Effect of dexamethasone on adipocyte differentiation markers and tumour necrosis factor-α expression in human PAZ6 cells

Abstract

Aims/hypothesis. Adipose tissue-derived tumour necrosis factor-α (TNF-α) has been implicated in the insulin resistance observed in animal models of obesity. Moreover, TNF-α has inhibitory effects on adipocyte differentiation. Glucocorticoids play important roles in the regulation of insulin sensitivity and adipose tissue distribution. We therefore studied the effect of dexamethasone on TNF-α expression and adipocyte differentiation in human PAZ6 cells. Methods. The expression of TNF-α and adipocyte differentiation markers was assessed by reverse-transcription polymerase chain reaction in PAZ6 cells. Results. In cells cultured for 15 days in the presence of dexamethasone, adipocyte differentiation marker expression was higher and TNF-α expression was lower than in cells cultured in the absence of dexamethasone. The presence of dexamethasone was necessary during the whole period of differentiation because removal of dexamethasone during the second week resulted in poorly differentiated adipocytes that express higher levels of TNF-α. Dexamethasone also reduced TNF-α expression during early stages of differentiation. The use of a TNF-α-neutralising antibody showed, however, that endogenously-produced TNF-α did not play an important part in the control of PAZ6 cell differentiation. During early stages of adipocyte differentiation, dexamethasone induced the expression of the transcription factors PPARγ (peroxisome proliferator activated receptor γ) and C/EBPα (CCAAT/enhancer binding protein α) while inhibiting the expression of the inhibitor of DNA binding Id2. Conclusion/interpretation. The effect of dexamethasone on human adipocyte differentiation is not mediated by reduction of TNF-α expression but more likely by regulation of the expression of nuclear factors such as PPARγ, CEBPγ and Id2.