Noninvasive profiling of sweat‐derived lipid mediators for cutaneous research

Agrawal, Karan; Sivamani, Raja K; Newman, John W.

doi:10.1111/srt.12617

“…Studies on the composition of free SBs in AD are scarce. Agrawal et al [26] found increased levels of sphingosine in the sweat of AD patients, however contrary to these results Arikawa et al [27] reported decreased sphingosine levels in the lesional and non-lesional skin of AD patients.…”

Section: Discussionmentioning

confidence: 87%

Altered Levels of Sphingosine, Sphinganine and Their Ceramides in Atopic Dermatitis Are Related to Skin Barrier Function, Disease Severity and Local Cytokine Milieu

Tončić

¹

,

Jakaša

²

,

Hadžavdić

³

et al. 2020

IJMS

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Dysfunctional skin barrier plays a key role in the pathophysiology of atopic dermatitis (AD), a common inflammatory skin disease. Altered composition of ceramides is regarded as a major cause of skin barrier dysfunction, however it is not clear whether these changes are intrinsic or initiated by inflammation and aberrant immune response in AD. This study investigated the levels of free sphingoid bases (SBs) sphingosine and sphinganine and their ceramides and glucosylceramide in the stratum corneum (SC) and related them to skin barrier function, disease severity and local cytokine milieu. Ceramides were measured in healthy skin, and lesional and non-lesional skin of AD patients by a novel method based on deacylation of ceramides which were subsequently determined as corresponding sphingoid bases by using liquid chromatography–tandem mass spectrometry (LC–MS/MS). The cytokine levels were determined by multiplex immunoassay. Atopic skin showed increased levels of most investigated markers, predominantly in lesional skin. The largest difference in respect to healthy skin was found for glucosylceramide with respective median values of 0.23 (IQR 0.18–0.61), 0.56 (IQR 0.32–0.76) and 19.32 (IQR 7.86–27.62) pmol/g protein for healthy, non-lesional and lesional skin. The levels of investigated ceramide markers were correlated with disease severity (scoring atopic dermatitis, SCORAD) and skin barrier function (trans-epidermal water loss, TEWL) and furthermore with cytokines involved in innate, Th-1, and Th-2 immune response. Interestingly, the strongest association with SCORAD was found for sphinganine/sphingosine ratio (r = −0.69, p < 0.001; non-lesional skin), emphasizing the importance of SBs in AD. The highest correlation with TEWL was found for glucosylceramide (r2 = 0.60, p < 0.001), which was investigated for the first time in AD. Findings that the changes in SBs and ceramide levels were predominant in lesional skin and their association with disease severity and cytokine levels suggest an immune-system driven effect. a novel analysis method demonstrates a robust and simple approach that might facilitate wider use of lipid biomarkers in the clinics e.g., to monitor (immune) therapy or dissect disease endotypes.

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“…Julia Oh 85 compared metabolites derived from differing skin sites and emphasized the marked variation between individuals. Others explored the potential importance of measuring sweat metabolites in studies of the skin 86 . None of these studies focused specifically on obesity or the ethnicity of the subjects.…”

Section: Discussionmentioning

confidence: 99%

Obesity and ethnicity alter gene expression in skin

Walker

¹

,

Garcet

²

,

Alemán

³

et al. 2020

Sci Rep

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Obesity is accompanied by dysfunction of many organs, but effects on the skin have received little attention. We studied differences in epithelial thickness by histology and gene expression by Affymetrix gene arrays and PCR in the skin of 10 obese (BMI 35-50) and 10 normal weight (BMI 18.5-26.9) postmenopausal women paired by age and ethnicity. Epidermal thickness did not differ with obesity but the expression of genes encoding proteins associated with skin blood supply and wound healing were altered. In the obese, many gene expression pathways were broadly downregulated and subdermal fat showed pronounced inflammation. There were no changes in skin microbiota or metabolites. African American subjects differed from European Americans with a trend to increased epidermal thickening. In obese African Americans, compared to obese European Americans, we observed altered gene expression that may explain known differences in water content and stress response. African Americans showed markedly lower expression of the gene encoding the cystic fibrosis transmembrane regulator characteristic of the disease cystic fibrosis. The results from this preliminary study may explain the functional changes found in the skin of obese subjects and African Americans. Obesity, defined as a body mass index (BMI) greater than 30 kg/m 21 , has become a major epidemic in industrial and emerging countries. The prevalence of obesity has doubled since the 1980s and it is now estimated that 600 million adults worldwide are obese 2. Obesity affects many organs of the body and it is this organ dysfunction that leads to excess mortality and morbidity 3. Much attention has focused on the consequences of obesity in the heart, liver and pancreas and other organs in which increased inflammation and oncogenesis become apparent 4. Less attention has been paid to the effects of obesity on the skin. Obesity increases psoriasis 5 , which can be ameliorated with weight loss, and cutaneous infections 6. Since diabetes is common in obesity, disorders such as fibroepithelial polyps and acanthosis nigricans also occur in the skin of obese subjects 7,8. Moreover, physiologic changes found in obese skin include increased trans-epidermal water loss with lower capacitance, dry, rough textured skin with pronounced erythema and reduced microvascular reactivity. Altered collagen formation and increased delayed-type hypersensitivity have also been reported 9. Adipocyte depots that exist adjacent to the epidermis have distinct morphology and physiologic characteristics and are termed dermal or subdermal adipose tissue. In addition to the principal role for dermal adipocytes in lipid storage and thermal insulation 10 , they also promote skin immunity 11 , wound healing, and hair follicle cycling 12. Obesity is accompanied by inflammatory immune changes in subcutaneous and visceral adipose tissues 13 , but the role of inflammatory changes within the adipose layer of the skin has received little attention. Furthermore, obesity is associated with increased circulating leptin...

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“…Others explored the potential importance of measuring sweat metabolites in studies of the skin [80]. None of these studies focused specifically on obesity or the ethnicity of the subjects.…”

Section: The Most Detailed Previous Evaluation Of Differences Betweenmentioning

confidence: 99%

Obesity and Race Alter Gene Expression in Skin

Walker

¹

,

Garcet

²

,

Alemán

³

et al. 2020

Preprint

0

View full text Add to dashboard Cite

Obesity is accompanied by dysfunction of many organs, but effects on the skin have received little attention. We studied differences in epithelial thickness by histology and gene expression by Affymetrix gene arrays and PCR in the skin of 10 obese (BMI 35-50) and 10 normal weight (BMI 18.5-26.9) postmenopausal women paired by age and race. Epidermal thickness did not differ with obesity but the expression of genes encoding proteins associated with skin blood supply and wound healing were altered. In the obese, many gene expression pathways were broadly downregulated and subdermal fat showed pronounced inflammation. There were no changes in skin microbiota or metabolites. African American subjects differed from Caucasians with a trend to increased epidermal thickening. In obese African Americans, compared to obese Caucasians, we observed altered gene expression that may explain known differences in water content and stress response. African Americans showed markedly lower expression of the gene encoding the cystic fibrosis transmembrane regulator characteristic of the disease cystic fibrosis. The results from this preliminary study may explain the functional changes found in the skin of obese subjects and African Americans.

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Noninvasive profiling of sweat‐derived lipid mediators for cutaneous research

Cited by 13 publications

References 85 publications

Altered Levels of Sphingosine, Sphinganine and Their Ceramides in Atopic Dermatitis Are Related to Skin Barrier Function, Disease Severity and Local Cytokine Milieu

Altered Levels of Sphingosine, Sphinganine and Their Ceramides in Atopic Dermatitis Are Related to Skin Barrier Function, Disease Severity and Local Cytokine Milieu

Obesity and ethnicity alter gene expression in skin

Obesity and Race Alter Gene Expression in Skin

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