Adaptive Programming of IUGR Skeletal Muscle Growth and Metabolism

Our 1st and 2nd studies assessed consequences of adaptive β adrenergic programming in IUGR juvenile skeletal muscle. The objective was to determine if sustained postnatal β2 adrenergic stimulation with clenbuterol rescues deficient muscle growth, body composition, and metabolic efficiency following heat stress-induced IUGR. Birthweights and postnatal weight gains were less for IUGR lambs. They also had reduced muscle, more bodyfat, and increased intramuscular lipid. Moreover, pancreatic insulin secretion was reduced by half and hindlimb glucose oxidation was reduced by more than half, both of which contributed to poor whole-body metabolic homeostasis. Postnatal clenbuterol improved weight gain, muscle growth, adiposity, glucose oxidation, and whole-body metabolism. Because IUGR muscle was responsive to β2 adrenergic stimulation, targeting reduced β2 adrenoreceptor content led to improved muscle growth and body composition in IUGR-born offspring. Our 3rd study sought to determine if reducing inflammation in IUGR fetal sheep with infusion of anti-inflammatory ω-3 fatty acids (EPA) would recover intrinsic deficits in myoblast function and subsequent fetal muscle growth. Myoblast proliferation was less for IUGR and IUGR+EPA fetuses than for controls. Differentiation rates (determined by myogenin) were also less, although desmin expression was greater for myoblasts from IUGR fetuses. Both were improved by fetal EPA infusion. Myoblast deficits contributed to a 30% reduction in muscle mass and a 26% reduction in fetal bodyweight, which were also improved by EPA infusion. These data show that intrinsic deficits in myoblast function are in part due to chronic fetal inflammation and, as such, can be rescued by ω-3 fatty acid treatment. to a 30% reduction in muscle mass and a 26% reduction in fetal bodyweight, which were also improved by EPA infusion. These data show that intrinsic deficits in myoblast function are in part due to chronic fetal inflammation and, as such, can be rescued by ω-3 fatty acid treatment