Metabolomics Signature and Potential Application of Serum Polyunsaturated Fatty Acids Metabolism in Patients With Vitiligo

Abstract

Vitiligo is a depigmented skin disorder caused by a variety of factors, including autoimmune, metabolic disturbance or their combined effect, etc. Non-targeted metabolomic analyses have denoted that dysregulated fatty acids metabolic pathways are involved in the pathogenesis of vitiligo. However, the exact category of fatty acids that participate in vitiligo development and how they functionally affect CD8+ T cells remain undefined. We aimed to determine the difference in specific fatty acids among vitiligo patients and healthy individuals and to investigate their association with clinical features in patients with vitiligo. Serum levels of fatty acids in 48 vitiligo patients and 28 healthy individuals were quantified by performing ultra-performance liquid chromatography-tandem mass spectrometry. Univariate and multivariate analyses were carried out to evaluate the significance of differences. Moreover, flow cytometry was used to explore the effect of indicated fatty acids on the function of CD8+ T cells derived from patients with vitiligo. We demonstrated that serological level of alpha-linolenic acid (ALA) was markedly upregulated, while that of arachidonic acid (ARA), arachidic acid (AA) and behenic acid were significantly downregulated in patients with vitiligo. Moreover, ALA levels were positively associated with vitiligo area scoring index (VASI) and ARA was a probable biomarker for vitiligo. We also revealed that supplementation with ARA or nordihydroguaiaretic acid (NDGA) could suppress the function of CD8+ T cells. Our results showed that vitiligo serum has disorder-specific phenotype profiles of fatty acids described by dysregulated metabolism of polyunsaturated fatty acids. Supplementation with ARA or NDGA might promote vitiligo treatment. These findings provide novel insights into vitiligo pathogenesis that might add to therapeutic options.

Influences of vitiligo‐associated characteristics on the occurrence of diabetes mellitus: Interactive analysis of a cross‐sectional study

“…A case control study from Turkey discovered that an increased percentage in the affected BSA were determined to be independent predictors of metabolic syndrome 26 . Our recent study has indicated that the severity of vitiligo is significantly associated with abnormal accumulation of metabolite 27 . Thus, we speculate that metabolic imbalance may be a potential cause for DM occurrences in patients with vitiligo, which needs further study.…”

“…26 Our recent study has indicated that the severity of vitiligo is significantly associated with abnormal accumulation of metabolite. 27 Thus, we speculate that metabolic imbalance may be a potential cause for DM occurrences in patients with vitiligo, which needs further study.…”

Validation of the DLQI questionnaire in assessing the disease burden and principal aspects related to life quality of vitiligo patients

“…Vitiligo is the most commonly acquired complex disorder of pigmentation, with a prevalence of ~1% in the world population (Ezzedine et al, 2015 ; Ye et al, 2022 ; Yu et al, 2022 ). It is characterized by well-circumscribed depigmented macules and patches that result from a progressive loss of functional melanocytes.…”

Mechanisms of Arachidonic Acid In Vitro Tumoricidal Impact

“…Oral supplementation with ARA is not expected to lead to serum and tissues ARA concentrations higher than 50 μM for a brief period because albumin specifically binds to fatty acids. This rapidly reduces the concentration of free fatty acids to below 0.1 μM while permitting far higher concentrations, from 20 μM to >3 mM, to be stabilized in blood and tissues [ 29 , 30 , 31 , 32 , 33 ]. Of note, in vitro exposure to 50 μM ARA does not impair T cell viability [ 33 ].…”

“…This rapidly reduces the concentration of free fatty acids to below 0.1 μM while permitting far higher concentrations, from 20 μM to >3 mM, to be stabilized in blood and tissues [ 29 , 30 , 31 , 32 , 33 ]. Of note, in vitro exposure to 50 μM ARA does not impair T cell viability [ 33 ]. Accordingly, we opted for 30 min exposure of tumor and normal cell lines to fetal calf serum-free medium supplemented with 50 μM ARA to investigate the ARA tumoricidal mechanism(s).…”