Abstract

Objective- Recent studies in humans and animal models of obesity have shown increased adipose tissue activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which amplifies local tissue glucocorticoid concentrations. The reasons for this 11β-HSD1 dysregulation are unknown. Here, we tested whether 11β-HSD1 expression, like the metabolic syndrome, is ‘programmed’ by prenatal environmental events in a non-human primate model, the common marmoset monkey.

Research design and methods- We used a ‘fetal programming’ paradigm where brief antenatal exposure to glucocorticoids leads to the metabolic syndrome in the offspring. Pregnant marmosets were given the synthetic glucocorticoid dexamethasone (DEX) orally for one week in either early or late gestation or vehicle. Tissue 11β-HSD1 and glucocorticoid receptor (GR) mRNA expression were examined in the offspring at 4 and 24 months of age.

Results- Prenatal DEX treatment, selectively during late gestation, resulted in early and persistent elevations in 11β-HSD1 mRNA expression and activity in the liver, pancreas and subcutaneous, but not visceral fat. The increase in 11β-HSD1 occurred before animals developed obesity or overt features of the metabolic syndrome. In contrast to rodents, in utero DEX exposure did not alter GR expression in metabolic tissues in marmosets.

Conclusions- These data suggest that longterm up-regulation of 11β-HSD1 in metabolically active tissues may follow prenatal ‘stress’ hormone exposure and indicates a novel mechanism for fetal origins of adult obesity and the metabolic syndrome.