BIOCHEMICAL PATHWAYS OF METABOLIC DISORDERS IN PSORIASIS

Abstract

The development of metabolic disorders occurs in psoriasis: insulin resistance, systemic inflammation, atherosclerosis, oxidative stress and obesity. The paper presents pathological biochemical pathways of metabolic disorders development which is caused by common cytokine profile characteristic for psoriasis and obesity and they are tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8). The following links play a role in the development of insulin resistance: insulin receptor (IRS-1) and insulin receptor substrate (SIR-1), glucose transporter protein (GLUT-4), also there is a decrease in the phosphatidylinositol 3-kinase pathway (PI3AKT) activity, and an increase in the mitogen activating protein kinase (MAPK) activity. Factors influencing the development of inflammation are discussed: IL-6, C-reactive protein, tissue plasminogen activator inhibitor (PAI-1), monocyte chemoattractant protein 1 (MCP-1), proinflammatory adipokines; processes of vascular inflammation development, atherosclerosis development and oxidative stress. This article discusses endocrine disruption of adipocytes in obesity and the influence of adipokines and inflammatory mediators synthesized by fat cells on psoriatic disease. Advanced glycation end products (AGEs), hyperhomocysteinemia (HHcy) due to vitamin B12 and folic acid deficiency, and a 5,10-methylfolate reductase (MTHFR) mutation are also important in the clinical manifestations of psoriasis. The possibility of assessing metabolic disorders and dysfunction of various organs by changes in the levels of metabolites in the blood and skin of patients with psoriasis is discussed.

Keywords

• adipocyte
• adipokine
• vitamin b12
• vitamin d
• inflammation
• insulin resistance
• metabolomics
• oxidative stress
• end-glycation products
• psoriasis
• folic acid