INSULIN GLUCOSE-RESPONSIVE, PYRUVATE-RESPONSIVE AND POLYUNSATURATED FATTY ACID-RESPONSIVE REGION(S) OF RAT FATTY-ACID SYNTHASE GENE PROMOTER/

To investigate the regulatory DNA sequences required for polyunsaturat ed fatty acid (PUFA)-suppression of fatty acid synthase (FAS) gene as well as for insulin and/or carbohydrate-stimulation of this gene, prim ary hepatocytes were transfected with plasmids containing the 5'-flank ing 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 medi um, in accordance with the responses an the endogenous FAS gene expres sion. The CAT activities were reduced by the addition of PUFA. Further deletion to -34, however, resulted in loss of the responses. The resu lts suggest that the region from -57 to -34 of the FA gene may be resp onsible for regulation due to insulin/glucose and PUFAs. Moreover, the region was also reponsible for stimulation due to pyruvate alone.