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A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Cell Metabolism".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 26903

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Special Issue Editor

Prof. Dr. Zhuzhen Zhang

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Guest Editor

College of Life Sciences, Wuhan University, Wuhan 430072, China
Interests: skin; metabolism; lipids; dermal adipose tissue; metabolic syndrome

Special Issue Information

Dear Colleagues,

Skin is the largest organ in the human body and serves as the outermost layer in direct contact with the environment. Over the past few years, many studies have demonstrated the importance of active metabolic processes in the skin with associations between the dysregulation of metablic pathways and skin disorders, such as psoriasis, acne, androgenetic alopecia, atopic dermatitis, diabetic foot skin, and skin tumors.

Though metabolic processes play essential roles in the development and physiological/pathological function of skin, the underlying mechanisms are complex and are not yet well understood.

This Special Issue of metabolites aims to explore cutting-edge research related to metabolism and skin disorders. We welcome articles pertaining to the following topics: metablolic syndrome and skin disorders, metabolic pathways and skin functions, and metabolism in skin tumors and related topics and specific skin dissorders. We believe that this will bring together current knowledge about metabolism in relation to skin disorders, and help pave the way for the development of new therapies aimed at restoring healthy skin.

Prof. Dr. Zhuzhen Zhang
Guest Editor

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Keywords

metabolism
skin disorders
metabolic syndrome
skin tumors

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Published Papers (10 papers)

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Research

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11 pages, 1167 KiB

Open AccessArticle

Lipid Metabolism Traits Mediate the Effect of Psoriasis on Myocardial Infarction Risk: A Two-Step Mendelian Randomization Study

by Yang Ding, Shengyi Yang, Mengjiao He, Shasha Fan, Xiaohua Tao and Wei Lu

Metabolites 2023, 13(9), 976; https://doi.org/10.3390/metabo13090976 - 28 Aug 2023

Cited by 2 | Viewed by 2009

Abstract

Mendelian randomization (MR) analysis was performed to explore the effect of psoriasis on lipid metabolism traits and myocardial infarction (MI) risk and to analyze the proportion of the mediatory effect of lipid metabolism traits. Publicly accessible summary-level data for psoriasis, lipid metabolism traits, and MI were provided by the genome-wide association studies (GWASs) of the FinnGen Biobank, UK Biobank, and CARDIoGRAMplusC4D, respectively. A two-sample MR was carried out to evaluate the association of psoriasis with lipid metabolism traits and MI. Furthermore, the current research focused on determining if the impact of psoriasis on MI is mediated by lipid metabolism traits. The outcomes of the random effect inverse-variance-weighted (IVW) technique indicated a substantial link between genetically predicted psoriasis and a higher risk of low-density lipoprotein (LDL) cholesterol (OR: 1.006, 95% CI: 1.005–1.007, p = 0.024), apolipoprotein B (OR: 1.018, 95% CI: 1.010–1.026, p = 0.015), lipoprotein A (OR: 1.006, 95% CI: 1.002–1.010, p = 0.039), and MI (OR: 1.066, 95% CI: 1.014–1.121, p = 0.012). The percentages of the mediatory effect of LDL cholesterol, apolipoprotein B, and lipoprotein A under psoriasis conditions on MI risk was 7.4%, 10.2%, and 4.1%, respectively. Psoriasis was causally linked to an elevated risk of lipid metabolism levels and MI. This study further demonstrated that LDL cholesterol, apolipoprotein B, and lipoprotein A mediated the effect of psoriasis on MI risk. And timely lipid-lowering treatment should be given to MI patients. Full article

(This article belongs to the Special Issue Skin Metabolism and Cutaneous Disorders)

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12 pages, 4212 KiB

Open AccessArticle

Human Skin Drug Metabolism: Relationships between Methyl Salicylate Metabolism and Esterase Activities in IVPT Skin Membranes

by Krishna C. Telaprolu, Jeffrey E. Grice, Yousuf H. Mohammed and Michael S. Roberts

Metabolites 2023, 13(8), 934; https://doi.org/10.3390/metabo13080934 - 9 Aug 2023

Cited by 6 | Viewed by 2391

Abstract

The presence of esterase enzymes in human skin and their role in drug metabolism has been reported, but their distribution in the various skin layers and the relative contributions of those layers to metabolism is poorly defined. To gain further insight into esterase distribution, we performed in vitro skin permeation of a commercial 28.3% methyl salicylate (MeSA) cream (Metsal™) in Franz diffusion cells, using a range of human skin membranes, all from the same donor. The membranes were viable epidermis separated by a dispase II enzymatic method, heat separated epidermis, dermatomed skin, and dermis separated by a dispase II enzymatic method. Methyl salicylate and its metabolite, salicylic acid (SA), were measured by high-performance liquid chromatography. Alpha naphthyl acetate and Hematoxylin and Eosin staining provided qualitative estimations of esterase distribution in these membranes. The permeation of methyl salicylate after 24 h was similar across all membranes. Salicylic acid formation and permeation were found to be similar in dermatomed skin and dermis, suggesting dermal esterase activity. These results were supported by the staining studies, which showed strong esterase activity in the dermal–epidermal junction region of the dermis. In contrast with high staining of esterase activity in the stratum corneum and viable epidermis, minimal stained and functional esterase activity was found in heat-separated and dispase II-prepared epidermal membranes. The results are consistent with dispase II digesting hemidesmosomes, penetrating the epidermis, and affecting epidermal esterases but not those in the dermis. Accordingly, whilst the resulting dispase II-generated dermal membranes may be used for in vitro permeation tests (IVPT) involving esterase-based metabolic studies, the dispase II-generated epidermal membranes are not suitable for this purpose. Full article

(This article belongs to the Special Issue Skin Metabolism and Cutaneous Disorders)

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14 pages, 1971 KiB

Open AccessArticle

Lipid Differences and Related Metabolism Present on the Hand Skin Surface of Different-Aged Asiatic Females—An Untargeted Metabolomics Study

by Tian Chen, Juan Wang and Zhenxing Mao

Metabolites 2023, 13(4), 553; https://doi.org/10.3390/metabo13040553 - 13 Apr 2023

Cited by 1 | Viewed by 1771

Abstract

This cross-sectional study aimed to investigate differences in skin surface lipids (SSL) and explore related metabolic pathways among females of different ages in Henan Province. Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used to determine the lipid composition of the skin surface of 58 female volunteers who were divided into three age groups. Statistical analysis was performed using Progenesis QI, Ezinfo, and MetaboAnalyst. Multivariate and enrichment analysis were used to identify the different SSL among the groups. A total of 530 lipid entities were identified and classified into eight classes. Among these, 63 lipids were significantly different between the groups. Lower levels of glycerolipids (GLs) and sphingolipids (SPs) were observed in the middle-aged group, while higher levels of GLs were found in the elder group. GLs belonged to the largest and statistically significant enrichment of lipid metabolic pathways, and the lipid individuals enriched to the sphingoid bases metabolism were the most and statistically significant. These findings suggest that there are differences in hand SSL among females of different ages, which may be related to GLs and sphingoid bases metabolism. Full article

(This article belongs to the Special Issue Skin Metabolism and Cutaneous Disorders)

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12 pages, 2183 KiB

Open AccessArticle

Positive Correlation of Triacylglycerols with Increased Chain Length and Unsaturation with ω-O-Acylceramide and Ceramide-NP as Well as Acidic pH in the Skin Surface of Healthy Korean Adults

by Ju-Young Lee, Sanghun Jeon, Sangshin Han, Kwang-Hyeon Liu, Yunhi Cho and Kun-Pyo Kim

Metabolites 2023, 13(1), 31; https://doi.org/10.3390/metabo13010031 - 24 Dec 2022

Cited by 6 | Viewed by 2980

Abstract

Triacylglycerols (TG) play an important role in skin homeostasis including the synthesis of ω-O-acylceramides (acylCER) required for skin barrier formation by providing linoleic acid (C18:2n6). However, the overall relationships of TG species with various ceramides (CER) including CER-NP, the most abundant CER, ω-O-acylCER, and another acylCER, 1-O-acylCER in human SC, remain unclear. Therefore, we investigated these relationships and their influence on skin health status in healthy Korean adults. Twelve CER subclasses including two ω-O-acylCER and two 1-O-acylCER were identified with CER-NP consisting of approximately half of the total CER. The ω-O-acylCER species exhibited positive relationships with TG 52:4 and TG 54:2 containing C18:2, while interestingly, 1-O-acylCER containing ester-linked C14:0 and C16:0 demonstrated positive relationships with TG 46–50 including C14:0 and C16:0, respectively. In addition, CER-NP and CER-NH showed positive correlations with TG 52–54 containing C18:2 or C18:3. A lipid pattern with higher levels of CER including CER-NP and ω-O-acylCER with TG 54 and TG with 5–6 double bonds was related to good skin health status, especially with acidic skin pH. Collectively, TG with increased chain length and unsaturation seemed to improve CER content, and profiles such as higher acylCER and CER-NP improved skin health status by fortifying skin barrier structure. Full article

(This article belongs to the Special Issue Skin Metabolism and Cutaneous Disorders)

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9 pages, 404 KiB

Open AccessArticle

The Association between Blood Lipids and Systemic Lupus Erythematosus: A Two-Sample Mendelian Randomization Research

by Yang Ding, Shasha Fan, Yi Tang, Mengjiao He, Mingyang Ren, Yunjuan Shi, Xiaohua Tao and Wei Lu

Metabolites 2023, 13(1), 27; https://doi.org/10.3390/metabo13010027 - 23 Dec 2022

Cited by 3 | Viewed by 2550

Abstract

We evaluated the causal effects of blood lipid levels on systemic lupus erythematosus with a two-sample Mendelian randomization analysis. Independent single-nucleotide polymorphisms related to blood lipids levels (p < 5 × 10⁻⁸) were selected as instrumental variables (IVs) from a published genome-wide association study (GWAS). SLE GWAS analysis that included 4036 cases and 6959 controls of European ancestry provided the related roles between instrumental variables and result (SLE). The causal effects were evaluated with two-sample Mendelian randomization (MR) analyses. According to the inverse-variance weighted approaches, genes predictive of increased LDL cholesterol (OR: 1.131; 95% CI: 0.838, 1.528; p = 0.420), HDL cholesterol (OR: 1.093; 95% CI: 0.884, 1.352; p = 0.412), triglycerides (OR: 0.903; 95% CI: 0.716, 1.137; p = 0.384), Apolipoprotein A-I (OR: 0.854; 95% CI: 0.680, 1.074; p = 0.177), and Apolipoprotein B (OR: 0.933; 95% CI: 0.719, 1.211; p = 0.605) were not causally related to the risk of SLE, consistent with multivariate Mendelian randomization analysis. The reverse-MR analyses showed no massive causal roles between SLE and LDL cholesterol (OR: 0.998; 95% CI: 0.994, 1.001; p = 0.166) as well as Apolipoprotein B (OR: 0.998; 95% CI: 0.994, 1.001; p = 0.229). Nevertheless, a causal role of SLE in decreasing HDL cholesterol (OR: 0.993; 95% CI: 0.988, 0.997; p = 0.002), triglycerides (OR: 0.996; 95% CI: 0.993, 0.999; p = 0.010), and Apolipoprotein A-I (OR: 0.995; 95% CI: 0.990, 0.999; p = 0.026) was validated to some extent. Our study found no causal association between abnormal blood lipids and SLE nor a causal effect between SLE and LDL cholesterol as well as Apolipoprotein B. Nevertheless, some evidence showed that SLE exerted a causal effect on lowering HDL cholesterol, Apolipoprotein A-I, and triglyceride levels. Full article

(This article belongs to the Special Issue Skin Metabolism and Cutaneous Disorders)

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Review

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16 pages, 1559 KiB

Open AccessReview

Iron Metabolism of the Skin: Recycling versus Release

by Marta Surbek, Supawadee Sukseree and Leopold Eckhart

Metabolites 2023, 13(9), 1005; https://doi.org/10.3390/metabo13091005 - 12 Sep 2023

Cited by 4 | Viewed by 3235

Abstract

The skin protects the body against exogenous stressors. Its function is partially achieved by the permanent regeneration of the epidermis, which requires high metabolic activity and the shedding of superficial cells, leading to the loss of metabolites. Iron is involved in a plethora of important epidermal processes, including cellular respiration and detoxification of xenobiotics. Likewise, microorganisms on the surface of the skin depend on iron, which is supplied by the turnover of epithelial cells. Here, we review the metabolism of iron in the skin with a particular focus on the fate of iron in epidermal keratinocytes. The iron metabolism of the epidermis is controlled by genes that are differentially expressed in the inner and outer layers of the epidermis, establishing a system that supports the recycling of iron and counteracts the release of iron from the skin surface. Heme oxygenase-1 (HMOX1), ferroportin (SLC40A1) and hephaestin-like 1 (HEPHL1) are constitutively expressed in terminally differentiated keratinocytes and allow the recycling of iron from heme prior to the cornification of keratinocytes. We discuss the evidence for changes in the epidermal iron metabolism in diseases and explore promising topics of future studies of iron-dependent processes in the skin. Full article

(This article belongs to the Special Issue Skin Metabolism and Cutaneous Disorders)

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15 pages, 1276 KiB

Open AccessReview

Bacterial Metabolites and Inflammatory Skin Diseases

by Victoria Jiminez and Nabiha Yusuf

Metabolites 2023, 13(8), 952; https://doi.org/10.3390/metabo13080952 - 17 Aug 2023

Cited by 3 | Viewed by 2681

Abstract

The microbiome and gut-skin axis are popular areas of interest in recent years concerning inflammatory skin diseases. While many bacterial species have been associated with commensalism of both the skin and gastrointestinal tract in certain disease states, less is known about specific bacterial metabolites that regulate host pathways and contribute to inflammation. Some of these metabolites include short chain fatty acids, amine, and tryptophan derivatives, and more that when dysregulated, have deleterious effects on cutaneous disease burden. This review aims to summarize the knowledge of wealth surrounding bacterial metabolites of the skin and gut and their role in immune homeostasis in inflammatory skin diseases such as atopic dermatitis, psoriasis, and hidradenitis suppurativa. Full article

(This article belongs to the Special Issue Skin Metabolism and Cutaneous Disorders)

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16 pages, 1679 KiB

Open AccessReview

Abnormalities of Sphingolipids Metabolic Pathways in the Pathogenesis of Psoriasis

by Beatriz Burger, Roberta Nicolli Sagiorato, Isabella Cavenaghi and Hosana Gomes Rodrigues

Metabolites 2023, 13(2), 291; https://doi.org/10.3390/metabo13020291 - 16 Feb 2023

Cited by 10 | Viewed by 3259

Abstract

Psoriasis is immune-mediated skin disorder affecting thousands of people. Sphingolipids (SLs) are bioactive molecules present in the epidermis, involved in the following cellular processes: proliferation, differentiation, and apoptosis of keratinocytes. Alterations in SLs synthesis have been observed in psoriatic skin. To investigate if the imbalance in lipid skin metabolism could be related to psoriasis, we analyzed the gene expression in non-lesioned and lesioned skin of patients with psoriasis available in two datasets (GSE161683 and GSE136757) obtained from National Center for Biotechnology Information (NCBI). The differentially expressed genes (DEGs) were searched for using NCBI analysis, and Gene Ontology (GO) biological process analyses were performed using the Database of Annotation, Visualization, and Integrated Discovery (DAVID) platform. Venn diagrams were done with InteractiVenn tool and heatmaps were constructed using Morpheus software. We observed that the gene expression of cytoplasmic phospholipase A₂ (PLA2G4D), glycerophosphodiester phosphodiesterase domain containing 3 (GDP3), arachidonate 12-lipoxygenase R type (ALOX12B), phospholipase B-like 1 (PLBD1), sphingomyelin phosphodiesterase 3 (SMPD3), ganglioside GM2 activator (GM2A), and serine palmitoyltransferase long chain subunit 2 (SPTLC2) was up-regulated in lesioned skin psoriasis when compared with the non-lesioned skin. These genes are related to lipid metabolism and more specifically to sphingolipids. So, in the present study, the role of sphingolipids in psoriasis pathogenesis is summarized. These genes could be used as prognostic biomarkers of psoriasis and could be targets for the treatment of patients who suffer from the disease. Full article

(This article belongs to the Special Issue Skin Metabolism and Cutaneous Disorders)

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10 pages, 864 KiB

Open AccessReview

PNPLA1-Mediated Acylceramide Biosynthesis and Autosomal Recessive Congenital Ichthyosis

by Fansi Zeng, Wenzhen Qin, Feifei Huang and Pingan Chang

Metabolites 2022, 12(8), 685; https://doi.org/10.3390/metabo12080685 - 26 Jul 2022

Cited by 1 | Viewed by 2065

Abstract

The stratum corneum of the epidermis acts as a life-sustaining permeability barrier. Unique heterogeneous ceramides, especially ω-O-acylceramides, are key components for the formation of stable lamellar membrane structures in the stratum corneum and are essential for a vital epidermal permeability barrier. Several enzymes involved in acylceramide synthesis have been demonstrated to be associated with ichthyosis. The function of patatin-like phospholipase domain-containing protein 1 (PNPLA1) was a mystery until the finding that PNPLA1 gene mutations were involved in autosomal-recessive congenital ichthyosis (ARCI) patients, both humans and dogs. PNPLA1 plays an essential role in the biosynthesis of acylceramide as a CoA-independent transacylase. PNPLA1 gene mutations cause decreased acylceramide levels and impaired skin barrier function. More and more mutations in PNPLA1 genes have been identified in recent years. Herein, we describe the structural and functional specificity of PNPLA1, highlight its critical roles in acylceramide synthesis and skin barrier maintenance, and summarize the PNPLA1 mutations currently identified in ARCI patients. Full article

(This article belongs to the Special Issue Skin Metabolism and Cutaneous Disorders)

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16 pages, 822 KiB

Open AccessSystematic Review

The Bowel-Associated Arthritis–Dermatosis Syndrome (BADAS): A Systematic Review

by Italo Francesco Aromolo, Domenico Simeoli, Carlo Alberto Maronese, Andrea Altomare, Daniele Noviello, Flavio Caprioli and Angelo Valerio Marzano

Metabolites 2023, 13(7), 790; https://doi.org/10.3390/metabo13070790 - 25 Jun 2023

Cited by 3 | Viewed by 2378

Abstract

Bowel-associated arthritis–dermatosis syndrome (BADAS) is a rare neutrophilic dermatosis that was first described in 1971 in patients who underwent bypass surgery for obesity. Over the years, the number of reported cases associated with medical gastroenterological conditions, particularly inflammatory bowel disease (IBD), has progressively increased. To date, there are no systematic reviews in the literature on BADAS. The design of an a priori protocol was based on PRISMA guidelines, and a search of PubMed and Scopus databases was conducted for articles published between 1971 and 2023 related to the topic. Fifty-one articles including 113 patients with BADAS were analyzed in this systematic review. Bariatric surgery and IBD were the most frequently reported causes of BADAS, accounting for 63.7% and 24.7% of all cases, respectively. A total of 85% of cases displayed the typical dermatological presentation, including urticarial maculopapular lesions centered by a vesicopustule, with the majority of lesions located on the upper limbs (73.5%). Polyarthralgia or localized arthritis were always present. Atypical presentations included cellulitis-like, erythema-nodosum-like, Sweet-syndrome-like and pyoderma-gangrenosum-like manifestations. Gastrointestinal symptoms were frequently observed in IBD-related cases (67.9%). The histopathology showed a neutrophilic infiltrate (96.6%). The most commonly used treatment regimens consisted of systemic corticosteroids, metronidazole and tetracyclines, either alone or in combination. A relapsing–remitting course was observed in 52.1% of patients. In conclusion, BADAS is a neutrophilic dermatosis that presents with a wide variety of cutaneous manifestations, both typical and atypical. Gastrointestinal symptoms are frequently observed, particularly in cases related to IBD. The histopathology is clear but not specific compared with other neutrophilic dermatoses. The diagnosis can be challenging, but the relapsing–remitting course and the strong association with polyarthralgia and gastrointestinal disease can aid in the diagnosis. Full article

(This article belongs to the Special Issue Skin Metabolism and Cutaneous Disorders)

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