title: CL316,243, a β3-adrenergic receptor agonist, induces muscle hypertrophy and increased strength.
abstract: Studies in vitro have demonstrated that β3-adrenergic receptors (β3-ARs) regulate protein metabolism in skeletal muscle by promoting protein synthesis and inhibiting protein degradation. In this study, we evaluated whether activation of β3-ARs by the selective agonist CL316,243 modifies the functional and structural properties of skeletal muscles of healthy mice. Daily injections of CL316,243 for 15 days resulted in a significant improvement in muscle force production, assessed by grip strength and weight tests, and an increased myofiber cross-sectional area, indicative of muscle hypertrophy. In addition, atomic force microscopy revealed a significant effect of CL316,243 on the transversal stiffness of isolated muscle fibers. Interestingly, the expression level of mammalian target of rapamycin (mTOR) downstream targets and neuronal nitric oxide synthase (NOS) was also found to be enhanced in tibialis anterior and soleus muscles of CL316,243 treated mice, in accordance with previous data linking β3-ARs to mTOR and NOS signaling pathways. In conclusion, our data suggest that CL316,243 systemic administration might be a novel therapeutic strategy worthy of further investigations in conditions of muscle wasting and weakness associated with aging and muscular diseases.
authors.affiliation: Department of Biomedical and Biotechnological Sciences - Section of Physiology, University of Catania, Catania, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Puzzo
authors.affiliation: Department of Informatics, Bioengineering, Robotics, and System Engineering, University of Genova, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Raiteri
authors.affiliation: Department of Public Health, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy.
authors.forename: Clotilde
authors.initials: C
authors.lastname: Castaldo
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Naples, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Capasso
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Naples, Italy.
authors.forename: Ester
authors.initials: E
authors.lastname: Pagano
authors.affiliation: Department of Informatics, Bioengineering, Robotics, and System Engineering, University of Genova, Italy.
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Tedesco
authors.affiliation: Department of Biomedical and Biotechnological Sciences - Section of Physiology, University of Catania, Catania, Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Gulisano
authors.affiliation: Department of Informatics, Bioengineering, Robotics, and System Engineering, University of Genova, Italy.
authors.forename: Lisaveta
authors.initials: L
authors.lastname: Drozd
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Naples, Italy.
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Lippiello
authors.affiliation: Department of Biomedical and Biotechnological Sciences - Section of Physiology, University of Catania, Catania, Italy.
authors.forename: Agostino
authors.initials: A
authors.lastname: Palmeri
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Naples, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Scotto
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Naples, Italy.
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Miniaci
mesh_terms: D058667:Adrenergic beta-3 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004149:Dioxoles / Q000008:administration & dosage / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006984:Hypertrophy; D008297:Male; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000473:pathology; D053580:Muscle Strength / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D004149:Dioxoles; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; D052248:Nitric Oxide Synthase Type I; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases