Hypothalamic–pituitary–adrenal axis activation and glucocorticoid-responsive gene expression in skeletal muscle and liver of Apc mice - Centre de recherche en cancérologie de Lyon (UMR INSERM 1052 ; CNRS 5286 ; Centre Léon Bérard) Accéder directement au contenu
Article Dans Une Revue Journal of Cachexia, Sarcopenia and Muscle Année : 2022

Hypothalamic–pituitary–adrenal axis activation and glucocorticoid-responsive gene expression in skeletal muscle and liver of Apc mice

Barbara Vernus
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Résumé

Background: Cancer patients at advanced stages experience a severe depletion of skeletal muscle compartment together with a decrease in muscle function, known as cancer cachexia. Cachexia contributes to reducing quality of life, treatment efficiency, and lifespan of cancer patients. However, the systemic nature of the syndrome is poorly documented. Here, we hypothesize that glucocorticoids would be important systemic mediators of cancer cachexia. Methods: To explore the role of glucocorticoids during cancer cachexia, biomolecular analyses were performed on several tissues (adrenal glands, blood, hypothalamus, liver, and skeletal muscle) collected from Apc Min/+ male mice, a mouse model of intestine and colon cancer, aged of 13 and 23 weeks, and compared with wild type age-matched C57BL/6J littermates. Results: Twenty-three-week-old Apc mice recapitulated important features of cancer cachexia including body weight loss (À16%, P < 0.0001), muscle atrophy (gastrocnemius muscle: À53%, P < 0.0001), and weakness (À50% in tibialis anterior muscle force, P < 0.0001), increased expression of atrogens (7-fold increase in MuRF1 transcript level, P < 0.0001) and down-regulation of Akt-mTOR pathway (3.3-fold increase in 4EBP1 protein content, P < 0.0001), together with a marked transcriptional rewiring of hepatic metabolism toward an increased expression of gluconeogenic genes (Pcx:
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hal-03616889 , version 1 (23-03-2022)

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Paternité - Pas d'utilisation commerciale - Pas de modification

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Agnès Martin, Josiane Castells, Valentine Allibert, Andréa Emerit, Cindy Zolotoff, et al.. Hypothalamic–pituitary–adrenal axis activation and glucocorticoid-responsive gene expression in skeletal muscle and liver of Apc mice. Journal of Cachexia, Sarcopenia and Muscle, 2022, 13 (3), pp.1686-1703. ⟨10.1002/jcsm.12939⟩. ⟨hal-03616889⟩
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