CLONING OF A PROTEIN THAT MEDIATES TRANSCRIPTIONAL EFFECTS OF FATTY-ACIDS IN PREADIPOCYTES - HOMOLOGY TO PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS

Exposure of preadipocytes to long chain fatty acids induces expression of several gene markers of adipocyte differentiation. This report des cribes the cloning, from a preadipocyte library, of a cDNA encoding a fatty acid-activated receptor, FAAR. The cDNA had the characteristics and ligand-binding domains of nuclear hormone receptors and encoded a 440 amino acid protein related to peroxisome proliferator-activated re ceptors, PPAR. The deduced protein sequence was 88% homologous to that of hNUC I, isolated from human osteosarcoma cells, FAAR mRNA was abun dant in adipose tissue, intestine, brain, heart, and skeletal muscles and less abundant in kidney, liver, testis, and spleen, The mRNA was u ndetectable in growing Ob1771 and 3T3-F442A preadipocytes, was strongl y induced early during differentiation, and was increased by fatty aci d, Transcription assays using hybrid receptor showed strong stimulatio n by fatty acid and weaker induction by fibrates, Transfection of 3T3- C2 fibroblasts, with a FAAR expression vector, conferred fatty acid in ducibility of the adipocyte lipid-binding protein and the fatty acid t ransporter, Transcriptional induction of these genes exhibited inducer specificity identical to that described in preadipocytes, In summary, the data indicate that FAAR is likely a mediator of fatty acid transc riptional effects in preadipocytes.