Prenatal Programming of Metabolic Syndrome in the Common Marmoset Is Associated With Increased Expression of 11 beta-Hydroxysteroid Dehydrogenase Type 1

Moffat J. Nyirenda, Roderick Carter, Justin I. Tang, Annick de Vries, Christina Schlumbohm, Stephen G. Hillier, Frank Streit, Michael Oellerich, Victor W. Armstrong, Eberhard Fuchs, Jonathan R. Seckl

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVERecent studies in humans and animal models of obesity have shown increased adipose tissue activity of 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1), which amplifies local I issue glucocorticoid concentrations. The reasons for this 11 beta-HSD1 dystegulation are unknown. Here, we tested whether 11 beta-HSD1 expression, like the metabolic syndrome, is "programmed" by prenatal environmental events in a nonhuman primate model, the common marmoset monkey.

RESEARCH DESIGN AND METHODSWe 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 orally for 1 week in either early or late gestation, or they were given vehicle. Tissue 11 beta-HSD1 and glucocorticoid receptor mRNA expression were examined in the offspring at 4 and 24 months of age.

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

CONCLUSIONS These data suggest that long-term upregulation of 11 beta-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.

Original languageEnglish
Pages (from-to)2873-2879
Number of pages7
JournalDiabetes
Volume58
Issue number12
DOIs
Publication statusPublished - Dec 2009

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