Iron supplementation is sufficient to rescue skeletal muscle mass and function in cancer cachexia

Autor: Elisabeth Wyart, Myriam Y Hsu, Roberta Sartori, Erica Mina, Valentina Rausch, Elisa S Pierobon, Mariarosa Mezzanotte, Camilla Pezzini, Laure B Bindels, Andrea Lauria, Fabio Penna, Emilio Hirsch, Miriam Martini, Massimiliano Mazzone, Antonella Roetto, Simonetta Geninatti Crich, Hans Prenen, Marco Sandri, Alessio Menga, Paolo E Porporato
Přispěvatelé: UCL - SSS/LDRI - Louvain Drug Research Institute
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: EMBO reports, Vol. 23, no. 4, p. e53746 [1-18] (2022)
EMBO reports
ISSN: 1469-221X
Popis: 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. ispartof: EMBO REPORTS vol:23 issue:4 ispartof: location:England status: published
Databáze: OpenAIRE
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