Epidermal surface lipids.

[Dermato-Endocrinology 1:2, 72-76; March/April 2009]; ©2009 Landes Bioscience Special Focus Review Epidermal surface lipids Apostolos Pappas The Johnson & Johnson Skin Research Center; CPPW, a Division of Johnson & Johnson Consumer Companies, Inc.; Skillman, New Jersey USA Abbreviations: SC, stratum corneum; KO, knock out; VLCFA, very long chain fatty acids Key words: lipid, sebaceous, skin, fatty acid, desaturase, wax, squalene, ceramide A layer of lipids, which are of both sebaceous and keratinocyte origin, covers the surface of the skin. The apparent composition of surface lipids varies depending on the selected method of sampling. Lipids produced by the epidermal cells are an insignificant fraction of the total extractable surface lipid on areas rich in sebaceous glands. Due to the holocrine activity of the sebaceous gland, its product of secretion (sebum) is eventually released to the surface of the skin and coats the fur as well. Lipids of epidermal origin fill the spaces between the cells, like mortar or cement. The sebaceous lipids are primarily non polar lipids as triglycerides, wax esters and squalene, while epidermal lipids are a mixture of ceramides, free fatty acids and cholesterol. The composition of the sebaceous lipids is unique and intriguing and elevated sebum excretion is a major factor involved in the pathophysiology of acne. Recent studies have elucidated the roles that epidermal surface lipids have on normal skin functions and acne. Introduction The sebaceous gland is now considered to be an important endocrine organ. The holocrine eruption of the sebaceous cells results in the secretion and release of sebum, which eventually coats the surface of the skin and the fur. The majority of the epidermal surface lipids are in fact of sebaceous origin while the lipids produced by the epidermis are an insignificant fraction of the total extractable surface lipid.1 That is more apparent on areas rich in sebaceous glands, where the epidermal origin lipids average between 5 to 10 μg per sq cm, compared with average recoveries of 150 to 300 μg of sebum per sq cm from the forehead. Since this chapter is part of a sebaceous forum, the focus will include both classes of lipids on the surface of the skin. In addition, areas rich in sebaceous glands are the areas that acne lesions are manifested. Human sebum is a mixture of non-polar lipids, mainly triglycerides, wax esters, squalene, fatty acids and smaller amounts of cholesterol, cholesterol esters and diglycerides.2-5 On the other hand, lipids produced by keratinocytes are a mixture of almost equal Correspondence to: Apostolos Pappas; The Johnson & Johnson Skin Research Center; CPPW, a Division of Johnson & Johnson Consumer Companies, Inc.; Skillman, New Jersey 08558 USA; Email: Submitted: 01/09/09; Accepted: 01/12/09 Previously published online as a Dermato-Endocrinology E-publication: http://www.landesbioscience.com/journals/dermatoendocrinology/article/7811 72 proportions of free fatty acids, cholesterol and ceramides.6 Figure 1 shows the representative structures of the various lipid classes of epidermal surface lipids. Sebaceous Lipids The sebaceous lipids are unique and intriguing. According to Nicolaides:7 “two key words characterize the uniqueness of skin lipids: complexity and perversity”. The relative composition of sebum depends on the sampling method used. In particular, if the major components of sebum, triglycerides, are sampled before or after their modification by bacteria, which hydrolyze them to free fatty acids and glycerol.7-11 The mean weight % that is often cited in the literature is given in Table 1. Interestingly, human sebaceous lipids are significantly different in quantity and quality from sebaceous lipids of other species.12-14 The reason for such a unique sebum composition is not understood; however, one can also consider that human skin has a unique texture. In addition, acne is also unique to humans. These seem to be pieces of the same puzzle, which suggest that the unique sebaceous lipids are associated to this odd and human specific disease. Elevated sebum excretion is clearly a major factor involved in the pathophysiology of acne.15-17 Although the majority of lipids produced by all other organs of the human body are alike, the sebaceous gland produces some unique species that cannot be found in any other organ of the body. The synthesis of sapienic acid or wax esters, the accumulation of squalene and the presence of very long chain branched or hydroxylated fatty acids are uncommon in other organs and unique manifestations in sebum.7,12 In other mammals and rodents even higher levels of unique fatty acids exist and with either odd numbers of carbon atoms or branched chains. It is also possible that some of these molecules are in reality products of the resident skin micro flora, since they are more common to bacterial metabolism.18 However, another possibility is that they could be synthesized from branched precursors, products of essential branched amino acid catabolism.4 Sapienic acid. The predominant fatty acid of sebum is the sapienic acid (16:1, Δ6), which has its single double bond at the sixth position from the carboxyl end.7,19 In nature, long chain fatty acids with similar chain length are abundant but there is a predominant preference for the first double bond to be inserted in the 9th position from the carboxyl end. The 16-carbon isomer with one double bond at the ninth position is the palmitoleic acid, which is naturally Dermato-Endocrinology 2009; Vol. 1 Issue 2 Epidermal surface lipids Figure 1. Representative structures of epidermal surface lipids. found in many tissues and organisms. Sapienic acid is truly unique to sebum and is not found anywhere else in the human body. In addition, humans do not obtain it from the diet since very few plant species have been reported to manufacture this unusual fatty acid.7,18 The elongation of sapienic acid by two carbons and then an additional insertion of another double bond between the fifth and sixth carbon yields sebaleic acid (18:2Δ5, 8), a reaction and metabolite that occurs only in human sebaceous cells. The levels of sapienic acid are multiple folds higher than any of its derivatives, isomers or other monounsaturated fatty acids found in sebum. However, the potential role of sapienic acid in the etiology of acne is still controversial. It has been argued that its presence in sebum correlates with elevated sebum levels,20 while others report that it can be potent against bacteria commonly associated with acne.21-23 Wax esters. Wax esters are also unique to sebaceous cells and are not produced by any other cell in the body. They account for about 25% of the sebaceous gland lipids and their production correlates with sebaceous gland differentiation.5,19 Animal models demonstrated a strong correlation between atrophic sebaceous gland and impaired wax ester synthesis.24,25 Wax ester synthases26,27 have recent (...truncated)