title: Metformin Treatment Prevents Sedentariness Related Damages in Mice.
abstract: Metformin (METF), historical antihyperglycemic drug, is a likely candidate for lifespan extension, treatment and prevention of sedentariness damages, insulin resistance, and obesity. Skeletal muscle is a highly adaptable tissue, capable of hypertrophy response to resistance training and of regeneration after damage. Aims of this work were to investigate METF ability to prevent sedentariness damage and to enhance skeletal muscle function. Sedentary 12-week-old C57BL/6 mice were treated with METF (250 mg/kg per day, in drinking water) for 60 days. METF role on skeletal muscle differentiation was studied in vitro using murine C2C12 myoblasts. Muscular performance evaluation revealed that METF enhanced mice physical performance (Estimated VO2max). Biochemical analyses of hepatic and muscular tissues indicated that in liver METF increased AMPK and CAMKII signaling. In contrast, METF inactivated ERKs, the principal kinases involved in hepatic stress. In skeletal muscle, METF activated AKT, key kinase in skeletal muscle mass maintenance. In in vitro studies, METF did not modify the C2C12 proliferation capacity, while it positively influenced the differentiation process and myotube maturation. In conclusion, our novel results suggest that METF has a positive action not only on the promotion of healthy aging but also on the prevention of sedentariness damages.
authors.affiliation: Department of Biomedical Sciences for Health, University of Milan, Milan, Italy ; Metabolism Research Center, San Donato Hospital and Scientific Institute, Milan, Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Senesi
authors.affiliation: Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Montesano
authors.affiliation: Department of Biomedical Sciences for Health, University of Milan, Milan, Italy ; Metabolism Research Center, San Donato Hospital and Scientific Institute, Milan, Italy.
authors.forename: Livio
authors.initials: L
authors.lastname: Luzi
authors.affiliation: Department of Biomedical Sciences for Health, University of Milan, Milan, Italy ; Metabolism Research Center, San Donato Hospital and Scientific Institute, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Codella
authors.affiliation: Department of Biomedical Sciences for Health, University of Milan, Milan, Italy ; Metabolism Research Center, San Donato Hospital and Scientific Institute, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Benedini
authors.affiliation: Diabetes Research Institute, Metabolism, Nutrigenomics and Cellular Differentiation Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Ileana
authors.initials: I
authors.lastname: Terruzzi
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism; D057185:Sedentary Behavior; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2