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), 11beta-hydroxysteroid dehydrogenase (11betaHSD) 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 approximately 147 days)- or late (110-147 days) gestation. GR and 11betaHSD1 mRNA increased with fat mass and were all maximal within the 6-mo observation period. 11betaHSD2 mRNA abundance demonstrated a converse decline, whereas UCP2 peaked at 30 days. GR and 11betaHSD1 mRNA abundance were strongly correlated with total and relative perirenal adipose tissue weight, and UCP2 was strongly correlated with GR and 11betaHSD1 mRNA. Early- to midgestational NR increased GR, 11betaHSD1, and UCP2 mRNA, but decreased 11betaHSD2 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.
Centre for Reproduction and Early Life, Institute of Chemical Research, University of Nottingham, United Kingdom.
Muhuntha G
MG
Gnanalingham
Alison
A
Mostyn
Michael E
ME
Symonds
Terence
T
Stephenson
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D049628:Body Size; D005260:Female; D047109:Fetal Development; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D005938:Glucocorticoids / Q000378:metabolism*; D007473:Ion Channels; D026901:Membrane Transport Proteins / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009765:Obesity / Q000209:etiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D039401:Prenatal Nutritional Physiological Phenomena / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D034561:Sheep, Domestic; D000071246:Uncoupling Protein 2
D005938:Glucocorticoids; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D000071246:Uncoupling Protein 2; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2