V. Zilberfarb et al., Effect of dexamethasone on adipocyte differentiation markers and tumour necrosis factor-alpha expression in human PAZ6 cells, DIABETOLOG, 44(3), 2001, pp. 377-386
Aims/hypothesis. Adipose tissue-derived tumour necrosis factor-alpha (TNF-a
lpha) has been implicated in the insulin resistance observed in animal mode
ls of obesity. Moreover, TNF-alpha has inhibitory effects on adipocyte diff
erentiation. Glucocorticoids play important roles in the regulation of insu
lin sensitivity and adipose tissue distribution. We therefore studied the e
ffect of dexamethasone on TNF-alpha expression and adipocyte differentiatio
n in human PAZ6 cells.
Methods. The expression of TNF-alpha and adipocyte differentiation markers
was assessed by reverse-transcription polymerase chain reaction in PAZ6 cel
ls.
Results. In cells cultured for 15 days in the presence of dexamethasone, ad
ipocyte differentiation marker expression was higher and TNF-alpha expressi
on was lower than in cells cultured in the absence of dexamethasone. The pr
esence of dexamethasone was necessary during the whole period of differenti
ation because removal of dexamethasone during the second week resulted in p
oorly differentiated adipocytes that express higher levels of TNF-alpha.
Dexamethasone also reduced TNF-alpha expression during early stages of diff
erentiation. The use of a TNF-alpha -neutralising antibody showed, however,
that endogenously-produced TNF-alpha did not play an important part in the
control of PAZ6 cell differentiation. During early stages of adipocyte dif
ferentiation, dexamethasone induced the expression of the transcription fac
tors PPAR gamma (peroxisome proliferator activated receptor gamma) and C/BP
alpha (CCAAT/enhancer binding protein a) while inhibiting the expression o
f the inhibitor of DNA binding Id2.
Conclusion/interpretation. The effect of dexamethasone on human adipocyte d
ifferentiation is not mediated by reduction of TNF-alpha expression but mor
e likely by regulation of the expression of nuclear factors such as PPAR ga
mma, CEBP alpha and Id2.