Ontogeny and nutritional programming of adiposity in sheep: potential role of glucocorticoid action and uncoupling protein-2

Increased glucocorticoid action and adipose tissue inflammation contribute to excess adiposity. These adaptations may be enhanced in offspring exposed to nutrient restriction (NR) in utero, thereby increasing their susceptibility to later obesity. We therefore determined the developmental ontogeny of glucocorticoid receptor (GR), 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) types 1 and 2, and uncoupling protein (UCP)-2 mRNA in perirenal adipose tissue between late gestation and 6 mo after birth in the sheep, as well as the effect of maternal NR targeted between early to mid (28-80 days, term similar to 147 days)- or late (110-147 days) gestation. GR and 11 beta HSD1 mRNA increased with fat mass and were all maximal within the 6-mo observation period. 11 beta HSD2 mRNA abundance demonstrated a converse decline, whereas UCP2 peaked at 30 days. GR and 11 beta HSD1 mRNA abundance were strongly correlated with total and relative perirenal adipose tissue weight, and UCP2 was strongly correlated with GR and 11 beta HSD1 mRNA. Early-to midgestational NR increased GR, 11 beta HSD1, and UCP2 mRNA, but decreased 11 beta HSD2 mRNA abundance, an adaptation reversed with late-gestational NR. We conclude that the continual rise in glucocorticoid action and fat mass after birth may underlie the development of later obesity. The magnitude of this adaptation is partly dependent on maternal food intake through pregnancy.