Prenatal steroid administration leads to adult pericardial and hepatic steatosis in male baboons

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.

Figure 1. Prenatal betamethasone administration results in increased pericardial fat deposition

Sample short axis images depicting increased amount of pericardial fat in sGC subjects (A, arrow) compared to CTL (B) at the level of mid-ventricle. With quantification, pericardial fat thickness was higher in the sGC group (7.7 ± 3.6 mm, n = 5) compared to CTL (3.1 ± 1.1 mm, n = 5, p = 0.022).

Figure 2. Prenatal betamethasone administration results in increased hepatic steatosis

Sample raw hepatic magnetic resonance spectra depicting increased amount of hepatic fatty acids in sGC subjects (A) compared to CTL (B). Overall hepatic fat content was higher in the sGC animals (13.3 ± 11.0 %, n = 5) compared to CTL (2.5 ± 2.2 %, n = 5, p = 0.046).