Metabolomic profiling reveals amino acid and carnitine alterations as metabolic signatures in psoriasis

Abstract

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.

Metabolomics Studies in Psoriatic Disease: A Review

“…While a few studies have examined the metabolite profiles of patients with autoimmune diseases (ADs) [9,10], or immunemediated inflammatory diseases (IMIDs) with no emphasis on Ps or PsA specifically [11], the majority of studies included in this review sought to identify metabolites that were associated with Ps by investigating Ps patients in comparison to healthy volunteers [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. Other studies focused on identifying metabolite profiles in Ps patients and correlating them with different measurements of disease activity [13,19,22,28,32,33]. Another important question in psoriatic disease that has garnered much interest pertains to determining which Ps patients have or will develop PsA.…”

“…Most studies included in our literature search were non-hypothesis driven and therefore employed an untargeted metabolomics approach [12,[14][15][16][19][20][21][22][23]25,26,[31][32][33]36,41,42]. However, there were several studies that analyzed specific metabolites using a targeted metabolomics approach [9,10,13,18,24,27,28,30,39,40].…”

“…Contrastingly, plasma does not undergo the coagulation process and thus takes less time to process and contains additional clotting proteins not present in serum [45]. There were fewer studies that investigated metabolites in plasma [18][19][20][21]32,36,42]. Many of the studies that examined metabolites in the blood of patients with psoriatic disease required subjects to fast prior to sample collection.…”

“…Protein precipitation (PPt) is another widely used sample preparation method for biological fluids that can sometimes be categorized as an LLE method since it requires usually the addition of cold solvent to allow the precipitation of proteins from the sample, which are then effectively removed, leaving only the metabolites [44]. PPt shares many of the same benefits and limitations as LLE [44], and the majority of studies included in this review used PPt to isolate metabolites and prepare the sample before analysis [13,[15][16][17][19][20][21]29,30,32,33,36,39,40,42].…”

“…Tandem mass spectrometry (MS/MS) acquires additional information about specific metabolites by selecting them for an additional fragmentation step. The majority of studies included in this review used LC-MS based platforms [13,16,17,[19][20][21][23][24][25]27,28,30,32,33,39,40], while much fewer number of studies employed GC-MS to analyze metabolites [9,10,12,15]. Other studies employed both LC-MS and GC-MS as their analytical techniques [18,29,34].…”