Cardiac fibrosis alleviated by exercise training is AMPK-dependent

Abstract

Regular exercise can protect the heart against external stimuli, but the mechanism is not well understood. We determined the role of adenosine monophosphate-activated protein kinase (AMPK) in regulating swimming exercise-mediated cardiac protection against β-adrenergic receptor overstimulation with isoproterenol (ISO) in mice. Ten-week-old AMPKα2 +/ + and AMPKα2-knockout (AMPKα2 -/-) littermates were subjected to 4 weeks of swimming training (50 min daily, 6 days a week) or housed under sedentary conditions. The mice received daily subcutaneous injection of ISO (5 mg/kg/d), a nonselective β-adrenergic receptor agonist, during the last 2 weeks of swimming training. Swimming training alleviated ISO-induced cardiac fibrosis in AMPKα2 +/+ mice but not AMPKα2 AMPKα2-/-mice. Swimming training activated cardiac AMPK in AMPKα2 +/+ mice. Furthermore, swimming training attenuated ISO-induced production of reactive oxygen species (ROS) and expression of NADPH oxidase and promoted the expression of antioxidant enzymes in AMPKα2 +/+ mice but not AMPKα2 -/- mice. In conclusion, swimming training attenuates ISO-induced cardiac fibrosis by inhibiting the NADPH oxidase-ROS pathway mediated by AMPK activation. Our findings provide a new mechanism for the cardioprotective effects of exercise.