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Cellular mechanisms underlying temporal changes in skeletal muscle protein synthesis and breakdown during chronic β‐adrenoceptor stimulation in mice
Author(s) -
Koopman René,
Gehrig Stefan M.,
Léger Bertrand,
Trieu Jennifer,
Walrand Stéphane,
Murphy Kate T.,
Lynch Gordon S.
Publication year - 2010
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2010.196725
Subject(s) - medicine , endocrinology , skeletal muscle , formoterol , stimulation , muscle hypertrophy , protein kinase b , chemistry , anabolism , phosphorylation , biology , biochemistry , budesonide , corticosteroid
Chronic stimulation of β‐adrenoceptors with β‐adrenoceptor agonists (β‐agonists) can induce substantial skeletal muscle hypertrophy, but the mechanisms mediating this muscle growth have yet to be elucidated. We investigated whether chronic β‐adrenoceptor stimulation in mice with the β‐agonist formoterol alters the muscle anabolic response following β‐adrenoceptor stimulation. Twelve‐week‐old C57BL/6 mice were treated for up to 28 days with a once‐daily injection of either saline (control, n = 9) or formoterol (100 μg kg −1 ; n = 9). Rates of muscle protein synthesis were assessed at either 1, 7 or 28 days of treatment, 6 h after injection. Protein synthesis rates were higher in formoterol‐treated mice at day 7 (∼1.5‐fold, P < 0.05), but not at day 1 or 28. The increased muscle protein synthesis was associated with increased phosphorylation of S6K1 ( r = 0.49, P < 0.01). Formoterol treatment acutely reduced maximal calpain activity by ∼25% ( P < 0.05) but did not affect atrogin‐1 protein levels and proteasome‐mediated proteolytic activity, despite significantly enhanced phosphorylation of Akt ( P < 0.05). Formoterol increased CREB phosphorylation by ∼30% ( P < 0.05) and PPARγ coactivator‐1α (PGC‐1α) by 11‐fold ( P < 0.05) on day 1 only. These observations identify that formoterol treatment induces muscle anabolism, by reducing calpain activity and by enhancing protein synthesis via increased PI‐3 kinase/Akt signalling.