Development and characterization of a tissue culture cell line with essential fatty acid deficiency.

Abstract

An essential fatty acid-deficient cell line was developed from a parental [mouse fibrosarcoma] cell line, HSDM1C1, which metabolizes arachidonic acid to prostaglandin E2 (PGE2). This cell line, designated EFD-1, is depleted of arachidonate, is unable to synthesize PGE2 in response to bradykinin and has changes in fatty acid composition characteristic of tissues from animals with essential fatty acid deficiency. Within 15 min of repletion by arachidonate, the ability to synthesize PGE2 is restored. Linoleate also is able to restore PGE2 synthesis, indicating that deficient cells contain both the rate-limiting .DELTA.6 desaturase enzyme and the .DELTA.5 desaturase enzyme, which are required to form arachidonate. When parental cells are incubated in lipid-free medium, there is rapid induction of the ability to convert linoleate to arachidonate. Arachidonate prevents this induction, suggesting that icosanoid precursor availability controls the rate of arachidonate formation.