Difference between revisions of "Delfinis 2022 JCI Insight"

Revision as of 19:22, 17 November 2022

Delfinis LJ, Bellissimo CA, Gandhi S, DiBenedetto SN, Garibotti MC, Thuhan AK, Tsitkanou S, Rosa-Caldwell ME, Rahman FA, Cheng AJ, Wiggs MP, Schlattner U, Quadrilatero J, Greene NP, Perry CG (2022) Muscle weakness precedes atrophy during cancer cachexia and is linked to muscle-specific mitochondrial stress. https://doi.org/10.1172/jci.insight.155147

» JCI Insight [Epub ahead of print]. PMID: 36346680 Open Access

Delfinis LJ, Bellissimo CA, Gandhi S, DiBenedetto SN, Garibotti MC, Thuhan AK, Tsitkanou S, Rosa-Caldwell ME, Rahman FA, Cheng AJ, Wiggs MP, Schlattner U, Quadrilatero J, Greene NP, Perry CG (2022) JCI Insight

Abstract: 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 (C26) 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 vs 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 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. • Keywords: Colorectal cancer, Metabolism, Mitochondria, Oncology, Skeletal muscle • Bioblast editor: Plangger M

Labels: MiParea: Respiration

HRR: Oxygraph-2k

2022-11

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 {{Publication
-|title=Delfinis LJ, Bellissimo CA, Gandhi S, DiBenedetto SN, Garibotti MC, Thuhan AK, Tsitkanou S, Rosa-Caldwell ME, Rahman FA, Cheng AJ, Wiggs MP, Schlattner U, Quadrilatero J, Greene NP, Perry CG (2022) Muscle weakness precedes atrophy during cancer cachexia and is linked to muscle-specific mitochondrial stress.
+|title=Delfinis LJ, Bellissimo CA, Gandhi S, DiBenedetto SN, Garibotti MC, Thuhan AK, Tsitkanou S, Rosa-Caldwell ME, Rahman FA, Cheng AJ, Wiggs MP, Schlattner U, Quadrilatero J, Greene NP, Perry CG (2022) Muscle weakness precedes atrophy during cancer cachexia and is linked to muscle-specific mitochondrial stress. https://doi.org/10.1172/jci.insight.155147
 |info=JCI Insight [Epub ahead of print]. [https://www.ncbi.nlm.nih.gov/pubmed/36346680 PMID: 36346680 Open Access]
 |authors=Delfinis LJ, Bellissimo CA, Gandhi S, DiBenedetto SN, Garibotti MC, Thuhan AK, Tsitkanou S, Rosa-Caldwell ME, Rahman FA, Cheng AJ, Wiggs MP, Schlattner U, Quadrilatero J, Greene NP, Perry CG
 |year=2022
 |journal=JCI Insight
-|abstract=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 (C26) 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 vs 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 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.
+|abstract=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 (C26) 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 H<sub>2</sub>O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub> emission was unchanged in both muscles vs 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 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.
+|keywords=Colorectal cancer, Metabolism, Mitochondria, Oncology, Skeletal muscle
 |editor=[[Plangger M]]
 }}