Buch 2020 FASEB J

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Buch BT, Halling JF, Ringholm S, Gudiksen A, Kjøbsted R, Olsen MA, Wojtaszewski JFP, Pilegaard H (2020) Colchicine treatment impairs skeletal muscle mitochondrial function and insulin sensitivity in an age-specific manner. FASEB J 34:8653-70.

» PMID: 32372536 Open Access

Buch BT, Halling JF, Ringholm S, Gudiksen A, Kjoebsted R, Olsen MA, Wojtaszewski JFP, Pilegaard H (2020) FASEB J

Abstract: The aim of the study was to investigate the impact of autophagy inhibitioin 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.

© 2020 Federation of American Societies for Experimental Biology.

Keywords: ADP sensitivity, ROS, Aging, Autophagy Bioblast editor: Plangger M O2k-Network Lab: DK Copenhagen Pilegaard H


Labels: MiParea: Respiration, Genetic knockout;overexpression  Pathology: Aging;senescence 

Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 


Coupling state: LEAK, OXPHOS  Pathway: N, NS  HRR: Oxygraph-2k, O2k-Fluorometer 

2020-05, AmR