Prenatal T excess causes reproductive and metabolic disruptions including
insulin resistance, attributes of women with
polycystic ovary syndrome. This study tested whether increases in visceral adiposity, adipocyte size, and total
free fatty acids underlie the
insulin resistance seen in prenatal T-treated female sheep. At approximately 16 months of age,
insulin resistance and adipose tissue partitioning were determined via hyperinsulinemic euglycemic clamp and computed tomography, respectively, in control and prenatal T-treated females. Three months later, adipocyte size and
free fatty acid composition were determined. Results revealed that at the postpubertal time points tested,
insulin sensitivity was increased, visceral adiposity and adipocyte size in both the sc and the visceral compartments were reduced, and circulating
palmitic acid was increased in prenatal T-treated females relative to controls. In parallel studies, 20-month-old prenatal T-treated females tended to have increased basal
insulin to
glucose ratio. Relative to earlier findings of reduced
insulin sensitivity of prenatal T-treated females during early life and adulthood, these findings of increased
insulin sensitivity and reduced adiposity postpubertally are suggestive of a period of developmental adaptation. The disruption observed in
free fatty acid metabolism a few months later correspond to a time point when the
insulin sensitivity indices of prenatal T-treated animals appear to shift toward
insulin resistance. In summary, current findings of improved
insulin sensitivity and reduced visceral adiposity in postpubertal prenatal T-treated sheep relative to our earlier findings of reduced
insulin sensitivity during early postnatal life and adulthood are indicative of a period of developmental adaptation.