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.

Beneficial effects of metformin on muscle atrophy induced by obesity in rats

“…It is known that loss of muscle mass impairs the ability to perform daily tasks, increases the incidence of injuries and could be a major risk factor of chronic diseases. 29 The current study showed that rats fed with HFD for 16 weeks gained more body weight and visceral fat when compared with chow fed group. 4 Met is a suggested candidate for lifespan extension, treatment and prevention of sedentariness damages, insulin resistance, and obesity.…”

“…29 Besides, lowering lactate levels in rats, 38 Met decreased the expression of multiple collagen genes indicating its role in attenuation of extracellular matrix (ECM) dysregulation. Met was reported to maintain skeletal muscle mass through activation of AKT.…”

Influenza and obesity: its odd relationship and the lessons for COVID-19 pandemic

“…In contrast, highintensity or prolonged exercise (like running a marathon) is known to deplete the immune response, mainly due to the increase in endogenous cortisol [37]. The basic cellular mechanism via which physical exercise exerts most of its effect is an activation of AMP-kinase [38].…”

Mitochondrial activity and dynamics changes regarding metabolism in ageing and obesity

“…Although rapamycin has been associated with the prevention of age-related diseases and the extension of lifespan in both, obese and lean mice (Liu et al, 2014) and to avoid hyperlipidemia and diabetes-like syndrome in aged obese rats , a recent paper indicate that rapamycin reduces lifespan in the obese db/db mice . In the case of metformin, it has been associated with the prevention of sedentarism-dependent damages (Senesi et al, 2016).…”