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. IntroductionThe 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][3][4][5] On the other hand, lipids produced by keratinocytes are a mixture of almost equal 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 LipidsThe 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][8][9][10][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][13][14] The reason for such a unique sebum composition is not understood; how...

A pilot study was conducted to compare lipid components of sebum from unaffected and acne-affected individuals. Nine males, 15-20 years old, with no acne, or with moderate to severe acne, were recruited. Facial images were taken with regular, polarized and fluorescent lights for each subject. Skin surface lipids were analyzed following collection of sebum using sebutapes. As expected, the subjects with acne had more (59%) sebum than the control subjects. Free fatty acids were the only lipid group that was reduced in the sebum of acne subjects. The specific lipid that differed the most between the two groups was squalene, which was upregulated in acne subjects by 2.2-fold on a quantitative basis. Squalene also represented a significantly greater proportion of the total sebaceous lipids in acne patients compared to controls (20% vs. 15%). The increase in the amount of squalene could represent a lipid marker for acne prone skin.

The sebaceous gland is an integral part of the pilosebaceous unit of mammalian skin, which produces and secretes a unique mixture of lipids, known as sebum. Wax esters, which account for approximately 25% of human sebaceous lipids, are unique in that they are not synthesized by other cells in the body. To explore the biosynthesis of wax esters, the metabolic fate of exogenously supplied saturated (16:0, 18:0), mono-unsaturated Delta9 (16:1, 18:1), and polyunsaturated (18:2, Delta9,12) fatty acids was followed in biopsy punches from human facial skin rich in sebaceous glands. Acetate was incorporated into all of the cellular and secreted lipids and 16:0 was incorporated into all of the fatty-acid-containing lipids. The 16:0 was elongated to 18:0 and the 16:1 was incorporated primarily into polar lipids, secondarily into triglycerides, but not into other lipids and was elongated to 18:1 (Delta11). As proven by HPTLC analysis, both 18:0 and 18:1 were incorporated into the cellular lipids but at a lower rate into wax esters. Moreover, addition of exogenous 18:1 was not further processed following initial incorporation. Linoleic acid (18:2, Delta9,12) was the only fatty acid tested that appeared to be subjected to beta-oxidation. This was proven to be specific to linoleic acid, as it did not induce the oxidation of other fatty acids. The ability of the sebaceous cells to synthesize wax esters correlated with the beta-oxidation activity in these cells. Thus, the oxidation of linoleic acid is specific for the sebaceous cells and correlates with their function and differentiation. Our results provide evidence that the sebaceous gland selectively utilizes fatty acids as 16:0 is the preferred fatty acid that is incorporated into wax esters and linoleic acid undergoes beta-oxidation.

Acne skin demonstrates increased transepidermal water loss (TEWL) compared with healthy skin, which may be due, in part, to altered ceramide (CER) levels. We analysed ceramides in the stratum corneum of healthy and acne skin, and studied seasonal variation over the course of a year. Using ultraperformance liquid chromatography with electrospray ionisation and tandem mass spectrometry (UPLC/ESI-MS/MS), we identified 283 ceramides. Acne-affected skin demonstrated overall lower levels of ceramides, with notable reductions in CER[NH] and CER[AH] ceramides, as well as the acylceramides CER[EOS] and CER[EOH]; these differences were more apparent in the winter months. Lower ceramide levels reflected an increase in TEWL in acne, compared with healthy skin, which partly resolves in the summer. Individual ceramide species with 18-carbon 6-hydroxysphingosine (H) bases (including CER[N(24)H(18)], CER[N(26)H(18)], CER[A(24)H(18)], CER[A(26)H(18)]) were significantly reduced in acne skin, suggesting that CER[NH] and CER[AH] species may be particularly important in a healthy skin barrier.

This study was conducted to compare lipid components of sebum from persons from three ethnic backgrounds—Caucasian, African American and Northern Asian. Men and women with no acne in two age groups (18‒25 y and 35‒45 y) were recruited. Skin surface hydration (SkiCon 200EX and NovaMeter), barrier function (Delfin VapoMeter), high-resolution clinical imaging, self-assessments and two pairs of sebutapes on the forehead that extracted the lipids on the surface of their skin were used. Significant differences (p < 0.05) in skin hydration between African Americans and Caucasians in both age groups were noted, with the order from highest to lowest absolute values: African American > Northern Asian > Caucasian. Transepidermal water loss (TEWL) measurements demonstrated that African Americans and Caucasians were significantly different (p < 0.05), with the trend being the inverse of the hydration trend—Caucasian > Northern Asian > African American, which would indicate better barrier function for African Americans with a lower TEWL. African American women had more total lipid production than Northern Asian or Caucasian women. When analyzing the three lipid classes (free fatty acids, triglycerides and wax esters), the trend became significant (p < 0.05) in the wax ester fraction when directly comparing African Americans with Caucasians. Additionally, six lipids were identified in the wax ester fractions that were significantly different in quantity (p < 0.05) between African Americans and Caucasians. These results identified significant differences in sebaceous lipid profiles across ethnic groups and determined that the differences correlated with skin barrier function.

Activation of peroxisome proliferator-activated receptors (PPARs) has been shown to have an important role in skin barrier function by regulating differentiation and lipid synthesis in keratinocytes. Oat (Avena sativa) has long been used as a soothing agent to relieve skin irritations, and the clinical benefits of topical oat formulations have been proven; however, the mechanistic understanding of oat's mode of action remains unknown. We investigated whether an oat lipid extract could activate PPARs and subsequently increase epidermal lipid synthesis and differentiation markers. Primary human epidermal keratinocytes and transformed cell lines were treated with PPAR agonists and oat lipid extracts to investigate the PPAR agonism. PPAR target genes and epidermal differentiation markers were analysed using quantitative real-time PCR and HPTLC analysis. Oat lipid extract demonstrated robust dual agonism for PPARα and PPARβ/δ, and increased direct PPAR target gene induction in primary human keratinocytes. In addition, oat oil treatment increased both receptor expression and, consistent with the literature on PPARs, oat oil treatment resulted in a significant upregulation of differentiation genes (involucrin, SPRRs and transglutaminase 1) and ceramide processing genes (β-glucocerebrosidase, sphingomyelinases 3 and ABCA12). Further, oat oil treatment in keratinocytes significantly increased ceramide levels (70%), suggesting a functional translation of PPAR activation by oat oil in keratinocytes. Taken together, these results demonstrate that oat lipids possess robust dual agonistic activities for PPARα and PPARβ/δ, increase their gene expression and induce differentiation and ceramide synthesis in keratinocytes, which can collectively improve skin barrier function.

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