Prenatal Programming of Metabolic Syndrome in the Common Marmoset Is Associated With Increased Expression of 11β-Hydroxysteroid Dehydrogenase Type 1
Open Access
- 31 August 2009
- journal article
- research article
- Published by American Diabetes Association in Diabetes
- Vol. 58 (12), 2873-2879
- https://doi.org/10.2337/db09-0873
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 nonhuman 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 orally for 1 week in either early or late gestation, or they were given vehicle. Tissue 11β-HSD1 and glucocorticoid receptor mRNA expression were examined in the offspring at 4 and 24 months of age. RESULTS Prenatal dexamethasone administration, 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 dexamethasone exposure did not alter glucocorticoid receptor expression in metabolic tissues in marmosets. CONCLUSIONS These data suggest that long-term upregulation 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.Keywords
This publication has 38 references indexed in Scilit:
- Early life programming of obesity and metabolic diseasePhysiology & Behavior, 2008
- Diabetic pregnancy in rats leads to impaired glucose metabolism in offspring involving tissue-specific dysregulation of 11β-hydroxysteroid dehydrogenase type 1 expressionLife Sciences, 2007
- Mechanisms underlying the role of glucocorticoids in the early life programming of adult diseaseClinical Science, 2007
- Type 2 diabetes and metabolic syndrome are associated with increased expression of 11β-hydroxysteroid dehydrogenase 1 in obese subjectsInternational Journal of Obesity, 2007
- Prenatal dexamethasone exposure induces changes in nonhuman primate offspring cardiometabolic and hypothalamic-pituitary-adrenal axis functionJCI Insight, 2007
- Increased expression and activity of 11β-HSD-1 in diabetic islets and prevention with troglitazoneBiochemical and Biophysical Research Communications, 2004
- Understanding the Role of Glucocorticoids in Obesity: Tissue-Specific Alterations of Corticosterone Metabolism in Obese Zucker RatsEndocrinology, 2000
- Glucocorticoid exposure in late gestation permanently programs rat hepatic phosphoenolpyruvate carboxykinase and glucocorticoid receptor expression and causes glucose intolerance in adult offspring.JCI Insight, 1998
- Elevated Plasma Cortisol Concentrations: A Link between Low Birth Weight and the Insulin Resistance Syndrome?Journal of Clinical Endocrinology & Metabolism, 1998
- Direct glucocorticoid inhibition of insulin secretion. An in vitro study of dexamethasone effects in mouse islets.JCI Insight, 1997