Fat Redistribution in an Experimental Model of Hypercortisolism in Rats
Authors: De Fatima Silva Flaviane , Komino Ayumi Cristina Medeiros , Andreotti Sandra , Reis Gabriela Boltes , Lima Fabio Bessa 
Published: June 2021

Chronic iatrogenic hypercortisolism, which is associated with the inhibition of the adrenal‐pituitary‐ hypothalamic axis, shows characteristic signs that are seen in different forms of Cushing's syndrome. In humans, fat redistribution with increased visceral obesity is one of the main metabolic changes in this syndrome that is related to the development of the metabolic syndrome (insulin resistance, dyslipidemia, and hypertension). However, the mechanisms of fat redistribution between different depots have not been fully elucidated yet, which can be clarified with the establishment of an experimental animal model for Cushing's syndrome.The aim of this study was to characterize the fat redistribution in an experimental model of hypercortisolism in rats (approved by the Ethics Committee in Animal Research [CEUA‐ICB/USP 89/2016]). Male Wistar SPF rats (12 weeks old) were used in experiments. The glucocorticoid (GC) [dexamethasone sodium phosphate 0.5 mg/kg/day] was continuously administered during 4 weeks, by an osmotic pump surgically implanted in the interscapular region. Control (CT) rats were submitted to the same procedure but with NaCl 0.9% administration. Adrenal glands (histologically examined, HE staining) and inguinal subcutaneous, mesenteric and perirenal fat were collected after euthanasia, weighed and the fat was enzymatically digested for adipocyte isolation and morphologic analysis (Motic‐Image Plus 3.0). GC treatment promoted reduction (60%, p<0.0001) of adrenal mass, and the gland atrophy can be verified by qualitative histological analysis. The treatment also promoted intense loss of body mass (150% lower, p<0.0001) and a reduction of 9% (p<0.0001) of the Lee index. However, the rats treated with GC showed an increase of 29% of visceral fat mass represented by mesenteric (p<0.01) and perirenal (p<0.05) depots. Although these depots showed an increased mass, no difference was observed in adipocyte number and volume in the mesenteric fat, whereas in the perirenal, the cell number was higher (p <0.001) and adipocyte volume was lower (p<0.01). Additionally, no difference was observed in inguinal subcutaneous fat mass in GC treated rats. In fact, there was no change in the cellularity of this fat depot, but the adipocyte volume of the GC treated rats was lower in comparison to the CT group. In conclusion, we showed that chronic GC treatment promotes adipose remodeling inducing increased visceral fat mass, reproducing an important characteristic of Cushing's syndrome in humans. This remodeling is certainly associated with several processes that affect lipolysis/lipogenesis, apoptosis/adipogenesis and maybe browning/whitening balances which mechanisms underlying them are now under intense investigation in our laboratory.Support or Funding InformationFAPESP (2016/25129‐4) and CNPq (170545/2017‐2)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.