It is well established that hypercortisolism (HC) promotes fat redistribution. In our experimental model of HC in rats, we reproduced this phenotype, with an increased mass in mesenteric (32%), perirenal (25%), perigonadal (12%) and omental (12%) fat depots, but an intense reduction (50%) in the retroperitoneal (RP). The increase in central adiposity in HC is not yet fully understood, but is possibly related to alterations in the differentiation and activation of beige adipocytes - the browning.


The aim of this work was to evaluate the gene and protein expression of markers related to browning in the RP deposit in this experimental HC model. For this, 12 weeks old Wistar rats were treated with dexamethasone sodium phosphate 0.5 mg/kg/day (GC group) or vehicle (CT group) for 28 days, through an osmotic minipump. After euthanasia, the RP fat was dissected, and directed to analyzes of gene (qPCR) and protein expression (western blotting).


GC treatment promoted increased UCP1 gene (8.4 fold) and protein (2.2 fold) expression of in the RP fat. GC also increased (p<0.05) the main regulators of UCP1 expression: Prdm16, PGC1╬▒, and PPAR╬│. However, the expression of type 3 beta-adrenergic receptor, the classic pathway of adrenergic activation that regulates UCP1 expression, was reduced (p<0.05) in both gene and protein expression, suggesting a low participation of this pathway in RP fat browning. Finally, GC treatment promoted an increase (p<0.05) of some markers of beige adipocytes such as Pat2, P2rx5, and CD137, but did not alter Cox8b and Tbx1. In addition, there was a reduction (p<0.05) of the Asc1 gene expression, a marker of white adipocytes in this fat pad.


In summary, our results demonstrate that chronic hypercortisolism promotes browning of RP adipose tissue, an effect that could be implicated in the mass reduction ofthis deposit. Our next steps will be to assess if these changes are independent of beta-adrenergic activation, and if other pathways are involved.