The impact of glucocorticoid receptor-mediated signaling on the functioning of metabolically stressed mature human adipocytes

01 January 2018 → 31 December 2018
Research Foundation - Flanders (FWO)
Research disciplines
No data available
Project description

Corticosteroids (glucocorticoid hormones) are used worldwide by at least 1% of the world

population to combat inflammation and cancer. A typical corticosteroid-associated weight gain in

patients, common with long-term systemic use, has since long been considered only psychologically

burdening. However, this side effect is now regarded as potentially dangerous since increased

abdominal fat is undoubtedly linked with increased risk of heart disease and type II diabetes. The

molecular basis of adipocyte dysfunction, especially in an inflammatory context, is an understudied

research topic. In addition, recent reports support that obesity, characterized by imbalances in fat

metabolism, is coupled to a chronic low-grade systemic inflammation. Our own work underbuilds

that visceral adipocytes, subject to palmitate as a metabolic stressor, exhibit increased expression of

cytokines. How anti-inflammatory glucocorticoids lead to an accumulation of visceral fat, which

leads to a pro-inflammatory state, is a mechanistically unclear paradox that remains to be solved.

Different ligands that trigger the Glucocorticoid Receptor in different ways have been compared for

their differential gene regulatory profile in healthy versus metabolically stressed mature human

primary adipocyte cells. To provide an explanation for the dysregulated adipocyte functioning upon

glucocorticoid treatment we continue in this project with validations of novel hypotheses based on

RNA sequencing results.