Exercise increases phosphorylation of the putative mTORC2 activity readout NDRG1 in human skeletal muscle

Research output: Contribution to journalJournal articlepeer-review

Standard

Exercise increases phosphorylation of the putative mTORC2 activity readout NDRG1 in human skeletal muscle. / Knudsen, Jonas Roland; Persson, Kaspar Wredstrøm; Meister, Jaroslawna; Carl, Christian Strini; Raun, Steffen Henning; Andersen, Nicoline Resen; Sylow, Lykke; Kiens, Bente; Jensen, Thomas Elbenhardt; Richter, Erik A.; Kleinert, Maximilian.

In: American Journal of Physiology: Endocrinology and Metabolism, Vol. 322, No. 1, 2022, p. E63-E73.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Knudsen, JR, Persson, KW, Meister, J, Carl, CS, Raun, SH, Andersen, NR, Sylow, L, Kiens, B, Jensen, TE, Richter, EA & Kleinert, M 2022, 'Exercise increases phosphorylation of the putative mTORC2 activity readout NDRG1 in human skeletal muscle', American Journal of Physiology: Endocrinology and Metabolism, vol. 322, no. 1, pp. E63-E73. https://doi.org/10.1152/ajpendo.00389.2021

APA

Knudsen, J. R., Persson, K. W., Meister, J., Carl, C. S., Raun, S. H., Andersen, N. R., Sylow, L., Kiens, B., Jensen, T. E., Richter, E. A., & Kleinert, M. (2022). Exercise increases phosphorylation of the putative mTORC2 activity readout NDRG1 in human skeletal muscle. American Journal of Physiology: Endocrinology and Metabolism, 322(1), E63-E73. https://doi.org/10.1152/ajpendo.00389.2021

Vancouver

Knudsen JR, Persson KW, Meister J, Carl CS, Raun SH, Andersen NR et al. Exercise increases phosphorylation of the putative mTORC2 activity readout NDRG1 in human skeletal muscle. American Journal of Physiology: Endocrinology and Metabolism. 2022;322(1):E63-E73. https://doi.org/10.1152/ajpendo.00389.2021

Author

Knudsen, Jonas Roland ; Persson, Kaspar Wredstrøm ; Meister, Jaroslawna ; Carl, Christian Strini ; Raun, Steffen Henning ; Andersen, Nicoline Resen ; Sylow, Lykke ; Kiens, Bente ; Jensen, Thomas Elbenhardt ; Richter, Erik A. ; Kleinert, Maximilian. / Exercise increases phosphorylation of the putative mTORC2 activity readout NDRG1 in human skeletal muscle. In: American Journal of Physiology: Endocrinology and Metabolism. 2022 ; Vol. 322, No. 1. pp. E63-E73.

Bibtex

@article{9fe94f7110704f6c941ad61eb56d46b7,
title = "Exercise increases phosphorylation of the putative mTORC2 activity readout NDRG1 in human skeletal muscle",
abstract = "In mice, exercise is suggested to activate the mechanistic target of rapamycin complex 2 (mTORC2) in skeletal muscle, and mTORC2 is required for normal muscle glucose uptake during exercise. Whether this translates to human skeletal muscle and what signaling pathways facilitate the exercise-induced mTORC2 activation is unknown but important to determine given the important role of mTORC2 in metabolism. We herein tested the hypothesis that exercise increases mTORC2 activity in human skeletal muscle and investigated if β2-adrenergic receptor (AR) activation mediates exercise-induced mTORC2 activation. We examined several mTORC2 activity readouts (p-NDRG1 Thr346, p-Akt Ser473, p-mTOR S2481, and p-Akt Thr450) in human skeletal muscle biopsies after uphill walking or cycling exercise. In mouse muscles, we assessed mTORC2 activity readouts following acute activation of muscle β2-adrenergic or Gs signaling and during in vivo and ex vivo muscle contractions. Exercise increased phosphorylation of NDRG1 Thr346 in human soleus, gastrocnemius, and vastus lateralis muscle, without changing p-Akt Ser473, p-Akt Thr450, and p-mTOR Ser2481. In mouse muscle, stimulation of β2-adrenergic or Gs signaling and ex vivo contractions failed to increase p-NDRG1 Thr346, while in vivo contractions were sufficient to induce p-NDRG1 Thr346. In conclusion, the mTORC2 activity readout p-NDRG1 Thr346 is a novel exercise-responsive signaling protein in human skeletal muscle. Notably, contraction-induced p-NDRG1 Thr346 appears to require a systemic factor. Unlike exercise, and in contrast to published data obtained in cultured muscles cells, stimulation of β2-adrenergic signaling is not sufficient to trigger NDRG1 phosphorylation in mature mouse skeletal muscle.",
keywords = "Faculty of Science, Exercise, mTORC2, Skeletal muscle, β-adrenergic signaling, Humans",
author = "Knudsen, {Jonas Roland} and Persson, {Kaspar Wredstr{\o}m} and Jaroslawna Meister and Carl, {Christian Strini} and Raun, {Steffen Henning} and Andersen, {Nicoline Resen} and Lykke Sylow and Bente Kiens and Jensen, {Thomas Elbenhardt} and Richter, {Erik A.} and Maximilian Kleinert",
note = "CURIS 2022 NEXS 028",
year = "2022",
doi = "10.1152/ajpendo.00389.2021",
language = "English",
volume = "322",
pages = "E63--E73",
journal = "American Journal of Physiology - Endocrinology and Metabolism",
issn = "0193-1849",
publisher = "American Physiological Society",
number = "1",

}

RIS

TY - JOUR

T1 - Exercise increases phosphorylation of the putative mTORC2 activity readout NDRG1 in human skeletal muscle

AU - Knudsen, Jonas Roland

AU - Persson, Kaspar Wredstrøm

AU - Meister, Jaroslawna

AU - Carl, Christian Strini

AU - Raun, Steffen Henning

AU - Andersen, Nicoline Resen

AU - Sylow, Lykke

AU - Kiens, Bente

AU - Jensen, Thomas Elbenhardt

AU - Richter, Erik A.

AU - Kleinert, Maximilian

N1 - CURIS 2022 NEXS 028

PY - 2022

Y1 - 2022

N2 - In mice, exercise is suggested to activate the mechanistic target of rapamycin complex 2 (mTORC2) in skeletal muscle, and mTORC2 is required for normal muscle glucose uptake during exercise. Whether this translates to human skeletal muscle and what signaling pathways facilitate the exercise-induced mTORC2 activation is unknown but important to determine given the important role of mTORC2 in metabolism. We herein tested the hypothesis that exercise increases mTORC2 activity in human skeletal muscle and investigated if β2-adrenergic receptor (AR) activation mediates exercise-induced mTORC2 activation. We examined several mTORC2 activity readouts (p-NDRG1 Thr346, p-Akt Ser473, p-mTOR S2481, and p-Akt Thr450) in human skeletal muscle biopsies after uphill walking or cycling exercise. In mouse muscles, we assessed mTORC2 activity readouts following acute activation of muscle β2-adrenergic or Gs signaling and during in vivo and ex vivo muscle contractions. Exercise increased phosphorylation of NDRG1 Thr346 in human soleus, gastrocnemius, and vastus lateralis muscle, without changing p-Akt Ser473, p-Akt Thr450, and p-mTOR Ser2481. In mouse muscle, stimulation of β2-adrenergic or Gs signaling and ex vivo contractions failed to increase p-NDRG1 Thr346, while in vivo contractions were sufficient to induce p-NDRG1 Thr346. In conclusion, the mTORC2 activity readout p-NDRG1 Thr346 is a novel exercise-responsive signaling protein in human skeletal muscle. Notably, contraction-induced p-NDRG1 Thr346 appears to require a systemic factor. Unlike exercise, and in contrast to published data obtained in cultured muscles cells, stimulation of β2-adrenergic signaling is not sufficient to trigger NDRG1 phosphorylation in mature mouse skeletal muscle.

AB - In mice, exercise is suggested to activate the mechanistic target of rapamycin complex 2 (mTORC2) in skeletal muscle, and mTORC2 is required for normal muscle glucose uptake during exercise. Whether this translates to human skeletal muscle and what signaling pathways facilitate the exercise-induced mTORC2 activation is unknown but important to determine given the important role of mTORC2 in metabolism. We herein tested the hypothesis that exercise increases mTORC2 activity in human skeletal muscle and investigated if β2-adrenergic receptor (AR) activation mediates exercise-induced mTORC2 activation. We examined several mTORC2 activity readouts (p-NDRG1 Thr346, p-Akt Ser473, p-mTOR S2481, and p-Akt Thr450) in human skeletal muscle biopsies after uphill walking or cycling exercise. In mouse muscles, we assessed mTORC2 activity readouts following acute activation of muscle β2-adrenergic or Gs signaling and during in vivo and ex vivo muscle contractions. Exercise increased phosphorylation of NDRG1 Thr346 in human soleus, gastrocnemius, and vastus lateralis muscle, without changing p-Akt Ser473, p-Akt Thr450, and p-mTOR Ser2481. In mouse muscle, stimulation of β2-adrenergic or Gs signaling and ex vivo contractions failed to increase p-NDRG1 Thr346, while in vivo contractions were sufficient to induce p-NDRG1 Thr346. In conclusion, the mTORC2 activity readout p-NDRG1 Thr346 is a novel exercise-responsive signaling protein in human skeletal muscle. Notably, contraction-induced p-NDRG1 Thr346 appears to require a systemic factor. Unlike exercise, and in contrast to published data obtained in cultured muscles cells, stimulation of β2-adrenergic signaling is not sufficient to trigger NDRG1 phosphorylation in mature mouse skeletal muscle.

KW - Faculty of Science

KW - Exercise

KW - mTORC2

KW - Skeletal muscle

KW - β-adrenergic signaling

KW - Humans

U2 - 10.1152/ajpendo.00389.2021

DO - 10.1152/ajpendo.00389.2021

M3 - Journal article

C2 - 34866401

VL - 322

SP - E63-E73

JO - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

SN - 0193-1849

IS - 1

ER -

ID: 286421701