Iron supplementation is sufficient to rescue skeletal muscle mass and function in cancer cachexia.
cachexia
iron
metabolism
mitochondria
muscle
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
05 04 2022
05 04 2022
Historique:
revised:
20
01
2022
received:
03
08
2021
accepted:
25
01
2022
pubmed:
25
2
2022
medline:
8
4
2022
entrez:
24
2
2022
Statut:
ppublish
Résumé
Cachexia is a wasting syndrome characterized by devastating skeletal muscle atrophy that dramatically increases mortality in various diseases, most notably in cancer patients with a penetrance of up to 80%. Knowledge regarding the mechanism of cancer-induced cachexia remains very scarce, making cachexia an unmet medical need. In this study, we discovered strong alterations of iron metabolism in the skeletal muscle of both cancer patients and tumor-bearing mice, characterized by decreased iron availability in mitochondria. We found that modulation of iron levels directly influences myotube size in vitro and muscle mass in otherwise healthy mice. Furthermore, iron supplementation was sufficient to preserve both muscle function and mass, prolong survival in tumor-bearing mice, and even rescues strength in human subjects within an unexpectedly short time frame. Importantly, iron supplementation refuels mitochondrial oxidative metabolism and energy production. Overall, our findings provide new mechanistic insights in cancer-induced skeletal muscle wasting, and support targeting iron metabolism as a potential therapeutic option for muscle wasting diseases.
Identifiants
pubmed: 35199910
doi: 10.15252/embr.202153746
pmc: PMC8982578
doi:
Substances chimiques
Iron
E1UOL152H7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e53746Informations de copyright
© 2022 The Authors. Published under the terms of the CC BY 4.0 license.
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