Prenatal steroid administration leads to adult pericardial and hepatic steatosis in male baboons.
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.
Department of Radiology and Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
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Kuo
Xiangya School of Medicine, Central South University, Changsha, Hunan, China.|Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA.
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Li
Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA.|Department of Animal Science, University of Wyoming, Laramie, WY, USA.
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Li
Department of Animal Science, University of Wyoming, Laramie, WY, USA.
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Huber
Department of Neurology, Jena University Hospital, Jena, Germany.
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Schwab
Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA.|Department of Animal Science, University of Wyoming, Laramie, WY, USA.
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Nathanielsz
Department of Radiology and Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.|Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA.
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Clarke
D000818:Animals; D001623:Betamethasone / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D001724:Birth Weight; D019175:DNA Methylation; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000139:chemically induced* / Q000000981:diagnostic imaging; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D050356:Lipid Metabolism; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D010215:Papio; D010496:Pericardium / Q000000981:diagnostic imaging / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*
D005938:Glucocorticoids; D001623:Betamethasone