Sebaceous gland lipids.

[Dermato-Endocrinology 1:2, 68-71; March/April 2009]; ©2009 Landes Bioscience Special Focus Review Sebaceous gland lipids Mauro Picardo,* Monica Ottaviani, Emanuela Camera and Arianna Mastrofrancesco San Gallicano Dermatological Institute; IRCCS; Rome, Italy Abbreviations: Sq, squalene; PUFAs, polyunsaturated fatty acids; 16:0, palmitic acid; 16:1 Δ6, sapienic acid; 18:2 Δ5,8, sebaleic acid Key words: sebum, squalene peroxide, acne, diet The principal activity of mature sebaceous glands is producing and secreting sebum, which is a complex mixture of lipids. Sebum composition is different among species and this difference is probably due to the function that sebum has to absolve. In human sebum there are unique lipids, such as squalene and wax esters not found anywhere else in the body nor among the epidermal surface lipids. Moreover, they correspond to major components supplying the skin with protection. However, the ultimate role of human sebum, as well the metabolic pathways regulating its composition and secretion rate, are far from a complete understanding. Increased sebum secretion is considered, among all features, the major one involved in the pathophysiology of acne. Along with increased sebum secretion rate, quali- and quantitative modifications of sebum are likely to occur in this pathology. Understanding the factors and mechanisms that regulate sebum production is needed in order to identify new targets that can be addressed to achieve a selective modulation of lipid biosynthesis as a novel therapeutic strategy to correct lipid disregulations in acne and other disorders of the pilosebaceous unit. Sebum The principal activity of mature sebaceous glands is producing and secreting sebum, which is a complex mixture of lipids. This is a holocrine secretion formed by the complete disintegration of glandular cells into the follicular duct of pilosebaceous unit. Sebum discharge represents a major step in the final stages of differentiation of sebaceous specialized cells, namely sebocytes, and it is the result of accumulation of cytoplasmic lipid droplets and subsequent cell disintegration and release of their content into the follicle. Sebum composition is different among species and this difference is probably due to the function that sebum has to absolve. Among the functions attributed to sebum in humans there is photoprotection, antimicrobial activity, delivery of fat-soluble anti-oxidants to the skin surface and pro- and anti-inflammatory activity exerted by specific lipids.1 However, the ultimate role of human sebum, as well *Correspondence to: Mauro Picardo; San Gallicano Dermatological Institute IRCCS; Via Elio Chianesi 53 00144 Rome; Tel.: +39.06.52666257; Fax: +39.06.52666247; Email: Submitted: 01/15/09; Accepted: 03/18/09 Previously published online as a Dermato-Endocrinology E-publication: http://www.landesbioscience.com/journals/dermatoendocrinology/article/8472 68 Table 1 Glycerides FFA WE SQ CE CH Components of skin surface lipids Sebum % Epidermal lipids % 30–50 30–35 15–30 8–16 26–30 - 12–20 - 3.0–6.0 15–20 1.5–2.5 20–25 Glycerides; Free Fatty Acids (FFA); Wax Esters (WE); Squalene (SQ); Cholesterol Esters (CE); Cholesterol (CH). as the metabolic pathways regulating its composition and secretion rate, are far from a complete understanding. Human sebum consists of squalene, esters of glycerol, wax and cholesterol, as well as free cholesterol and fatty acids (Table 1). Triglycerides and fatty acids, taken together, account for the predominant proportion (57.5%), followed by wax esters (26%) and squalene (12%). The least abundant lipid in sebum is cholesterol, which with its esters, accounts for the 4.5% of total lipids.2 The most characteristic products of sebaceous secretion are squalene and wax esters. They are unique to sebum and not found anywhere else in the body nor among the epidermal surface lipids. Moreover, they correspond to major components supplying the skin with protection. Squalene is a linear intermediate preceding cholesterol in its biosynthesis. Interestingly, in the sebaceous gland, the squalene produced is not converted into lanosterol, halting the completion of the biosynthetic pathway leading to cholesterol. The reason cholesterol is not synthesized in the sebaceous gland, favoring squalene accumulation, is still unclear. Possible explanation for the squalene buildup in the sebaceous gland may be linked to an overexpression or an increase in the activity of squalene-synthase in the cells; or it may be related to decreased level or activity of the enzymes involved in the conversion to cholesterol.3 In addition, taking into account the peculiarity of squalene, it may be considered as a marker for sebocytes differentiation and thus for sebogenesis.4 Other features unique to sebum are the branched chain fatty acids and lipids with particular pattern of unsaturation. The Δ6 desaturase enzyme (fatty acid desaturase-2) catalyzes a “sebaceous-type” reaction of desaturation that leads to particular compounds.5 It is the major desaturase found in the sebaceous gland, and it is detectable mainly in differentiated sebocytes, which occupy the suprabasal layers of the sebaceous gland and have Dermato-Endocrinology 2009; Vol. 1 Issue 2 Sebaceous gland lipids reached a full lipid synthetic capacity, providing a functional marker of activity and differentiation of sebocytes.5 Δ6 desaturase preferentially converts palmitic acid (16:0) to sapienic acid (16:1, Δ6), which is unique to the human sebum and represents ca. 25% of the total fatty acids. Elongation of sapienic acid by 2-carbon unit and further unsaturation leads to the formation of sebaleic acid (18:2, Δ5,8), which is also peculiar of human sebum. The ratio between Δ6 and Δ9 unsaturated fatty acids has been proposed as an index of maturation of sebaceous cells and of metabolic process associated to it.6 Sebum Alterations in Acne Acne vulgaris is a disease of the pilosebaceous unit resulting from the interplay of different factors: seborrhoea, P. acnes colonization, hyperkeratinization of the follicular duct and release of inflammatory mediators. Increased sebum secretion is considered, among all features, the major one involved in the pathophysiology of acne. On average, acne subjects excrete more sebum than normal ones and secretion rates correlate well with the severity of clinical manifestations.7 Along with increased sebum secretion rate, quali- and quantitative modifications of sebum are likely to occur. Decreased concentration of linoleic acid has been observed in skin surface lipids of acne patients. In particular, its level has been found significantly reduced in wax esters making it reasonable to assume that linoleic acid is directly involved in the sebaceous lipid synthesis.8 Moreover, experimental data suggest that it is incorporated in epidermal lipids of the infundibulum. In experimental models, linoleic acid is preferentially transformed into two (...truncated)