INHIBITION OF 3T3-L1 ADIPOCYTE DIFFERENTIATION BY EXPRESSION OF ACYL-COA-BINDING PROTEIN ANTISENSE RNA

Several lines of evidence have recently underscored the significance o f fatty acids or fatty acid-derived metabolites as signaling molecules in adipocyte differentiation. The acyl-CoA-binding protein (ACBP), wh ich functions as an intracellular acyl-CoA pool former and transporter , is induced during adipocyte differentiation. in this report we descr ibe the effects of expression of high levels of ACBP antisense RNA on the differentiation of 3T3-L1 cells. Pools of 3T3-L1 cells transfected with vectors expressing ACBP antisense RNA showed significantly less Lipid accumulation as compared with cells transfected with the control vector. When individual clones were analyzed the degree of differenti ation at day 10 was inversely correlated with the level of ACBP antise nse RNA expression at day 0, Furthermore, in the clones with the highe st levels of ACBP antisense expression, the induction of expression of the adipogenic transcription factors peroxisome proliferator-activate d receptor gamma and CCAAT/enhancer-binding protein alpha as well as s everal adipocyte-specific genes was significantly delayed and reduced. The adipogenic potential of antisense-expressing cells was partially restored by transfection with a vector expressing high levels of ACBP. Taken together, these results are strong evidence that inhibition of differentiation is causally related to the decreased expression of ACB P, indicating that ACBP plays an important role during adipocyte diffe rentiation.