Transcriptomic Evidence that Cortisol Alters Perinatal Epicardial Adipose Tissue Maturation

Cortisol administration during late gestation in ewes, modeling maternal stress, resulted in transcriptomic changes suggesting altered maturation and metabolic changes to the offspring heart. This study investigates the effects of cortisol on epicardial adipose tissue (EAT), a visceral fat pad associated with adverse cardiovascular conditions in adults. Pregnant ewes were treated with either 1 or 0.5 mg/kg/day cortisol from 115 days gestation to term and EAT collected from term fetuses (control: n=8, maternal cortisol 1 mg/kg/day: n=6) or two-week-old lambs (control: n=7, maternal cortisol 0.5mg/kg/day: n=9). Transcriptomic modeling was used to identify pathways altered by maternal cortisol over-exposure. Transcriptomic modeling confirmed the brown fat phenotype of EAT at term and a transition towards white fat at two weeks of age in EAT of control fetuses/lambs, and highlighted a role of immune responses, including complement-coagulation, and serotonin in this transition. Maternal cortisol (1mg/kg/day) increased the lipid peroxidation product 4-hydroxynonenal in EAT of term fetuses, but did not affect the number of activated macrophages or size of the lipid droplets in the depot; transcriptomics suggested an earlier metabolic maturation of EAT via, in part, increased immune responses. Conversely the transcriptomics in EAT of two-week-old lambs of ewes treated with a lower dose of cortisol (0.5mg/kg/day) suggested decreased metabolism of several substrates through both mitochondrial and cytosolic actions, and delayed maturation of EAT associated with a longer period of adipogenesis and angiogenesis. Epicardial adipose tissue was collected from untreated term fetuses (n=8) and naturally born 2-week-old lambs (n=7), and from term fetuses of cortisol-treated ewes (1mg/kg/day) (n=6) or 2-week-old lambs of cortisol treated ewes (0.5mg/kg/day) (n=9).