Endocrine Abstracts

Cushing syndrome is a comorbid condition resulting from long-term exposure to glucocorticoids (GC). It affects body fat composition in various parts of the body. Since each fat depot has a distinct response to glucocorticoid exposure, we wanted to understand adipose tissue turnover. In order to reproduce the disease state, we used a rodent model recapitulating Cushing syndrome. We inserted subcutaneous mini pumps in the dorsal area of rats to infuse Dexamethasone at a rate of 187.5 µg/day, for 4 months. Dexamethasone is a synthetic analog of human cortisol. We collected different fat depots. We observed that total epididymal (EP) fat weight was proportionately lower as the total body weight of the animal. Similarly, the adipocyte size and volume were negatively redistributed. We also found that exposure to Dexa for 48 hrs, decreased incorporation of glycerol, fatty acids and lipids. There was an increase of glycerol release, from epididymal adipocytes, which likely resulted in decrease in lower EP mass. We then explored the mechanism of adipocytes turnover in Dexa treated animals. We found that adipogenesis and apoptosis pathways were altered resulting in the redistribution of the fat. We observed that EP tissue had lower phosphorylation of caspase 3, 8 and 9 in Dexa treated compared to untreated group, while adipocytes from Dexa-induced rats showed upregulation of adipogenic markers, as PPARγ, CEBPα, and SREBP1. However, pre-adipocytes derived from Dexa treated animals revealed lower lipogenesis. The resistance to incorporate lipids might be affecting the commitment of those cells to matured. In summary, the mature adipocytes from EP fat tissue have higher adipogenic markers and low activation of cell death pathways which could explain the phenotype of Cushing syndrome.