Background: Sex-specific mechanisms explaining the association between mothers with obesity and the development of obesity in children are poorly characterized. Permanent changes in fetal brain glucocorticoid receptor (GR) expression caused by exposure to overnutrition in utero may program aberrant energy homeostasis, thereby predisposing the offspring to obesity. This study explores sex differences in brain GR expression using an established mouse model of overnutrition during pregnancy. Methods: Female C57Bl/6J mice were fed control (CON) or high-fat–high-sucrose (HFHS) diets. Dam cholesterol, insulin, and triglycerides were measured by colorimetric assays. Fetal corticosterone exposure was measured by placental Abca1, Hsd11β1, Hsd11β2, and brain Nr3c1 (GR); Pomc expression measured by RT-qPCR. Results: Female, but not male, HFHS fetuses had 46% decreased brain GR and twofold increased Pomc expression. There was decreased Abca1 and Hsd11β1 but not Hsd11β2 expression in HFHS placentas. Caloric and sucrose intake, but not fat intake, in dams inversely correlated with fetal GR expression in both sexes. Excess sucrose consumption by dams inversely correlated with female fetal GR and directly correlated with female fetal Pomc expression. Conclusions: Excess sucrose consumption in pregnant dams caused lower GR and higher Pomc expression in the female fetal brain. Clinical investigation of excess sucrose intake during pregnancy and its subsequent effect on hypothalamic-pituitary-adrenal axis activity and appetite in offspring may lead to novel, sex-specific obesity prevention strategies in the development of obesity in children.
Bibliographical noteFunding Information:
The authors thank the Mouse Metabolic Phenotyping Center at the University of Cincinnati (Grant DK59630) for performing colorimetric assay of plasma cholesterol, triglycerides, and insulin. Dr. Paulsen is supported by the National Institute of Health Building Interdisciplinary Research Careers in Women's Health (BIRCWH) grant 5K12HD055887‐14 (MPI).
© 2021 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.
- fetal programming