Stimulation of adipose differentiation related protein (ADRP) expression in adipocyte precursors by long-chain fatty acids.

Abstract

Adipose differentiation related protein (ADRP) is a 50-kDa protein expressed in adipocytes and transcriptionally activated when adipocyte precursors differentiate into mature adipocytes. Recent experiments have demonstrated that ADRP is a fatty acid binding protein that specifically facilitates the uptake of long-chain fatty acids. The present investigation provides evidence that ADRP mRNA and protein expression in preadipocytes is stimulated by fatty acids in a time- and dose-dependent fashion. ADRP mRNA expression was maximally stimulated at fatty acid concentrations of or above 10(-5) M. Stimulation of ADRP expression was observed with the nonmetabolizable fatty acid 2-bromopalmitate and with natural fatty acids. Stimulation of ADRP mRNA expression by fatty acids peaked between 5 and 8 hr and decreased by 24 hr. Stimulation of ADRP expression by fatty acids was completely inhibited by treatment with actinomycin D, suggesting that fatty acid stimulates ADRP gene expression at the transcriptional level. Comparison of the effect of several fatty acids with varying carbon chain lengths indicated that long-chain fatty acids were active in stimulating ADRP, whereas short-chain fatty acids such as caproate and 2-bromooctanoate had no effect. The degree of saturation of fatty acids did not influence their ability to stimulate ADRP expression. These studies provide new information on the regulation of ADRP and identify a new target regulated by fatty acids during adipose differentiation.