Skin, the body's largest organ, serves as a protective barrier against external threats and plays a crucial role in maintaining overall health. Among the myriad components that contribute to skin function, lipids stand out as key players.
Types of Skin Lipids
Skin lipids encompass a wide array of molecules, each with its unique role in skin health. Some of the prominent types of lipids found in the skin include:
- Ceramides: These sphingolipids are vital for maintaining the structural integrity of the skin barrier, preventing moisture loss and protecting against external irritants.
- Fatty acids: Essential components of sebum, fatty acids lubricate the skin surface, keeping it supple and hydrated. They also exhibit antimicrobial properties, helping to fend off pathogens.
- Cholesterol: While often associated with cardiovascular health, cholesterol is also abundant in the skin and contributes to barrier function by regulating membrane fluidity and stability.
- Phospholipids: These amphiphilic molecules play a crucial role in forming lipid bilayers, which constitute the basis of cell membranes, further enhancing skin barrier function.
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Functions of Skin Lipids
The intricate interplay of various skin lipids orchestrates several vital functions essential for healthy skin:
- Maintaining skin barrier integrity: Ceramides, in particular, play a central role in forming the lamellar structure of the stratum corneum, fortifying the skin barrier and preventing transepidermal water loss (TEWL).
- Hydration: Fatty acids and cholesterol contribute to the lipid matrix of the skin barrier, creating a hydrophobic environment that helps retain moisture within the skin layers.
- Immune response: Certain lipids, such as sphingosine-1-phosphate (S1P), serve as signaling molecules involved in regulating immune cell trafficking and inflammatory responses, thereby modulating the skin's immune defense mechanisms.
Significance of Lipid Composition in Skin Conditions
The composition and balance of skin lipids play a pivotal role in various dermatological conditions:
- Dry skin: Deficiencies in ceramides and other lipids can compromise the skin barrier, leading to increased water loss and dryness, a common manifestation in conditions like eczema and xerosis.
- Acne: Dysregulation of sebum production, predominantly composed of triglycerides and fatty acids, contributes to the development of acne vulgaris, highlighting the importance of lipid homeostasis in acne pathogenesis.
- Atopic dermatitis: Alterations in ceramide profiles have been implicated in atopic dermatitis, underscoring the critical role of ceramides in maintaining barrier function and mitigating inflammatory skin disorders.
Application of Lipidomics in Acne
Acne is a chronic inflammatory skin condition linked to the hair follicle and sebaceous gland units, with its development heavily influenced by increased sebum secretion due to androgen stimulation. A significant factor in the onset of acne is the alteration of lipid components within the skin. Studies utilizing advanced lipid analysis techniques have shown that in individuals with acne, there is a notable increase in the total lipid content and significant differences in the composition of these lipids. For instance, the levels of squalene, diglycerides, and wax esters are significantly higher, whereas linoleic acid shows a marked decrease. This information lays a foundational understanding for the mechanisms behind neonatal acne.
Further investigations have explored the relationship between the composition of skin surface lipids and the severity of acne, revealing that the chain length of unsaturated fatty acids decreases with more severe acne cases. Additionally, the severity of acne lesions correlates with increased levels of triglycerides, particularly in adolescent acne. These findings through lipidomics analysis have illuminated the variations in sebum components across different acne severities, providing theoretical insights into the role of sebum alteration in acne pathogenesis and aiding in the development of graded treatment strategies.
Recent studies have also uncovered a connection between acne and dietary lipids. It has been discussed how diet influences acne through aspects such as metabolomics, inflammation, and comedogenesis. High levels of free palmitic acid in the diet can trigger inflammatory processes through the activation of specific inflammatory pathways, while oleic acid has been linked to the stimulation of acne-causing bacteria, keratinocyte proliferation, and the formation of comedones. Therefore, it is suggested that individuals with acne adjust their diet to limit intake of refined carbohydrates, milk, saturated and unsaturated fats, and instead focus on consuming vegetables and fish. Evidence supports that dietary supplementation with omega-3 fatty acids can not only significantly improve acne inflammation but also help alleviate symptoms of other inflammatory skin conditions.
By examining the differences in lipid metabolism between individuals with acne and healthy populations, we can further identify lipid-based interventions for preventing and aiding in the treatment of acne. This approach could also provide precise dietary recommendations for patients, ultimately improving patient satisfaction with acne treatment outcomes.
Application of Lipidomics in Psoriasis
Psoriasis is characterized by the abnormal activation of Th17 cells, playing a crucial role in the disease's pathology through the IL-23/IL-17 axis. A growing body of evidence suggests a close relationship between metabolic pathways and Th17 cell activation. Psoriasis often co-occurs with metabolic-related diseases such as obesity, dyslipidemia, and type 2 diabetes, indicating a link to lipid metabolism dysregulation. Studies, like those conducted by Zeng et al., utilizing ultra-high-performance liquid chromatography-tandem quadrupole mass spectrometry, have compared lipid metabolites in the plasma of psoriasis patients with healthy individuals. These studies found significant increases in glycerophospholipid metabolism, including lysophosphatidic acid and lysophosphatidylcholine, and a decrease in phosphatidylinositol and phosphatidylcholine levels. Additionally, abnormalities in ceramide metabolism, crucial for skin barrier function and immune regulation, have been linked to psoriasis. Research indicates that ceramide synthesis and SPT protein expression levels are significantly lower in psoriatic lesions compared to non-lesioned skin. Luczaj et al. identified differences in ceramide (CER) subtypes within keratinocytes of psoriasis patients, suggesting lipidomics analysis could offer new directions in understanding the link between lipid metabolism variations and T cell activation in psoriasis pathology.
Application of Lipidomics in Vitiligo
Vitiligo is associated with autoimmune destruction of melanocytes, influenced by genetic predisposition and factors like oxidative stress. Research indicates a connection between vitiligo and lipid metabolism abnormalities. Studies, such as those by Kanchan et al., have shown significant differences in lipid profiles of vitiligo patients, including increased LDL-cholesterol and decreased HDL-cholesterol levels. Liang et al. identified 22 lipid species differentially expressed between vitiligo patients and healthy individuals, observing upregulation in lysophosphatidylcholine, sn-glycero-3-phosphocholine, and lipid mediator platelet-activating factor levels. Ye et al. analyzed serum fatty acid levels in vitiligo patients, finding increased α-linolenic acid (ALA) and decreased arachidonic acid (ARA) levels. Additionally, ARA was found to inhibit CD8+ T cell activity, suggesting ARA's potential in blocking the pathogenic process of epidermal melanocyte destruction by suppressing CD8+ T cell activity. This presents a novel direction for vitiligo treatment, highlighting the role of lipid metabolism in the disease's pathogenesis and therapy.
Application of Lipidomics in Systemic Lupus Erythematosus (SLE)
Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease characterized by multi-organ damage. Studies have shown that the pathogenesis of SLE is associated with alterations in lipid metabolism. Metabolic syndrome, manifested by central obesity, hyperglycemia, dyslipidemia, etc., is closely related to the occurrence and development of SLE. Obesity itself induces a pro-inflammatory state, with increased expression of pro-inflammatory molecules such as IL-17, IL-23, and TNF-α. SLE can also cause significant dyslipidemia. Lu et al. identified significant changes in diacyl phosphatidylethanolamine and ceramide components in the lipid profiles of SLE patients using shotgun lipidomics technology, suggesting that these alterations could serve as additional biomarkers for early diagnosis and prognosis of SLE.
Application of Lipidomics in Melanoma
The onset of skin melanoma is often associated with genetic predisposition, prolonged exposure to ultraviolet radiation, and skin damage. However, during tumor development, specific metabolic processes occur. Monitoring changes or fluctuations in metabolites using metabolomics technology may help elucidate the pathogenesis of tumors and identify biomarkers for early diagnosis. Melanoma cells typically metastasize locally through the lymphatic system and then spread through the bloodstream. The exact cause of this metastasis remains unclear. Ubellacker et al. revealed this metastatic mechanism using lipidomics and metabolomics technologies: the lymphatic system has higher levels of oleic acid and reduced glutathione levels, providing cancer cells with higher antioxidant capacity and increasing their survival during subsequent blood-borne metastasis. Perez-Valle et al. compared the lipid profiles of human normal epidermis, melanocytic nevi cells, and malignant melanoma using UHPLC-ESI mass spectrometry. They found that tumor and non-tumor melanocytic cells have distinct lipid features: malignant melanoma cells exhibit elevated levels of ether lipids, phosphatidylglycerol, and phosphatidylinositol, as well as decreased levels of sphingomyelins, highlighting the importance of changes in melanoma cell lipid profiles for distinguishing between benign and malignant melanocytic lesions.
These findings underscore the significance of lipid metabolism in the pathogenesis of systemic lupus erythematosus and melanoma, providing insights into potential diagnostic and therapeutic targets for these conditions.
Application of Lipidomics in Atopic Dermatitis
The skin barrier-itch vicious cycle is a key factor in the pathogenesis of atopic dermatitis (AD), with epidermal lipids playing a crucial role in maintaining normal skin barrier function. Li et al. compared the lipid composition of the stratum corneum between AD patients and healthy controls using LC-MS and explored the relationship between Staphylococcus aureus colonization and skin lipid composition. They found that ceramide (CER) levels, particularly those of Cer[AH], Cer[AP], very long-chain CER[EOH], and CER[EOS], were significantly decreased in S. aureus colonization compared to non-colonization. This suggests that alterations in the length of ceramide acyl chains in epidermal lipids can influence S. aureus colonization. Wang et al. analyzed the facial sebum composition of 28 AD infants and healthy infants using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and identified 29 significantly different lipid markers. They provided a clear analysis of the facial sebum distribution characteristics in AD infants, indicating a close correlation between skin barrier dysfunction in AD lesions and lipid types, levels, and structures. Robust lipidomic techniques have fully revealed the lipid profiles of AD. Although the relationship between these lipid changes and AD pathogenesis remains unclear, this will facilitate further exploration of the pathogenesis and treatment strategies for AD.
Application of Lipidomics in Melasma
Melasma is an acquired pigmentary disorder previously thought to be associated with factors such as ultraviolet radiation, sex hormones, and genetics. Bioinformatics analysis studies have shown that, besides upregulation of melanin-related gene expression, most lipid metabolism-related genes are downregulated in melasma lesions, which is related to impaired barrier function. Xu et al. further investigated the epidermal lipid composition of melasma lesions and found a significant increase in ceramide levels in melasma lesions, possibly as a compensatory mechanism to maintain skin barrier function. Additionally, some key lipid substances are expressed at lower levels in highly activated melanocytic lesions, indicating that patients with melasma require better skin barrier protection.
Application of Lipidomics in Senile Pruritus
Senile pruritus is a common skin condition in the elderly population, and its pathogenesis remains unclear. Some studies suggest that age-related skin barrier damage and changes in epidermal lipid composition play important roles in the pathogenesis of senile pruritus. Ma et al. used LC-MS to analyze changes in skin surface lipid composition in patients with senile pruritus and found significant separation of skin surface lipid profiles between patients with senile pruritus and healthy controls based on partial least squares discriminant analysis. Several major lipids, such as glycerides, fatty acids, phosphatidylcholine, phosphatidylethanolamine, and sphingosine, were significantly increased in senile pruritus patients, while triglycerides were significantly decreased. The study also found that some types of ceramides were positively correlated with transepidermal water loss, and certain subtypes of sphingomyelin and ceramides were correlated with the degree of itching. This suggests that changes in certain skin surface lipid components in senile pruritus patients are associated with skin barrier damage and further induce itching symptoms. Further research into the mechanisms of these lipid component changes in pruritus is of great value for exploring the pathogenesis of senile pruritus.
Identification of differential lipids and lipid metabolites between senile pruritus patients and healthy person controls (Ma et al., 2020).
Reference
- Ma, Xiaolei, et al. "Lipidomics profiling of skin surface lipids in senile pruritus." Lipids in health and disease 19 (2020): 1-10.
