Abstract
Developmental programming studies indicate that glucocorticoids modify fetal development. We hypothesized that administration of the synthetic glucocorticoid (sGC) betamethasone to pregnant baboons at doses and stages of fetal life equivalent to human obstetric practice to decrease premature offspring morbidity and mortality, programs lipid metabolism. In 10-year-old male baboons (human equivalent 40) exposed in fetal life to betamethasone or saline, we quantified pericardial fat and hepatic lipid content with magnetic resonance imaging and spectroscopy. sGC offspring delivered at term as do most sGC-exposed human neonates. Pericardial fat thickness (7.7±3.6 mm vs 3.1±1.1 mm, M±s.d.; P=0.022; n=5) and hepatic fatty acids (13.3±11.0% vs 2.5±2.2%; P=0.046; n=5) increased following sGC without birth weight or current body morphometric differences. Our results indicate that antenatal sGC therapy caused abnormal fat deposition and adult body composition in mid-life primate offspring. The concern raised is that this degree of pericardial and hepatic lipid accumulation can lead to harmful local lipotoxicity. In summary, developmental programing by sGC produces a mid-life metabolically obese but normal weight phenotype. Prior studies show sexually dimorphic responses to some programming challenges thus female studies are necessary.
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Acknowledgements
We thank Dr Robert Lanford and the Southwest National Primate Center staff for their ongoing technical support of our baboon research program described in this article. We also acknowledge the technical support of Steven Rios, Sam Vega, McKenna Considine, and Susan Jenkins, as well as the administrative support of Karen Moore. This work was supported by the National Institutes of Health (5P01HD021350 to PWN, 5R24OD011183 to PWN, 5K25DK089012 to GDC, 1R25EB016631 to AHK, and OD P51 OD011133 from the Office of Research Infrastructure Programs/Office of the Director); EU FP 7/HEALTH/GA No.: 279281: BrainAge - Impact of Prenatal Stress on BRAINAGEing.
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Kuo, A., Li, J., Li, C. et al. Prenatal steroid administration leads to adult pericardial and hepatic steatosis in male baboons. Int J Obes 41, 1299–1302 (2017). https://doi.org/10.1038/ijo.2017.82
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DOI: https://doi.org/10.1038/ijo.2017.82