The AMP-activated protein kinase (AMPK) activator, 5-aminoimidazole-4-carbo
xamide ribonucleoside (AICAR), has been found to inhibit the differentiatio
n of 3T3-L1 adipocytes, if added at an early phase of differentiation. AICA
R blocks the expression of the late adipogenic markers, fatty acid synthase
and acetyl-CoA carboxylase, and of the transcription factors, C/EBP alpha
and PPAR gamma. It also inhibits early clonal expansion of pre-adipocytes,
prevents the fall in C/EBP beta expression during the intermediate stage of
differentiation and inhibits the late phase expression of CHOP-10, an anta
gonist of C/EBP beta. These data suggest a possible inhibitory role for AMP
K in the process of adipose differentiation and suggest that AMPK might be
a target to block adipogenesis. (C) 2001 Academic Press.