar degree with both exercise regimens and did not change with CON. For instance, coupled respiration supported by convergent electron flow from complex I and II increased 38% with BFRRE and 24% with HLRE (P < 0.01). Training did not alter citrate synthase activity compared to CON. BFRRE and HLRE elicited similar myocellular signaling responses. Conclusion: These results support recent findings that resistance exercise stimulate mitochondrial biogenesis and respiratory function to support healthy skelmuscle and whole-body metabolism. Intriquingly, BFRRE produces similar mitochondadaptations at a markedly lower load, which entail great clinical perspective populations in whom exercise with high loading is untenable.

AB - Purpose: It is well established that high-load resistance exercise (HLRE) can stimulate myofibrillar accretion. Additionally, recent studies suggest that HLRE can also stimulate mitochondrial biogenesis and respiratory function. However, in several clinical situations, the use of resistance exercise with high loading may not constitute a viable approach. Low-load blood flow restricted resistance exercise (BFRRE) has emerged as a timeeffective low-load alternative to stimulate myofibrillar accretion. It is unknown if BFRRE can also stimulate mitochondrial biogenesis and respiratory function. If so, BFRRE could provide a feasible strategy to stimulate muscle metabolic health. Methods: To study this, 34 healthy previously untrained individuals (24 ± 3 years) participated in BFRRE, HLRE, or non-exercise control intervention (CON) 3 times per week for 6 weeks. Skeletal muscle biopsies were collected; (1) before and after the 6-week intervention period to assess mitochondrial biogenesis and respiratory function and; (2) during recovery from single-bout exercise to assess myocellular signaling events involved in transcriptional regulation of mitochondrial biogenesis. During the 6-week intervention period, deuterium oxide (D 2O) was continuously administered to the participants to label newly synthesized skeletal muscle mitochondrial proteins. Mitochondrial respiratory function was assessed in permeabilized muscle fibers with high-resolution respirometry. Mitochondrial content was assessed with a citrate synthase activity assay. Myocellular signaling was assessed with immunoblotting. Results: Mitochondrial protein synthesis rate was higher with BFRRE (1.19%/day) and HLRE (1.15%/day) compared to CON (0.92%/day) (P < 0.05) but similar between exercise groups. Mitochondrial respiratory function increased to similar degree with both exercise regimens and did not change with CON. For instance, coupled respiration supported by convergent electron flow from complex I and II increased 38% with BFRRE and 24% with HLRE (P < 0.01). Training did not alter citrate synthase activity compared to CON. BFRRE and HLRE elicited similar myocellular signaling responses. Conclusion: These results support recent findings that resistance exercise stimulate mitochondrial biogenesis and respiratory function to support healthy skelmuscle and whole-body metabolism. Intriquingly, BFRRE produces similar mitochondadaptations at a markedly lower load, which entail great clinical perspective populations in whom exercise with high loading is untenable.

KW - bioenergetics

KW - deuterium oxide

KW - high-resolution respirometry

KW - ischemic resistance training

KW - mitochondrial biogenesis

UR - http://www.scopus.com/inward/record.url?scp=85068265201&partnerID=8YFLogxK

U2 - 10.3389/fphys.2018.01796

DO - 10.3389/fphys.2018.01796

M3 - Journal article

C2 - 30618808

SN - 1664-042X

VL - 9

JO - Frontiers in Physiology

JF - Frontiers in Physiology

M1 - 1796

ER -