Essential fatty acids in epidermal barrier function

Abstract

A deficiency of linoleic acid results in increased transepidernial water loss and leads to empty or only partially filled lamellar bodies. HFA deficiency in mammalian and human skin is characterized by increased transepidernial water loss, scaliness, an increased mitotic index indicating hyperproliferalion and inflammation. In EFA deficient epidemiis linoleyl-glucosyl-ceramides are found to be substituted by oleic acid in the ester-linked position. The linoleate moiety in acylglucosylceramides play a critical role for the assembly of lamellar bodies. The acylceramides, especially linoleyl-ceramides, exert their function in riveting together the adjacent bilayers found in the intercellular space of the horny layer. EFA deficient hairless mice with defective barrier function reveal a twofold increase in epidermal cholesterol synthesis. Epidermal slerologenesis in EFA deficient animals, repleted with linoleic acid either systemically or topically, relumed toward normal as barrier function improved. Moreover, EFA deficency induced serine palmitoyl transferase activity, the rate-limiting enzyme in sphingolipid synthesis. In EFA deficient animals epidermal DNA synthesis increased 50% suggesting that an appropriate amount of EFAs is important for epidermal barrier function and regulation of epidermal DNA synthesis. Epidermal EFA metabolism is disturbed in atopic dry skin. In atopic xerosis we could demonstrate a deficiency of the total amount of stratum corneum ceramides. Recently, it could be shown that among the ceramidc fractions, the decrease of the linoleale-eslerified ceramide 1, which is considered an essential component of the barrier function, was most prominent. Thus, EFAs play an important role in epidermal barrier function. A deficiency of EFAs leads to functional and structural defects in the formation of the multilamellar membranes of stratum corneum and lamellar bodies and affects epidermal sterologcnesis, sphingolipid as well as epidermal DNA synthesis.