Preweaning GH Treatment Normalizes Body Growth Trajectory and Reverses Metabolic Dysregulation in Adult Offspring After Maternal Undernutrition

Abstract

Maternal undernutrition (UN) results in growth disorders and metabolic dysfunction in offspring. Although dysregulation of the GH-IGF axis in offspring is a known consequence of maternal UN, little is known about the efficacy of GH treatment during the period of developmental plasticity on later growth and metabolic outcomes. The present study investigated the effect of preweaning GH treatment on growth, glucose metabolism, and the GH-IGF axis in adult male and female offspring after maternal UN. Female Sprague Dawley rats were fed either a chow diet ad libitum (control [CON]) or 50% of ad libitum (UN) throughout pregnancy. From postnatal day 3, CON and UN pups received either saline (CON-S and UN-S) or GH (2.5 μg/g·d CON-GH and UN-GH) daily throughout lactation. At weaning, male and female offspring were randomly selected from each litter and fed a standard chow diet for the remainder of the study. Preweaning GH treatment normalized maternal UN-induced alterations in postweaning growth trajectory and concomitant adiposity in offspring. Plasma leptin concentrations were increased in UN-S offspring and normalized in the UN-GH group. Hepatic GH receptor expression was significantly elevated in UN-S offspring and normalized with GH treatment. Hepatic IGF binding protein-2 gene expression and plasma IGF-1 to IGF binding protein-3 ratio was reduced in UN-S offspring and elevated with GH treatment. GH treatment during a critical developmental window prevented maternal UN-induced changes in postnatal growth patterns and related adiposity, suggesting that manipulation of the GH-IGF-1 axis in early development may represent a promising avenue to prevent adverse developmental programming effects in adulthood.