Depot differences in gene expression in response to dexamethasone in human adipose tissue

Abstract

Hypercortisolemia leads to a preferential fat deposition in visceral adipose tissues. We previously noted that the glucocorticoid receptor agonist dexamethasone (Dex, 25 nM) regulated many metabolic and inflammatory gene pathways in human omental (Om) and abdominal subcutaneous (Sc) adipose tissues. To determine whether differential sensitivity to Dex contributes to depot differences in global gene expression, fragments of Sc and Om adipose tissues from severely obese females (n=3) were cultured in the presence of 7nM insulin plus 0 (control), 1, 10, or 1000 nM Dex for 7 days. 1 and 10 nM Dex regulated, respectively, 88 and 414 genes in Om, and 173 and 594 genes in Sc by 2‐fold or more. Thus, almost 2‐fold more genes were regulated by Dex in Sc than Om at low Dex. We noted and confirmed by qPCR that INHBA, a gene known to inhibit adipogenesis, was ~6‐fold higher in Om and was suppressed in both, but remained higher in Om at Dex 1 and 10 nM. In primary cultured predipocytes (n=3), INHBA was similar in confluent preadipocytes, but was less suppressed when a standard differentiation cocktail containing Dex was added. At day 14 of differentiation, INHBA expression was ~50‐fold higher in Om cultures in parallel to poorer differentiation. Overall, our data suggest that differential sensitivity to physiologically relevant concentrations of Dex can contribute to depot differences in adipocyte differentiation and function.