Metabolomic profiling reveals amino acid and carnitine alterations as metabolic signatures in psoriasis.
Metabolomic profiling reveals amino acid and carnitine alterations as metabolic signatures in psoriasis.
复制标题
代谢组学分析揭示了氨基酸和肉碱的改变是牛皮癣的代谢特征。
作者：
Chen C;Hou G;Zeng C;Ren Y;Chen X;Peng C
高通量代谢物分析提供了揭示代谢机制和识别生物标志物的机会。牛皮癣是一种免疫介导的慢性炎症性疾病。然而，代谢在银屑病发病机制中的作用仍不清楚。方法：收集个体（45 名银屑病患者和 45 名性别、年龄和 BMI 匹配的健康对照）的血浆样本。进行非靶向代谢组学和氨基酸或肉碱靶向代谢组学，然后对咪喹莫特（IMQ）诱导的小鼠血浆样本进行氨基酸和肉碱靶向代谢组学分析。采用流式细胞术研究左旋肉碱 (LC(C0)) 对 IMQ 诱导的银屑病炎症的影响。结果：通过非靶向代谢组学方法，我们检测到银屑病患者的氨基酸和肉碱显着改变。氨基酸靶向代谢组学分析确定了银屑病中发生改变的 37 个氨基酸，其中 23 个氨基酸显着上调，包括必需氨基酸 (EAA) 和支链氨基酸 (BCAA)，而谷氨酰胺、半胱氨酸和天冬酰胺显着下调。肉碱靶向代谢组学分析确定了 40 种显着改变的肉碱，其中 14 种包括棕榈酰肉碱 (C16)，在银屑病中显着下调，而己酰肉碱 (C6) 和 3-OH-十八碳烯酰肉碱 (C18:1-OH) 显着上调。有趣的是，谷氨酰胺、天冬酰胺和 C16 水平与 PASI 评分呈负相关。此外，较高丰度的 LC(C0) 与 IMQ 诱导的表皮增厚和皮损中 Th17 细胞浸润的显着减少相关，表明补充 LC(C0) 是治疗银屑病的潜在疗法。结论：我们的研究结果表明，银屑病中氨基酸和肉碱的代谢显着改变，尤其是 EAA、BCAA 和 LC(C0) 的代谢，可能在银屑病的发病机制中起关键作用。
High-throughput metabolite profiling provides the opportunity to reveal metabolic mechanisms and identify biomarkers. Psoriasis is an immune-mediated chronic inflammatory disease. However, the role of metabolism in psoriasis pathogenesis remains unclear. Methods: Plasma samples of individuals (45 psoriasis and 45 sex‐, age-, and BMI-matched healthy controls) were collected. Non-targeted metabolomics and amino acid- or carnitine-targeted metabolomics were conducted, then, plasma samples of mice induced by imiquimod (IMQ) were subjected to the amino acid- and carnitine-targeted metabolomic profiling. Flow cytometry was used to study the effect of L-carnitine (LC(C0)) on IMQ-induced psoriatic inflammation. Results: Through the non-targeted metabolomics approach, we detected significantly altered amino acids and carnitines in psoriasis patients. Amino acid-targeted metabolomic profiling identified 37 amino acids altered in psoriasis, of these 23 were markedly upregulated, including essential amino acids (EAAs), and branched-chain amino acids (BCAAs), whereas glutamine, cysteine, and asparagine were significantly down-regulated. Carnitine-targeted metabolomic profiling identified 40 significantly altered carnitines, 14 of which included palmitoylcarnitine (C16) and were markedly downregulated in psoriasis, whereas hexanoylcarnitine (C6) and 3-OH-octadecenoylcarnitine (C18:1-OH) were significantly upregulated. Interestingly, glutamine, asparagine, and C16 levels were negatively correlated with the PASI score. Moreover, a higher abundance of LC(C0) was associated with markedly reduced IMQ-induced epidermal thickening and infiltration of Th17 cells in skin lesions, indicating LC(C0) supplementation as a potential therapy for psoriasis treatment. Conclusion: Our results suggested the metabolism of amino acids and carnitines are significantly altered in psoriasis, especially the metabolism of EAAs, BCAAs, and LC(C0), which may play key roles in the pathogenesis of psoriasis.
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影响因子：
7.4
作者：
Barrea L;Balato N;Di Somma C;Macchia PE;Napolitano M;Savanelli MC;Esposito K;Colao A;Savastano S
通讯作者：
Savastano S
影响因子：
37.8
作者：
Cheng S;Rhee EP;Larson MG;Lewis GD;McCabe EL;Shen D;Palma MJ;Roberts LD;Dejam A;Souza AL;Deik AA;Magnusson M;Fox CS;O'Donnell CJ;Vasan RS;Melander O;Clish CB;Gerszten RE;Wang TJ
通讯作者：
Wang TJ
影响因子：
7.4
作者：
Barrea L;Macchia PE;Tarantino G;Di Somma C;Pane E;Balato N;Napolitano M;Colao A;Savastano S
通讯作者：
Savastano S
影响因子：
--
作者：
Armstrong AW;Wu J;Johnson MA;Grapov D;Azizi B;Dhillon J;Fiehn O
通讯作者：
Fiehn O
影响因子：
4.5
作者：
Flanagan JL;Simmons PA;Vehige J;Willcox MD;Garrett Q
通讯作者：
Garrett Q