Colchicine treatment impairs skeletal muscle mitochondrial function and insulin sensitivity in an age-specific manner

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Standard

Colchicine treatment impairs skeletal muscle mitochondrial function and insulin sensitivity in an age-specific manner. / Buch, Bjørg Thiellesen; Halling, Jens Frey; Ringholm, Stine; Gudiksen, Anders; Kjøbsted, Rasmus; Olsen, Mette Algot; Wojtaszewski, Jørgen; Pilegaard, Henriette.

I: F A S E B Journal, Bind 34, Nr. 6, 2020, s. 8653-8670.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Buch, BT, Halling, JF, Ringholm, S, Gudiksen, A, Kjøbsted, R, Olsen, MA, Wojtaszewski, J & Pilegaard, H 2020, 'Colchicine treatment impairs skeletal muscle mitochondrial function and insulin sensitivity in an age-specific manner', F A S E B Journal, bind 34, nr. 6, s. 8653-8670. https://doi.org/10.1096/fj.201903113RR

APA

Buch, B. T., Halling, J. F., Ringholm, S., Gudiksen, A., Kjøbsted, R., Olsen, M. A., ... Pilegaard, H. (2020). Colchicine treatment impairs skeletal muscle mitochondrial function and insulin sensitivity in an age-specific manner. F A S E B Journal, 34(6), 8653-8670. https://doi.org/10.1096/fj.201903113RR

Vancouver

Buch BT, Halling JF, Ringholm S, Gudiksen A, Kjøbsted R, Olsen MA o.a. Colchicine treatment impairs skeletal muscle mitochondrial function and insulin sensitivity in an age-specific manner. F A S E B Journal. 2020;34(6):8653-8670. https://doi.org/10.1096/fj.201903113RR

Author

Buch, Bjørg Thiellesen ; Halling, Jens Frey ; Ringholm, Stine ; Gudiksen, Anders ; Kjøbsted, Rasmus ; Olsen, Mette Algot ; Wojtaszewski, Jørgen ; Pilegaard, Henriette. / Colchicine treatment impairs skeletal muscle mitochondrial function and insulin sensitivity in an age-specific manner. I: F A S E B Journal. 2020 ; Bind 34, Nr. 6. s. 8653-8670.

Bibtex

@article{f4561186e1e640f98ddab2e0e10249d7,
title = "Colchicine treatment impairs skeletal muscle mitochondrial function and insulin sensitivity in an age-specific manner",
abstract = "The aim of the study was to investigate the impact of autophagy inhibition on skeletal muscle mitochondrial function and glucose homeostasis in young and aged mice. The transcriptional co-activator PGC-1α regulates muscle oxidative phenotype which has been shown to be linked with basal autophagic capacity. Therefore, young and aged inducible muscle-specific PGC-1α knockout (iMKO) mice and littermate lox/lox controls were used in three separate experiments performed after either saline or colchicine injections on two consecutive days: (1) Euthanization in the basal state obtaining skeletal muscle for mitochondrial respirometry, (2) whole body glucose tolerance test, and (3) in vivo insulin-stimulated 2-deoxyglucose (2-DG) uptake into skeletal muscle. Muscle PGC-1α was not required for maintaining basal autophagy flux, regardless of age. Colchicine-induced inhibition of autophagy was associated with impairments of skeletal muscle mitochondrial function, including reduced ADP sensitivity and altered mitochondrial redox balance in both young and aged mice. Colchicine treatment reduced the glucose tolerance in aged, but not young mice, and similarly in iMKO and lox/lox mice. Colchicine reduced insulin-stimulated 2-DG uptake in soleus muscle in aged mice, independently of PGC-1α, and without affecting insulin-regulated phosphorylation of proximal or distal mediators of insulin signaling. In conclusion, the results indicate that autophagy regulates the mitochondrial ADP sensitivity and redox balance as well as whole body glucose tolerance and skeletal muscle insulin sensitivity in aged mice, with no additional effects of inducible PGC-1α deletion.",
keywords = "Faculty of Science, ADP sensitivity, Aging, Autophagy, ROS",
author = "Buch, {Bj{\o}rg Thiellesen} and Halling, {Jens Frey} and Stine Ringholm and Anders Gudiksen and Rasmus Kj{\o}bsted and Olsen, {Mette Algot} and J{\o}rgen Wojtaszewski and Henriette Pilegaard",
note = "{\circledC} 2020 Federation of American Societies for Experimental Biology.",
year = "2020",
doi = "10.1096/fj.201903113RR",
language = "English",
volume = "34",
pages = "8653--8670",
journal = "F A S E B Journal",
issn = "0892-6638",
publisher = "Federation of American Societies for Experimental Biology",
number = "6",

}

RIS

TY - JOUR

T1 - Colchicine treatment impairs skeletal muscle mitochondrial function and insulin sensitivity in an age-specific manner

AU - Buch, Bjørg Thiellesen

AU - Halling, Jens Frey

AU - Ringholm, Stine

AU - Gudiksen, Anders

AU - Kjøbsted, Rasmus

AU - Olsen, Mette Algot

AU - Wojtaszewski, Jørgen

AU - Pilegaard, Henriette

N1 - © 2020 Federation of American Societies for Experimental Biology.

PY - 2020

Y1 - 2020

N2 - The aim of the study was to investigate the impact of autophagy inhibition on skeletal muscle mitochondrial function and glucose homeostasis in young and aged mice. The transcriptional co-activator PGC-1α regulates muscle oxidative phenotype which has been shown to be linked with basal autophagic capacity. Therefore, young and aged inducible muscle-specific PGC-1α knockout (iMKO) mice and littermate lox/lox controls were used in three separate experiments performed after either saline or colchicine injections on two consecutive days: (1) Euthanization in the basal state obtaining skeletal muscle for mitochondrial respirometry, (2) whole body glucose tolerance test, and (3) in vivo insulin-stimulated 2-deoxyglucose (2-DG) uptake into skeletal muscle. Muscle PGC-1α was not required for maintaining basal autophagy flux, regardless of age. Colchicine-induced inhibition of autophagy was associated with impairments of skeletal muscle mitochondrial function, including reduced ADP sensitivity and altered mitochondrial redox balance in both young and aged mice. Colchicine treatment reduced the glucose tolerance in aged, but not young mice, and similarly in iMKO and lox/lox mice. Colchicine reduced insulin-stimulated 2-DG uptake in soleus muscle in aged mice, independently of PGC-1α, and without affecting insulin-regulated phosphorylation of proximal or distal mediators of insulin signaling. In conclusion, the results indicate that autophagy regulates the mitochondrial ADP sensitivity and redox balance as well as whole body glucose tolerance and skeletal muscle insulin sensitivity in aged mice, with no additional effects of inducible PGC-1α deletion.

AB - The aim of the study was to investigate the impact of autophagy inhibition on skeletal muscle mitochondrial function and glucose homeostasis in young and aged mice. The transcriptional co-activator PGC-1α regulates muscle oxidative phenotype which has been shown to be linked with basal autophagic capacity. Therefore, young and aged inducible muscle-specific PGC-1α knockout (iMKO) mice and littermate lox/lox controls were used in three separate experiments performed after either saline or colchicine injections on two consecutive days: (1) Euthanization in the basal state obtaining skeletal muscle for mitochondrial respirometry, (2) whole body glucose tolerance test, and (3) in vivo insulin-stimulated 2-deoxyglucose (2-DG) uptake into skeletal muscle. Muscle PGC-1α was not required for maintaining basal autophagy flux, regardless of age. Colchicine-induced inhibition of autophagy was associated with impairments of skeletal muscle mitochondrial function, including reduced ADP sensitivity and altered mitochondrial redox balance in both young and aged mice. Colchicine treatment reduced the glucose tolerance in aged, but not young mice, and similarly in iMKO and lox/lox mice. Colchicine reduced insulin-stimulated 2-DG uptake in soleus muscle in aged mice, independently of PGC-1α, and without affecting insulin-regulated phosphorylation of proximal or distal mediators of insulin signaling. In conclusion, the results indicate that autophagy regulates the mitochondrial ADP sensitivity and redox balance as well as whole body glucose tolerance and skeletal muscle insulin sensitivity in aged mice, with no additional effects of inducible PGC-1α deletion.

KW - Faculty of Science

KW - ADP sensitivity

KW - Aging

KW - Autophagy

KW - ROS

U2 - 10.1096/fj.201903113RR

DO - 10.1096/fj.201903113RR

M3 - Journal article

C2 - 32372536

VL - 34

SP - 8653

EP - 8670

JO - F A S E B Journal

JF - F A S E B Journal

SN - 0892-6638

IS - 6

ER -

ID: 241044181