Muscle weakness precedes atrophy during cancer cachexia and is associated with muscle-specific mitochondrial stress

BioRxiv : the Preprint Server for Biology
L. J. DelfinisChristopher G R Perry


Muscle weakness and wasting are defining features of cancer-induced cachexia. Mitochondrial stress occurs before atrophy in certain muscles, but distinct responses between muscles and across time remains unclear. We aimed to determine the time-dependent and muscle-specific responses to Colon-26 (C26) cancer-induced cachexia in mice. At 2 weeks post-inoculation, the presence of small tumours did not alter body or muscle mass but decreased force production in the quadriceps and diaphragm. Pyruvate-supported mitochondrial respiration was lower in quadriceps while mitochondrial H2O2 emission was elevated in diaphragm. At 4 weeks, large tumours corresponded to lower body mass, muscle mass, and cross-sectional area of fibers in quadriceps and diaphragm. Force production in quadriceps was unchanged but remained lower in diaphragm vs control. Mitochondrial respiration was increased while H2O2 emission was unchanged in both muscles vs control. Mitochondrial creatine sensitivity was compromised in quadriceps. These findings indicate muscle weakness precedes atrophy in quadriceps and diaphragm but is linked to heterogeneous mitochondrial alterations. Eventual muscle-specific restorations in force and bioenergetics highlight how the effect...Continue Reading

Methods Mentioned

force measurements

Software Mentioned

GraphPad Prism

Related Concepts

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

Related Papers

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
B M RobertsA R Judge
Biochemical and Biophysical Research Communications
B M RobertsA R Judge
Current Opinion in Clinical Nutrition and Metabolic Care
Rui VitorinoRita Ferreira
Rheumatology and Rehabilitation
M A ChamberlainG Johnson
© 2021 Meta ULC. All rights reserved