The Effect of Downhill Running on Quadriceps Muscle in Growth-Restricted Mice

Abstract

Introduction Growth-restriction (GR) reduces ribosome abundance and skeletal muscle mass in mice. A reduction in skeletal muscle mass increases the risk of frailty and is associated with high morbidity and mortality rates. As eccentric type exercise increases muscle mass, this investigation aimed to determine if eccentric loading of skeletal muscle via downhill running (DHR) increased muscle mass in GR mice. Methods Mice were growth-restricted either gestational undernutrition (GUN: n = 8 litters), postnatal undernutrition (PUN: n = 8 litters) or were not restricted (CON: n = 8 litters) via a validated cross-fostering nutritive model. On postnatal day (PN) 21, all mice were weaned to a healthy diet, isolating the period of GR to early life as seen in humans. At PN45, mice were assigned to either a downhill running (DHR, CON n = 4 litters, GUN n = 4 litters, PUN n = 4 litters) or sedentary (SED, CON n = 4 litters, GUN n = 4 litters, PUN n = 4 litters) group. DHR (16% decline: 18 m/min) was performed in 30-minute bouts, three times per week, for 12 weeks on a rodent treadmill. At PN129, the quadriceps femoris was dissected and evaluated for mass, myofiber size and type, and molecular markers of growth. Results Following training, CON-DHR mice having larger cells than CON-SED, GUN-SED, PUN-SED, and PUN-DHR mice (p < 0.05). The PUN group (as compared to CON) had reduced body mass (p < 0.001), UBF abundance (p = 0.012), phosphor-mTOR (p < 0.001), and quadriceps mass (p = 0.02). The GUN and PUN groups had increased MuRF1 abundance (p < 0.001) compared to CON (p < 0.001). Conclusions The blunted response to training suggests GR mice may have anabolic resistance when exposed to eccentric type exercise.