Muscle weakness precedes atrophy during cancer cachexia and is linked to muscle-specific mitochondrial stress.

Autor:	Delfinis LJ; Muscle Health Research Centre, School of Kinesiology, Faculty of Health, York University, Toronto, Ontario, Canada., Bellissimo CA; Muscle Health Research Centre, School of Kinesiology, Faculty of Health, York University, Toronto, Ontario, Canada., Gandhi S; Muscle Health Research Centre, School of Kinesiology, Faculty of Health, York University, Toronto, Ontario, Canada., DiBenedetto SN; Muscle Health Research Centre, School of Kinesiology, Faculty of Health, York University, Toronto, Ontario, Canada., Garibotti MC; Muscle Health Research Centre, School of Kinesiology, Faculty of Health, York University, Toronto, Ontario, Canada., Thuhan AK; Muscle Health Research Centre, School of Kinesiology, Faculty of Health, York University, Toronto, Ontario, Canada., Tsitkanou S; Cachexia Research Laboratory, Department of Health, Human Performance and Recreation, College of Education and Health Professions, University of Arkansas, Fayetteville, Arkansas, USA., Rosa-Caldwell ME; Cachexia Research Laboratory, Department of Health, Human Performance and Recreation, College of Education and Health Professions, University of Arkansas, Fayetteville, Arkansas, USA., Rahman FA; Department of Kinesiology and Health Sciences, Faculty of Health, University of Waterloo, Waterloo, Ontario, Canada., Cheng AJ; Muscle Health Research Centre, School of Kinesiology, Faculty of Health, York University, Toronto, Ontario, Canada., Wiggs MP; Mooney Lab for Exercise, Nutrition, and Biochemistry, Department of Health, Human Performance, and Recreation, Baylor University, Waco, Texas, USA., Schlattner U; Laboratory of Fundamental and Applied Bioenergetics, University Grenoble Alpes and INSERM U1055, Grenoble, France, and Institut Universitaire de France, Paris, France., Quadrilatero J; Department of Kinesiology and Health Sciences, Faculty of Health, University of Waterloo, Waterloo, Ontario, Canada., Greene NP; Cachexia Research Laboratory, Department of Health, Human Performance and Recreation, College of Education and Health Professions, University of Arkansas, Fayetteville, Arkansas, USA., Perry CG; Muscle Health Research Centre, School of Kinesiology, Faculty of Health, York University, Toronto, Ontario, Canada.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2022 Dec 22; Vol. 7 (24). Date of Electronic Publication: 2022 Dec 22.
DOI:	10.1172/jci.insight.155147
Abstrakt:	Muscle weakness and wasting are defining features of cancer-induced cachexia. Mitochondrial stress occurs before atrophy in certain muscles, but the possibility of heterogeneous responses between muscles and across time remains unclear. Using mice inoculated with Colon-26 cancer, we demonstrate that specific force production was reduced in quadriceps and diaphragm at 2 weeks in the absence of atrophy. At this time, pyruvate-supported mitochondrial respiration was lower in quadriceps while mitochondrial H2O2 emission was elevated in diaphragm. By 4 weeks, atrophy occurred in both muscles, but specific force production increased to control levels in quadriceps such that reductions in absolute force were due entirely to atrophy. Specific force production remained reduced in diaphragm. Mitochondrial respiration increased and H2O2 emission was unchanged in both muscles versus control while mitochondrial creatine sensitivity was reduced in quadriceps. These findings indicate muscle weakness precedes atrophy and is linked to heterogeneous mitochondrial alterations that could involve adaptive responses to metabolic stress. Eventual muscle-specific restorations in specific force and bioenergetics highlight how the effects of cancer on one muscle do not predict the response in another muscle. Exploring heterogeneous responses of muscle to cancer may reveal new mechanisms underlying distinct sensitivities, or resistance, to cancer cachexia.
Databáze:	MEDLINE
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