Adipocytic conversion of 3T3-L1 cells is dependent on induction of tra
nscription factors from the C/EBP family that activate promoters of ad
ipogenic genes, We find that expression of CHOP, a nuclear protein tha
t dimerizes avidly with C/EBP isoforms alpha and beta and directs the
resulting heterodimer away from classic C/EBP-binding sites, markedly
inhibits this differentiation process, Surprisingly, the presence of C
HOP early in the differentiation process inhibits C/EBP alpha and beta
gene expression. Ectopic expression of C/EBP alpha bypasses the inhib
itory effect of CHOP on differentiation, providing further evidence th
at CHOP action is mediated by inhibition of C/EBP alpha gene expressio
n rather than merely inhibiting the encoded protein's DNA-binding acti
vity. A similar pattern of attenuated expression of C/EBP alpha and be
ta is also observed in cells induced to differentiate in media with lo
w glucose concentration. This stressed culture condition is associated
with induction of endogenous CHOP and marked attenuation of the diffe
rentiation process. Our data suggest that CHOP functions as an inducib
le inhibitor of adipocytic differentiation in response to metabolic st
ress. It does so by interfering with the accumulation of adipogenic C/
EBP isoforms.