Lipidomics in stratum corneum research
Research Article
Lipidomics analysis of stratum corneum is essential in dermatology research and product development.
Summary
Resources
Large-scale human skin lipidomics…
Sadowski et al. | Sci. Rep (2017)
Changes in levels of omega-O-acylceramides…
Rawlings et al. | IJCS (2022)
Evaluation of a novel skin emollient cream…
Jacques et al. | Skin Pharmacol Physiol (2023)
Alteration of barrier properties…
Murphy et al. | Sci. Rep (2022)
An automated shotgun lipidomics platform…
Surma et al. | EJLT (2015)
Systematic screening for novel lipids by…
Papan et al. | Anal. Chem. (2014)
THE human skin serves as the outer protective covering of the body and holds the distinction of being the largest organ within the integumentary system. Beyond its physical barrier, the skin also plays a vital role in the immune system, safeguarding the body against harmful pathogens and preventing excessive water loss. Moreover, the skin fulfills multiple functions, including insulation, temperature regulation, sensation, synthesis of vitamin D, and protection of folate stores.
Keratinocytes represent the primary type of cells found in the epidermis. These cells originate from epidermal stem cells located in the lower part of the epidermis (stratum basale). As they mature, keratinocytes undergo a process of differentiation and migrate upward through the spinous and granular layers (stratum granulosum) of the epidermis, finally reaching the outermost layer called the cornified layer (stratum corneum). In the stratum corneum, the keratinocytes fully transform into corneocytes, which are tough, flattened cells that make up the protective barrier of the skin. Eventually, these corneocytes are shed off from the skin’s surface through the natural process of exfoliation.
Within human populations, skin pigmentation exhibits variability, and skin types can range from dry to non-dry and from oily to non-oily. In addition to inter-individual variability, high intra-individual variability of skin moisture and structure is observed. This variability depends on the body area within the same individual. Such diversity in skin characteristics provides a rich and varied habitat for the microbiome – the community of microorganisms that reside on the skin’s surface. In this article we will discuss some aspects of lipidome variability in human stratum corneum health and pathology.
Variability of skin lipidomics profiles
Stratum corneum structure is analogous to a ‘brick-and-mortar’ structure. A lipid matrix is characterized by stacked lipid lamellae forming a highly organized, three-dimensional configuration. The stratum corneum lipids display lateral arrangements that may take the form of liquid, hexagonal, or orthorhombic phases. Main stratum corneum lipids are ceramides, cholesterol, free fatty acids, triglycerides, diglycerides, and cholesteryl esters.
The composition of stratum corneum lipids is recognized to be subject to variations influenced by factors such as skin pigmentation, age, gender, seasonal changes, and specific skin conditions. Although these connections have not been fully elucidated, they are believed to have potential effects on the skin’s barrier function.
Skin tape stripping as a non-invasive method for skin sampling: Tape stripping for skin sampling involves the application of a specialized adhesive tape disc onto a specific area of the body. After a brief period of pressure, the tape is removed, with the skin adhering to it. This process allows for the extraction of sebum lipids and stratum corneum lipids, which can be subsequently analyzed in lipidomics studies. Applying multiple tapes to the same spot at once enables quick triplicate sampling, while sequential tape stripping permits an analysis of skin depth.
The predominant lipids in the stratum corneum lipidome consist of ceramides, cholesterol, and free fatty acids. Additionally, triglycerides, diglycerides, and cholesteryl esters (another type of cholesterol lipid) are commonly present in the skin. Ceramide lipids, which comprise a sphingoid base linked to a fatty acid, play a vital role in maintaining skin hydration. Variations in the relative abundance of 12 ceramide subclasses in the skin have been associated with conditions of excessive oiliness or dryness. Consequently, ceramides are of great interest to researchers involved in the development of skin moisturizers. The specific functions of other lipid classes in skin barrier function are still the subject of ongoing investigation.
To bridge this knowledge gap, a joint research effort involving scientists from Lipotype and the University of Medicine in Wrocław, Poland conducted a comprehensive study. This study employed mass spectrometry-based lipidomics to characterize the lipid profile in stratum corneum samples obtained from 104 individuals. The findings shed light on the variations in the skin lipidome, including variations in relation to skin depth, within individual subjects, and among different individuals depending on their sex and age.
Impact of sampling depth on skin lipid composition: Lipidomics analysis of stratum corneum tape strips from female and male subjects. Drawn-through lines represent female skin lipid profiles, dashed lines represent male skin lipid profiles. A Means of total amounts of lipids measured in females and males at different age. B Lipid profiles of lipid classes of females and males of different age.
Sadowski et al., Sci Rep (2017), doi: 10.1038/srep43761
This research underscores the significance of skin depth, location, age, and gender in shaping the dynamic property of the skin lipid profile, which in turn can influence the function of this organ. Nevertheless, the precise impact of this variability, both between individuals and within the same person, on skin barrier function remains to be fully understood. Future studies utilizing lipidomics may provide valuable insights into these relationships. The outcomes of such research could potentially serve as biomarkers for assessing health and disease and offer valuable guidance for the advancement of skin care product research and development.
Skin pigmentation and ceramide content
It is essential for skin care research to understand the intricate composition and structure of diverse skin types and pigmentation variations. This knowledge allows for the development of various targeted skin care products such as moisturizers. Moisturizers aimed at effectively preserving transepidermal water loss (TEWL) and maintaining optimal skin hydration. Ceramides is a main lipid class that stands out as a focal point of interest in this research, given its significant impact on the functional integrity of the stratum corneum.
The lipid matrix, along with its specific ceramide lipid profile, plays a pivotal role in preserving skin hydration and regulating TEWL. The field of skin lipidomics analysis has yielded valuable insights into the ceramide composition of the stratum corneum, offering distinct findings that can inform the development of more effective moisturizers tailored to specific skin types and pigmentation.
In a study conducted by DSM, researchers examined the ceramide composition of facial skin in individuals with Albino African, Black African, and Caucasian backgrounds. This research aimed to gain a deeper understanding of how these specific ceramide profiles vary across different skin types, ultimately contributing to the advancement of skin care products designed to cater to the unique needs of diverse populations.
Total ceramide levels for different groups of participants. Different ceramide levels on cheek for Albino African, Black African, and Caucasian study participants. Data are mean ±SEM. * p < 0.05
Rawlings et al., Int J of Cosmet Sci (2022), doi.org/10.1111/ics.12765
The ceramide lipidomics analysis of skin with different pigmentation showed interesting results. Despite an overall higher content of ceramide lipids in Albino African skin samples, a counterintuitive increase in TEWL was observed. This discrepancy is noteworthy because ceramides play a crucial role in preserving water within the lipid matrix that resides between corneocytes. In particular, the ceramides subclasses EOdS, EOS, EOH, AH, NS, NH, and AS exhibited elevated absolute concentrations in comparison to other skin types. Additionally, an increase in immature corneocytes was noted. These changes collectively contribute to heightened TEWL, a compromised skin barrier function, and reduced skin hydration.
These findings underscore the critical role of lipid biochemistry and lipidomics in skin care research and product development. They emphasize that a deep understanding of the molecular aspects of stratum corneum lipids is essential for designing effective skincare solutions tailored to the unique needs of various populations.
Moisturizing cream impacts ceramides balance in skin
When evaluating skin permeability, the quantitative variations in lipid content emerge as a more prominent factor compared to other elements, such as the thickness of the stratum corneum. Researchers have noted that changes in the distribution of ceramide chain length and the ceramide ratio are closely associated with shifts in stratum corneum organization, skin barrier functionality, and the development of skin conditions such as atopic dermatitis, psoriasis, and xerosis.
Jacques and colleagues investigated the barrier-repairing effects of petrolatum on delipidized stratum corneum. Additionally, they examined the impact of repeated topical application of an emollient cream containing glycerol and petrolatum on the composition of ceramide subclasses within a stratum corneum model.
Following the topical application of the moisturizer cream to the skin, an increase in the quantities of EOdS, EOP, and EOS acyl-ceramides was observed in the stratum corneum of the experimental group compared to the control one. Interestingly, the levels of EOP were lower than those of EOS. This discrepancy in ceramide levels, particularly the reduced EOS, can lead to alterations in the structure of the epidermal barrier, resulting in increased moisture loss and heightened skin permeability.
The reduction in acyl-ceramides contributes to the damaged skin barrier detected in skin conditions such as atopic dermatitis and ichthyoses. These conditions are characterized by disruptions in the skin’s protective barrier, leading to increased susceptibility to moisture loss, environmental irritants, and a range of related skin issues.
Acyl-ceramide quantities in control and stratum corneum model treated with the moisturizer cream. EodS, EOH, EOP, and EOS Values are mean ± SEM are shown; n = 18; **, p ≤ 0.01.
Jacques et al., Skin Pharmacol Physiol (2023) 36 (3): 125–139, 10.1159/000529253
In summary, the examined moisturizer cream exhibited enhanced ceramide content and reinforced the skin’s barrier function. The effectiveness of the cream can be attributed to its semi-occlusive properties, acting as an additional protective layer. Significantly, the cream was found to penetrate the stratum corneum without causing any structural compromise. This analyzed cream holds potential as a treatment option for individuals with compromised barrier function, including those dealing with conditions like atopic dermatitis and dry skin.
Lipid metabolism & microbiome of dry skin
Xerosis, commonly known as dry skin, affects approximately one-third of the global population, leading to symptoms like itching, irritation, and cracking or peeling. Both the microbiome and the lipid composition must be analyzed to assess the impact of a body lotion on dry skin.
Murphy and Mayes studied the alterations in skin barrier functions, dryness, cohesivity, changes in dry skin lipids, and the skin microbiome both before and after the application of a moisturizing cream containing ingredients such as glycerol, free fatty acids (FFAs), and a limited number of occlusive agents. Study participants underwent initial examinations to establish a baseline before applying the body lotion, and a follow-up assessment was conducted five weeks after consistent use of the body lotion.
Following the intervention, the assessment of skin hydration status, as measured by a corneometer, revealed a significant improvement, along with enhanced cohesivity. Additionally, alterations in the composition of stratum corneum lipids were examined by analyzing the cholesterol, ceramides, and free fatty acid profiles using tape strips taken from the study participants.
The total ceramide level in stratum corneum increased from 2.85 to 3.80 pmol/ug following the intervention. The assessment covered a total of 358 ceramide species, which were categorized into 12 classes. Remarkably, the intervention led to a significant increase in 9 out of the 12 ceramide classes.
Changes of total ceramides level prior and post intervention, measured in 20 strips: A Total level of ceramides increased after the body lotion application for 5 weeks. B Changes in each ceramide subclass: A significant increase upon the body lotion treatment was detected in AdS**, AH**, AP**, AS**, EOH***, EOS*, NH**, NP*, and NS** ceramide subclasses. *, P < 0.05; **, P < 0.01; ***, P < 0.001.
Murphy, et al. Sci Rep 12, 5223 (2022). 10.1038/s41598-022-09231-8
In the final analysis, the examination of the dry skin microbiome both before and after the intervention did not reveal any major alterations following the treatment. Generally, measuring changes in the skin microbiome can be challenging due to the considerable inter-individual variation, especially concerning less dominant microbial community members.
This study delved into the composition of dry skin lipids and the skin microbiome, assessing their changes in response to the application of a moisturizing body lotion. The stratum corneum‘s lipid barrier experienced modifications in ceramides, free fatty acids (FFAs), and cholesterol composition as a result of the treatment, ultimately leading to an increase in hydration levels. The study also detected changes in stratum corneum lipid biosynthesis pathways, such as oleate, palmitate, stearate, and others. The findings of this study provide quantifiable insights into the impact of lotions on both the skin microbiome and the skin lipid profiles.
How to use lipidomics in stratum corneum research and skin product development?
Lipidomics analysis of stratum corneum is essential in dermatology research and product development. The ceramides, a major lipid class in the stratum corneum, play an important in skin hydration and barrier function. That is why it is important to take a closer look at ceramide subclasses when working on moisturizer development, especially in the case of targeting groups of various skin pigmentation, age, gender, and skin conditions.
Lipotype Skin Lipidomics technology is a valuable tool for characterizing the lipidome of the skin using small, non-invasive sample collections. This technology enables researchers to obtain data on lipid abundance and composition. These lipid profiles can be highly informative for researchers investigating how various factors, such as drugs, environmental influences, the microbiome, cosmetics, and other factors that impact and modulate skin function.
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