Metabolism and Metabolomics in Psoriasis: Research Progress and Perspectives
Psoriasis is a chronic, inflammatory, systemic, and autoimmune skin disease. It is now recognized as a systemic disease associated with metabolic abnormalities. Understanding how metabolism affects the pathophysiological processes of psoriasis holistically and systematically is crucial. Metabolomics, a new branch of systems biology, has emerged as a powerful tool in this area.
Introduction
Psoriasis was previously studied mainly from the perspective of the inflammatory immune response centered around T lymphocytes. However, recent research has shown that metabolic abnormalities play an important role in the occurrence, development, efficacy, and prognosis of psoriasis. Metabolomics, which follows genomics, proteomics, and transcriptomics, has great potential in psoriasis research and clinical applications. It can reveal the effects of exogenous factors such as diet, environment, and the microbiome, in addition to the genetic and protein aspects.
Metabolic Changes and Biomarkers in Psoriasis
Skin Lesion Samples
Metabolomics studies using skin lesion samples can provide direct and intuitive local metabolic changes. This can help integrate metabolite information with local pathological changes, inflammatory immune responses, and cell proliferation. It may play a role in discovering new topical therapeutic targets and evaluating the efficacy of existing topical drugs. For example, a study using NMR spectroscopy found a decrease in glucose levels in psoriatic lesions, which may be related to the increased energy demand due to epidermal over-proliferation.
Peripheral Blood
Psoriasis is a systemic disease, and its metabolic changes are not only local but also systemic. Metabolomics based on peripheral blood can provide an overall picture of how psoriasis affects metabolic pathways in the body. Studies have found changes in carbohydrates, lipids, amino acids, and nucleotides. For instance, in glucose metabolism, there are changes in glucose levels and related metabolites. In lipid metabolism, alterations in glycerophospholipid pathway metabolites, such as higher levels of lysophosphatidic acid (LPA), lysophosphatidylcholine (LPC), and phosphatidic acid, and lower levels of phosphatidylinositol and phosphatidylcholine, have been observed.
Urine
Urine is also a useful sample for metabolomics research. It has advantages such as convenience of access, non-invasive collection, and abundant content of in vivo metabolites. However, few studies on psoriasis have used urine as a sample source. One study analyzed urine metabolites from psoriasis patients and found lower levels of citrate, alanine, and methylsuccinate compared to healthy controls.
Role of Metabolites in the Pathogenesis of Psoriasis
Survival, Activation, and Proliferation of T Cells
Different T cell subtypes have different metabolic preferences. For example, T memory (Tm) cells initiate de novo synthesis of fatty acids and utilize lysosomal acidic lipase (LAL)-dependent fatty acid b-oxidation. Fatty acids also regulate the activation of immune cells and binding to specific receptors. After stimulation by certain ligands, metabolism shifts, and supplementation with arginine can inhibit glycolysis and reduce inflammation.
Differentiation of T Cells
Short- and medium-chain fatty acids can affect the differentiation of T helper (CD4+) cells. They can downregulate histone deacetylase activity and activate the mTOR pathway. Fatty acids and their metabolites can also activate different cell signal transduction pathways by binding peroxisome proliferator-activated receptors (PPARs), which are important for the differentiation of several T cell subsets.
Migration of Immune-Associated Cells
Direct exposure to palmitate can lead to abnormal expansion of proinflammatory effector and memory lymphocyte populations in obese patients. Unsaturated fatty acids can reduce the number of effector and memory CD4+ cells and inhibit their migration. Sphingol-1-phosphate (S1P) is associated with T cell migration, and each of its receptors plays a unique role. Ceramides can monitor neutrophil function and block respiratory bursts.
Influence on the Inflammation-Associated Signaling Pathway
LPC can activate transcription factors and increase the expression of target genes to activate inflammatory signaling pathways. Ceramide plays an important role in DC activation, inducing apoptosis and promoting the production of proinflammatory cytokines. Excess circulating amino acids can stimulate the mTOR/S6 kinase (S6K) pathway, which may contribute to the development and maintenance of chronic inflammation. Short-chain fatty acids have therapeutic potential for psoriasis.
Effects of Metabolite Transporters
Transporters are proteins that transport metabolic substrates across cell membranes. They can affect metabolite levels, metabolic balance, and immunity. For example, GLUT1 is the major GLUT in T cells and plays a regulatory role in their activation and differentiation. Increased expression of L-type amino acid transporter 1 (LAT1) in psoriatic lesions has been detected, and its inhibition can prevent the proliferation of certain T cells and control signal transduction.
Limitations and Expectations
Potential for Clinical Application
Metabolomics has shown great potential in clinical applications for psoriasis, such as diagnosis, treatment, and prognosis. For example, the levels of certain amino acids and metabolites in serum and psoriatic lesions are associated with the severity of psoriasis. Changes in metabolite profiles after treatment can also indicate the efficacy of the treatment. Different biological agents may have different effects on metabolite profiles, suggesting different mechanisms.
Limitations
Currently, metabolomics research still faces some challenges. Compound identification is a problem due to the complexity of biological samples and metabolites. The development of metabolomics is also constrained by the lack of functional metabolite databases and uniform research standards. The link between metabolomics data and biomedicine can be easily confused, and some biomarkers are generic for inflammation-related diseases. The clinical application of metabolomics also requires validation by orthogonal analysis techniques.
Future Integrated “-omics” Approaches
To understand the effects of metabolism alterations on psoriasis at a holistic level, integrating metabolomics with other “-omics” such as proteomics and genomics is necessary. New models such as mergeomics and skinomics are emerging, emphasizing the concept of “systematic” and “holistic” in psoriasis research. Metabolomics can assist in developing new therapeutic targets, and its evolution with new technologies, such as single-cell analysis and stable isotope tracers, will further clarify metabolic networks in disease.
Conclusions
There is a growing interest in using metabolomics techniques in psoriasis treatment development. Metabolomics provides in-depth information about the association between metabolic state and disease, which is crucial for developing individualized therapies. As metabolomics technology continues to evolve and our understanding of metabolic disorders deepens, more diagnostic and therapeutic targets are expected to emerge and be translated into clinical practice.
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