Cutaneous permeability barrier disruption increases fatty acid synthetic enzyme activity in the epidermis of hairless mice.

Previous studies have shown that abrogation of the cutaneous permeability barrier stimulates epidermal fatty acid synthesis and that this increase is required for barrier repair. The purpose of the present study was to determine the enzymatic basis for this increase in synthesis. Acute barrier disruption by tape stripping increased both acetyl CoA carboxylase (62%) and fatty acid synthase (54%) activities in the epidermis. Similarly, acute disruption of the barrier by topical acetone treatment increased epidermal acetyl CoA carboxylase (69%) and fatty acid synthase (43%) activities. In both acute models, provision of an artificial barrier by occlusion with an impermeable membrane prevented the increase in acetyl CoA carboxylase and fatty acid synthase activities, indicating that the increased activity was dependent on an increase in transepidermal water loss and cannot be attributed to nonspecific effects. In addition, chronic disruption of the barrier, produced by feeding an essential-fatty-acid-deficient diet, also increased acetyl CoA carboxylase (127%) and fatty acid synthase (49%) activities in the epidermis. Again, occlusion with an impermeable membrane decreased both acetyl CoA carboxylase and fatty acid synthase activities toward normal. These results indicate that the increase in fatty acid synthesis that occurs in the epidermis after barrier disruption is due to a coordinate increase in the activities of both epidermal acetyl CoA carboxylase and fatty acid synthase.