The effects oftrans fatty acids on fatty acyl Δ5 desaturation by human skin fibroblasts

The effectiveness of different fatty acids as inhibitors of fatty acyl delta 5 desaturation activity in human skin fibroblasts has been investigated. When incubated with 2.25 microM [14C] eicosatrienoate (20:3 omega 6) in otherwise lipid-free medium, these cells rapidly incorporate the radiolabeled fatty acid into cellular glycerolipids and desaturate it to produce both [14C] arachidonate and [14C]docosatetraenoate. The delta 5 desaturation activity can be enhanced by prior growth of the cells without serum lipids. Elaidate (9t-18:1) is a potent inhibitor of delta 5 desaturation while trans-vaccenate (11t-18:1) is virtually without effect. Oleate and linoleate are only mildly inhibitory. Linoelaidate (9t,12t-18:2) is more inhibitory than linoleate but significantly less effective than elaidate. The effects of elaidate can be readily overcome by increasing the concentration of exogenous eicosatrienoate. Studies with a variety of trans monounsaturates of differing chain lengths indicate that the omega 9 trans fatty acids are potent inhibitors of delta 5 desaturation, while omega 7 trans fatty acids are relatively ineffective. Intact human fibroblasts could thus be important in characterizing novel fatty acids as selective inhibitors of arachidonate synthesis in vivo.