Gene expression changes in subcutaneous adipose tissue due to cushing’s disease

Abstract

Glucocorticoids have major effects on adipose tissue metabolism. To study tissue mRNA expression changes induced by chronic elevated endogenous glucocorticoids, we performed RNAsequencingonthe subcutaneousadipose tissue frompatientswithCushing’s disease(n=5) compared to patients with nonfunctioning pituitary adenomas (n=11).We found a higher expression of transcripts involved in several metabolic pathways, including lipogenesis, proteolysis and glucose oxidation as well as a decreased expression of transcripts involved in inflammation and protein synthesis. To further study this in amodel system,we subjectedmice todexamethasone treatment for 12weeks andanalyzedtheir inguinal (subcutaneous) fat pads, which led to similar findings. Additionally, mice treated with dexamethasone showed drastic decreases in lean body mass as well as increased fat mass, further supporting the human transcriptomic data. These data provide insight to transcriptional changes that may be responsible for the comorbidities associated with chronic elevations of glucocorticoids.