The ultimate objectives are to discover the role of lipids in epidermal structure and function and to determine to what extent any of the common disorders of keratinization in human skin can be attributed to faulty epidermal lipid metabolism. Certain linoleate-rich lipids of mammalian epidermis have been shown to have unique structures that have been postulated as having specific roles in assembly of the lipid bilayers present in epidermal lamellar granules and in the intercellular spaces of the stratum corneum. The mechanism of this assembly will be investigated by studying the effects of these lipids on synthetic lipid bilayers in vitro. Effects on the morphology of the bilayers will be examined by electron microscopy and by nuclear magnetic resonance spectroscopy. These effects will be compared with those produced by specific polar lipids obtained from essential fatty acid deficient pigs, by certain novel polar lipids from avian and reptilian skin, and by synthetic analogs of the epidermal polar lipids. Changes in epidermal lipid linoleate content that we have shown to accompany post-natal development in mammals provide an opportunity to correlate linoleate level with epidermal function and ultrastructural morphology in grossly normal skin. Acylceramide and acylglucosylceramide will be isolated from the epidermis of pigs of known age and examined for the composition of their esterified fatty acids. Water permeability of epidermis of the same animals will be measured in vivo and skin specimens will be examined for ultrastructural morphology and proliferation rate. Other young pigs will be raised on diets containing specific fatty acid compositions to determine whether the natural epidermal linoleate content results from availability of this essential fatty acid or from inherent control of the linoleate content in the epidermal polar lipids. Topical application of specific triglycerides will determine to what extent the epidermal polar lipid composition can be influenced by this route. Pathways of polar epidermal lipid metabolism will be investigated in primary keratinocyte cultures maintained under conditions adjusted to allow normal lipid metabolism. Radiolabelled precursors of the polar lipids, including linoleate, glucose, serine and acetate, will be used to identify the metabolic pathways. Cultures of keratinocytes will be subjected to essential fatty acid deficiency, to high levels of specific fatty acids, and to synthetic retinoids, to eludicate their lipid metabolism.
Showing the most recent 10 out of 43 publications
