Characterization of the rodent genes for arylacetamide deacetylase, a putative microsomal lipase, and evidence for transcriptional regulation

In the current study, we have determined the cDNA and the genomic sequences of the arylacetamide deacetylase (AADA) gene in mice and rats. The AADA ge nes in the rat and mouse consist of five exons and have 2.4 kilobases of ho mologous promoter sequence upstream of the initiating ATG codon. AADA mRNA is expressed in hepatocytes, intestinal mucosal cells (probably enterocytes ), the pancreas and also the adrenal gland. In mice, there is a diurnal rhy thm in hepatic AADA mRNA concentration, with a maximum 10 h into the light (post-absorptive) phase. This diurnal regulation is attenuated in peroxisom e proliferator-activated receptor a knockout mice. Intestinal but not hepat ic AADA mRNA was increased following oral administration of the fibrate, Wy -14,643. The homology of AADA with hormone-sensitive lipase and the tissue distribution of AADA are consistent with the view that AADA plays a role in promoting the mobilization of lipids from intracellular stores and in the liver for assembling VLDL This hypothesis is supported by parallel changes in AADA gene expression in animals with insulin-deficient diabetes and foll owing treatment with orotic acid.