TY - JOUR
T1 - Recovery of muscle mass and muscle oxidative phenotype following disuse does not require GSK-3 inactivation
AU - Theeuwes, Wessel F.
AU - Pansters, Nicholas A. M.
AU - Gosker, Harry R.
AU - Schols, Annemie M. W. J.
AU - Verhees, Koen J. P.
AU - de Theije, Chiel C.
AU - van Gorp, Rick H. P.
AU - Kelders, Marco C. J. M.
AU - Ronda, Onne
AU - Haegens, Astrid
AU - Remels, Alexander H.
AU - Langen, Ramon C. J.
N1 - Funding Information:
We would like to kindly thank Dr. Niki Ubags (MUMC+, the Netherlands), for her contribution during the animal experimental work. We thank Dr. Sakamoto for providing us with breeding pairs of the C.A. GSK-3 knock-in mice [63]. This work was supported by a grant from the Lung Foundation/Netherlands Asthma Foundation (NAF 3.2.07.017), the Transnational University Limburg (tUL) and ZonMw (114024056).
Funding Information:
We would like to kindly thank Dr. Niki Ubags (MUMC+, the Netherlands), for her contribution during the animal experimental work. We thank Dr. Sakamoto for providing us with breeding pairs of the C.A. GSK-3 knock-in mice [ 63 ]. This work was supported by a grant from the Lung Foundation / Netherlands Asthma Foundation (NAF 3.2.07.017 ), the Transnational University Limburg (tUL) and ZonMw ( 114024056 ).
Publisher Copyright:
© 2020 The Author(s)
PY - 2020/6/1
Y1 - 2020/6/1
N2 - Background: Physical inactivity contributes to muscle wasting and reductions in mitochondrial oxidative phenotype (OXPHEN), reducing physical performance and quality of life during aging and in chronic disease. Previously, it was shown that inactivation of glycogen synthase kinase (GSK)-3 beta stimulates muscle protein accretion, myogenesis, and mitochondrial biogenesis. Additionally, GSK-3 beta is inactivated during recovery of disuse-induced muscle atrophy.Aim: Therefore, we hypothesize that GSK-3 inhibition is required for reloading-induced recovery of skeletal muscle mass and OXPHEN.Methods: Wild-type (WT) and whole-body constitutively active (C.A.) Ser(21/9) GSK-3 alpha/beta knock-in mice were subjected to a 14-day hind-limb suspension/14-day reloading protocol. Soleus muscle mass, fiber cross-sectional area (CSA), OXPHEN (abundance of sub-units of oxidative phosphorylation (OXPHOS) complexes and fiber-type composition), as well as expression levels of their main regulators (respectively protein synthesis/degradation, myogenesis and peroxisome proliferator-activated receptor-gamma co-activator-1 alpha (PGC-1 alpha) signaling) were monitored.Results: Subtle but consistent differences suggesting suppression of protein turnover signaling and decreased expression of several OXPHOS sub-units and PGC-1 alpha signaling constituents were observed at baseline in C.A. GSK-3 versus WT mice. Although soleus mass recovery during reloading occurred more rapidly in C.A. GSK-3 mice, this was not accompanied by a parallel increased CSA. The OXPHEN response to reloading was not distinct between C.A. GSK-3 and WT mice. No consistent or significant differences in reloading-induced changes in the regulatory steps of protein turnover, myogenesis or muscle OXPHEN were observed in C.A. GSK-3 compared to WT muscle.Conclusion: This study indicates that GSK-3 inactivation is dispensable for reloading-induced recovery of muscle mass and OXPHEN.
AB - Background: Physical inactivity contributes to muscle wasting and reductions in mitochondrial oxidative phenotype (OXPHEN), reducing physical performance and quality of life during aging and in chronic disease. Previously, it was shown that inactivation of glycogen synthase kinase (GSK)-3 beta stimulates muscle protein accretion, myogenesis, and mitochondrial biogenesis. Additionally, GSK-3 beta is inactivated during recovery of disuse-induced muscle atrophy.Aim: Therefore, we hypothesize that GSK-3 inhibition is required for reloading-induced recovery of skeletal muscle mass and OXPHEN.Methods: Wild-type (WT) and whole-body constitutively active (C.A.) Ser(21/9) GSK-3 alpha/beta knock-in mice were subjected to a 14-day hind-limb suspension/14-day reloading protocol. Soleus muscle mass, fiber cross-sectional area (CSA), OXPHEN (abundance of sub-units of oxidative phosphorylation (OXPHOS) complexes and fiber-type composition), as well as expression levels of their main regulators (respectively protein synthesis/degradation, myogenesis and peroxisome proliferator-activated receptor-gamma co-activator-1 alpha (PGC-1 alpha) signaling) were monitored.Results: Subtle but consistent differences suggesting suppression of protein turnover signaling and decreased expression of several OXPHOS sub-units and PGC-1 alpha signaling constituents were observed at baseline in C.A. GSK-3 versus WT mice. Although soleus mass recovery during reloading occurred more rapidly in C.A. GSK-3 mice, this was not accompanied by a parallel increased CSA. The OXPHEN response to reloading was not distinct between C.A. GSK-3 and WT mice. No consistent or significant differences in reloading-induced changes in the regulatory steps of protein turnover, myogenesis or muscle OXPHEN were observed in C.A. GSK-3 compared to WT muscle.Conclusion: This study indicates that GSK-3 inactivation is dispensable for reloading-induced recovery of muscle mass and OXPHEN.
KW - GSK-3
KW - Skeletal muscle
KW - Muscle mass
KW - Oxidative phenotype
KW - Unloading/reloading
KW - GLYCOGEN-SYNTHASE KINASE-3-BETA
KW - GROWTH-FACTOR-I
KW - HUMAN SKELETAL-MUSCLE
KW - RAT SOLEUS MUSCLE
KW - SATELLITE CELL
KW - MYOGENIC DIFFERENTIATION
KW - MITOCHONDRIAL BIOGENESIS
KW - INFLAMMATORY RESPONSES
KW - TRANSCRIPTION FACTORS
KW - PROTEIN-DEGRADATION
U2 - 10.1016/j.bbadis.2020.165740
DO - 10.1016/j.bbadis.2020.165740
M3 - Article
C2 - 32087280
SN - 0925-4439
VL - 1866
JO - Biochimica et Biophysica Acta-Molecular Basis of Disease
JF - Biochimica et Biophysica Acta-Molecular Basis of Disease
IS - 6
M1 - 165740
ER -