Insulin/glucose-, pyruvate- and polyunsaturated fatty acid-responsive region(s) of rat fatty acid synthase gene promoter

To investigate the regulatory DNA sequences required for polyunsaturated fatty acid (PUFA)-suppression of fatty acid synthase (FAS) gene as well as for insulin and/or carbohydrate-stimulation of this gene, primary hepatocytes were transfected with plasmids containing the 5'-flanking sequence of the rat FAS gene fused to the CAT gene. Sequences from -1604, -88 or -57 to +79 of the FAS gene directed an increase in CAT activity in the hepatocytes when insulin/glucose was added to the medium, in accordance with the responses an the endogenous FAS gene expression. The CAT activities were reduced by the addition of PUFA. Further deletion to -34, however, resulted in loss of the responses. The results suggest that the region from -57 to -34 of the FA gene may be responsible for regulation due to insulin/glucose and PUFAs. Moreover, the region was also reponsible for stimulation due to pyruvate alone.