The long term aim of this proposal is to establish improved methods for the treatment or prevention of acne. The primary hypothesis in these studies is that comedo format results from a deficiency of linoleate that is localized in the epithelium of the pilo- sebaceous follicle. Such deficiency may arise by dilution of sebocyte linoleate according to the quantity of sebum synthesized by each cell. As a corollary, it is propose that the linoleate- deficient sebaceous lipids, especially the free fatty acids, percolate through the follicular horny layer and impose a deficiency of linoleate on the fatty acids that are incorporated as esters in the epithelial acylceramide and acylglucosylceramide. Consequent hyperkeratinization and decreased barrier function, that are characteristic responses of epidermis to EFA deficiency, would lead to comedo formation. Subsequent increase in the population of follicular bacteria may be responsible for the development of the inflammatory lesions of acne. For investigation of these processes, it is proposed to study the role of elevated sebum secretion on the generation of linoleate- deficient sebum and the effect of such sebum on epidermal ceramide composition and comedo formation. Further insight will b sought by investigation of the possible role of diet in avoiding linoleate-deficient epidermal lipids and the development of acne. In attempts to alleviate acne by dietary means, effects on the pathologic condition will be evaluated both by clinical results and by changes in composition of sebum and epidermal lipids. Sebum will be collected in bentonite clay from defined areas on the forehead and analyzed and quantified by thin layer chromatography. Sebum secretion rate per follicle will be calculated from the numbers of follicles per unit area and estimates of sebum secretion per sebocyte will be based on sebum composition. These methods will be use to study the changes in sebum secretion and composition that occur during puberty, at which time comedo formation is initiated, and in the period following physical maturity, when acne usually recedes. In the same subjects, the composition of the epidermal acylceramides will be studied to assess the manifestation of linoleate deficiency in these lipids that are intimately involved in epidermal differentiation and barrier function. Similar analyses will be made of sebum and epidermal lipids in subjects with inflammatory acne, in those undergoing standard treatments for acne, and in populations attempting alleviation of their acne by increasing their dietary linoleate.
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| Stewart, M E; Steele, W A; Downing, D T (1989) Changes in the relative amounts of endogenous and exogenous fatty acids in sebaceous lipids during early adolescence. J Invest Dermatol 92:371-8 |
| Strauss, J S; Davey, W P; Denton, S J et al. (1988) Effect of an orally administered arotinoid, Ro 15-0778, on sebum production in man. Arch Dermatol Res 280:152-4 |
| Perisho, K; Wertz, P W; Madison, K C et al. (1988) Fatty acids of acylceramides from comedones and from the skin surface of acne patients and control subjects. J Invest Dermatol 90:350-3 |
