Attenuated PGC-1α Isoforms following Endurance Exercise with Blood Flow Restriction

Conceição, Miguel Soares; Chacon-Mikahil, Mara Patrícia Traina; Telles, Guilherme Defante; Libardi, Cleiton Augusto; Mendes, Edson Manoel; Vechin, Felipe Cassaro; Andrade, André; Gáspari, Arthur Fernandes; Brum, Patrícia Chakur; Cavaglieri, Cláudia Regina; Serag, Sara; Spiegelman, Bruce M.; Hawley, John A.; Camera, Donny M.

doi:10.1249/mss.0000000000000970

Cited by 29 publications

(32 citation statements)

References 38 publications

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“…51. The exercise protocol comprise a standardized warm-up period following by 30-min of cycling, at 70% of VO 2peak .…”

Section: Methodsmentioning

confidence: 99%

“…The animal experiments were conducted following to the last revision of the National Institutes of Health (NIH) guide for the care and use of laboratory animals. In the case of humans, the experimental procedures were explained to all subjects, who provided written informed consent before the study that was conducted according to the latest revision of the Declaration of Helsinki51.…”

Section: Methodsmentioning

confidence: 99%

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Interleukin-6 increases the expression and activity of insulin-degrading enzyme

Kurauti

Costa-Júnior

Ferreira

et al. 2017

Sci Rep

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Impairment of the insulin-degrading enzyme (IDE) is associated with obesity and type 2 diabetes mellitus (T2DM). Here, we used 4-mo-old male C57BL/6 interleukin-6 (IL-6) knockout mice (KO) to investigate the role of this cytokine on IDE expression and activity. IL-6 KO mice displayed lower insulin clearance in the liver and skeletal muscle, compared with wild type (WT), due to reduced IDE expression and activity. We also observed that after 3-h incubation, IL-6, 50 and 100 ng ml−1, increased the expression of IDE in HEPG2 and C2C12 cells, respectively. In addition, during acute exercise, the inhibition of IL-6 prevented an increase in insulin clearance and IDE expression and activity, mainly in the skeletal muscle. Finally, IL-6 and IDE concentrations were significantly increased in plasma from humans, after an acute exercise, compared to pre-exercise values. Although the increase in plasma IDE activity was only marginal, a positive correlation between IL-6 and IDE activity, and between IL-6 and IDE protein expression, was observed. Our outcomes indicate a novel function of IL-6 on the insulin metabolism expanding the possibilities for new potential therapeutic strategies, focused on insulin degradation, for the treatment and/or prevention of diseases related to hyperinsulinemia, such as obesity and T2DM.

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“…51. The exercise protocol comprise a standardized warm-up period following by 30-min of cycling, at 70% of VO 2peak .…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Interleukin-6 increases the expression and activity of insulin-degrading enzyme

Kurauti

Costa-Júnior

Ferreira

et al. 2017

Sci Rep

View full text Add to dashboard Cite

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“…Given these isoforms likely exert different functions in skeletal muscle and are regulated at the mRNA level by muscle activity, this would seem of great physiological relevance. Furthermore, although 3 studies have assessed the effects of BFR on exercise‐induced changes in PGC‐1α mRNA content in human muscle, only one study measured different PGC‐1α transcripts . In these studies, BFR either attenuated, augmented, or had no effect on changes in PGC‐1α mRNA content after exercise.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, although 3 studies have assessed the effects of BFR on exercise‐induced changes in PGC‐1α mRNA content in human muscle, only one study measured different PGC‐1α transcripts . In these studies, BFR either attenuated, augmented, or had no effect on changes in PGC‐1α mRNA content after exercise. These contradictory findings are likely related to the different experimental approaches used (eg type and intensity of exercise and the timing of BFR).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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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.

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“…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 . In an alternative approach, the study by Taylor et al specifically chose sprint interval training with post‐exercise BFR to ensure that a high training intensity was maintained, which is in line with current training theory .…”

mentioning

confidence: 99%

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

Ferguson

2018

Acta Physiologica

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. 2018. Increased FXYD1 and PGC-1a mRNA after blood flowrestricted running is related to fibre typespecific AMPK signalling and oxidative stress in human muscle. Acta Physiol 223, e13045.Blood flow restriction (BFR) has been utilized in physiology for centuries, from William Harvey's (1578-1657) initial use of a tourniquet to describe in detail the systemic circulation of blood, to the use in the last 40 years in the investigation of cardiovascular reflex responses, angiogenesis, skeletal muscle metabolism and fatigue. Recent investigation has largely focussed on the adaptive potential of BFR exercise training, with particular reference to skeletal muscle strength and hypertrophy and its use in the rehabilitation process. 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 1 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. In their study, recreational athletes (with a reasonable VO 2max of~57 mL min À1 kg À1 ) completed interval sessions consisting of three sets of three 2-minute running bouts. In an interesting experimental design, these were performed alone, with BFR and under normobaric hypoxic conditions (F I O 2 of 14%). By ensuring the level of skeletal muscle hypoxia (deoxygenation measured by NIRS) was consistent between the BFR and hypoxic conditions the investigators were able to ascertain whether hypoxia per se was involved in the adaptive process (as might be have been expected with the use of BFR). The exciting and novel observations were that BFR augmented the increase in mRNA expression of the Na + ,K + -ATPase (NKA) complex ancillary protein phospholemman-1 (FXYD1), which contributes to the maintenance of transmembrane Na + and K + ion gradients, critical in preserving skeletal muscle membrane excitability and thus contractile function. 2 They also demonstrated that BFR augmented the expression of specific isoforms of peroxisome proliferator-activated receptor-c coactivator 1a (PGC-1a), which is widely considered to be the key factor mediating exercise training-induced adaptations in mitochondrial capacity. 3 Interestingly, the augmented upregulation of these transcripts was unrelated to the severity of muscle hypoxia, lactate accumulation and activation of Ca 2+ /calmodulindependent protein kinase (CaMKII). Instead, the key physiological signals were related to the level of oxidative stress and fibre type specific 5 0 AMP-activated protein kinase (AMPK) signalling. This study clearly improves our understanding of the physiological stressors involved in the regulation of NKA and PGC-1a expression, and how these stressors can be influenced by BFR. The study also adds support to the debate on the potent...

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Attenuated PGC-1α Isoforms following Endurance Exercise with Blood Flow Restriction

Cited by 29 publications

References 38 publications

Interleukin-6 increases the expression and activity of insulin-degrading enzyme

Interleukin-6 increases the expression and activity of insulin-degrading enzyme

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

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

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