Serum Fatty Acid-Binding Protein 4 Is Increased in Patients with Psoriasis
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Lipids DOI 10.1007/s11745-016-4211-4 ORIGINAL ARTICLE Serum Fatty Acid-Binding Protein 4 is Increased in Patients with Psoriasis A. Baran1 · M. S´widerska2 · Joanna Bacharewicz-Szczerbicka1 · H. Mys´liwiec1 · I. Flisiak1 Received: 4 August 2016 / Accepted: 2 November 2016 © The Author(s) 2016. This article is published with open access at Springerlink.com Abstract Psoriasis is associated with metabolic syndrome ml] (p 0.12), losing its basal significance. FABP4 may be = and cardiovascular disease. Fatty acid-binding proteins a marker of psoriasis, and FABP3 may be associated with (FABP) have been recognized as predictors of these sys- inflammation or liver disorders in psoriatic patients. FABP temic disorders. The aim of this study was to assess cor- do not appear to be useful for determining disease severity relations between levels of serum heart and adipocyte or the effectiveness of antipsoriatic treatment. fatty acid-binding proteins (FABP3, FABP4) and disease severity, indicators of inflammation or metabolic distur- Keywords Psoriasis · Fatty acid-binding protein 3 · bances, and topical treatment in psoriatic patients. Thirty- Fatty acid-binding protein 4 · Anthralin · Lipids · seven patients with relapse of plaque-type psoriasis and Metabolic syndrome 16 healthy volunteers were recruited. Blood samples were collected before and after 14 days of therapy. Serum FABP Abbreviations concentrations were examined by enzyme-linked immu- aP2 Adipocyte protein 2 nosorbent assay for correlation with Psoriasis Area and BMI Body mass index Severity Index (PASI), body mass index (BMI), inflam- CAD Coronary artery disease matory or metabolic parameters, and treatment used. The CRP C-reactive protein median FABP4 serum levels were significantly increased DM Diabetes mellitus (p 0.038) in psoriatic patients, while FABP3 levels did ELISA Enzyme-linked immunosorbent assay = not differ (p 0.47) compared to the controls. No sig- FA Fatty acids = nificant correlations were noted between the proteins and FABP Fatty acid-binding proteins PASI, C-reactive protein (CRP), BMI, or levels of glu- FABP1 Liver fatty acid-binding protein cose or lipids. FABP3 significantly correlated with white FABP3 Heart fatty acid-binding protein blood count (p 0.03) and aspartate aminotransferase FABP4 Adipocyte fatty acid-binding protein = (p 0.04). After topical treatment, there was no significant FABP5 Epidermal fatty acid-binding protein = change in serum FABP3 [11.5 (4.9–30.3) vs. 12.9 (3.5– HDL-C High-density lipoprotein cholesterol 30.3) ng/ml] (p 0.96), whereas FABP4 was decreased IR Insulin resistance = [27,286 (20,344–32,257) vs. 23,034 (18,320–29,874) pg/ L-FABP Liver fatty acid-binding protein LCFA Long-chain fatty acids * A. Baran LDL-C Low-density lipoprotein cholesterol [email protected] MI Myocardial infarction MS Metabolic syndrome 1 Department of Dermatology and Venereology, Medical NAFLD Non-alcoholic fatty liver disease University of Bialystok, Zurawia 14 St, 15‑540 Bialystok, Poland NB-UVB Narrow-band ultraviolet B PA-FABP Psoriasis-associated fatty acid-binding protein 2 Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Zurawia 14 St, 15‑540 Bialystok, PASI Psoriasis Area and Severity Index Poland PLT Platelets 1 3 Lipids RBC Red blood count named based on the tissues in which they are prominently RBP-4 Retinol-binding protein 4 expressed or those that actively participate in lipid metabo- SR Sedimentation rate lism: liver, intestines, heart, adipose tissue, epidermis, ileus, TAG Triacylglycerol brain, myelin and testis. FABP isoforms are thought to be TNF-α Tumor necrosis factor-α useful indicators of organ damage and to play an important VEGF Vascular endothelial growth factor role in the development of a number of systemic diseases. WBC White blood cell FABP1 (liver FABP), present mainly in hepatocytes and excreted by the kidneys, indicates acute kidney damage and liver disorders, while the ileal isoform may be associated Introduction with ileitis or IR [10]. Epidermal fatty acid-binding protein 5 (FABP5), with its Psoriasis is a chronic inflammatory dermatosis with a mul- gene located at chromosome 8q21.13, is mostly expressed tifactorial pathogenesis, affecting over 2% of the world’s in epidermal cells, but also in other tissues including the population. Recently it has been considered as a systemic brain, kidney, liver, lungs, and testis and in adipose tissue. disorder closely associated with coronary artery disease Various studies have stressed its role in regulating insulin (CAD), hypertension, diabetes mellitus (DM), obesity, sensitivity, lipid homeostasis, MS, skin barrier conditions, metabolic syndrome (MS) and atherosclerosis [1, 2]. Pso- and even nerve regeneration [8, 10, 12, 13]. FABP5 is riatic patients live on average 5 years less than the general also called psoriasis-associated FABP (PA-FABP), which population, which is due to increased risk of myocardial reflects its already proven links with this dermatosis [12, infarction (MI) and thromboembolic events [3]. The risk 13]. Some studies have indicated that FABP5 modulates of developing DM, obesity and MS is more than double, the differentiation of keratinocytes and is highly over- occurring in over 40% of psoriatic patients [4]. Com- expressed in psoriatic plaques or atopic dermatitis [12, 13]. mon links between psoriasis and its comorbidities mainly Heart-type FABP (FABP3), with the encoding gene involve the chronic inflammation that emerges from meta- located on chromosome 1p33–p31, is expressed mainly bolic tissues (metaflammation), genetic basis, similar path- in the heart, skeletal muscle, brain, mammary glands and ways of immune disorders, and bioactive substances syn- brown adipose tissue. FABP3 is superior to troponin as a thesized and secreted by adipose tissue [4–6]. Numerous highly sensitive marker of acute myocardial infarction and published studies, as well as ours, have demonstrated the predictor of heart failure in patients with MS, which is potential role of various adipokines in the development of strongly associated with psoriasis [8, 10]. FABP3 also par- psoriasis and its comorbidities [5, 7]. ticipates in thermoregulation and affects glucose homeosta- Lipids, such as fatty acids (FA) and their derivatives, sis and cardiac sufficiency [9, 10]. A precise role of FABP3 perform various biological functions, including their role in other tissues and the development of certain diseases is in energy homeostasis, the formation of substrates for cell still largely unknown. membranes, and signaling molecules in inflammatory and Adipocyte fatty acid-binding protein (FABP4), also metabolic pathways [8]. Disturbances in lipid homeostasis termed adipocyte protein 2 (aP2), is an adipokine synthe- can lead to numerous common disorders including obesity, sized and released predominantly from adipocytes and, to insulin resistance (IR), DM, cardiovascular disease, and a lesser extent, produced in macrophages and endothelial even skin disorders [9, 10]. Fatty acids, which constitute cells [6, 14]. FABP4, with a molecular mass of 14.6 kDa about 15% of lipids in the stratum corneum, participate in and 132 amino acids, accounts for up to 6% of total cellu- maintaining the permeability of the epidermis, for example, lar proteins. The gene encoding this adipokine is located on by stimulating acidification of the horny layer. Research chromosome 8q21. Elevated levels of FABP4 are closely has shown that deviations in FA composition in keratino- linked with the development of obesity, IR, DM, hyper- cytes may be involved in the pathogenesis of inflammatory tension, CAD and atherosclerosis [10, 14, 15]. Studies in dermatosis such as atopic dermatitis or psoriasis [11]. FA humans have shown that a genetic variant at the FABP4 shifted to long-chain fatty acids (LCFA) are transported by locus reduced the risk for atherosclerosis, diabetes and cor- certain proteins to various tissues, where they are metabo- onary heart disease [16, 17], and reduced FABP4 expres- lized, stored or utilized [9]. Fatty acid-binding proteins sion in adipose tissue was related to lower risk for CAD (FABP), first identified in 1972, are a 14–15 kDa family and DM [16]. Several studies have proved that increased of cytosol proteins involved in active regulation of lipid circulating FABP4 levels are a promising biomarker pre- trafficking and the protection of organisms against harm- dicting heart failure, stroke, and prognosis and mortality in ful accumulation of LCFA [8, 10, 11]. To date, at least patients with end-stage renal disease, CAD or other critical nine isoforms have been identified, and they have been illnesses [6, 14, 15, 20, 21]. 1 3 Lipids Another possible role of FABP4 in psoriasis is evident in Serum Collection the influence on MS, which is strongly associated with pso- riasis. FABP4 is an independent predictive marker for the Blood samples were collected from the study and control development of MS, as was shown in a 5-year prospective groups using Vacutainer tubes, and were left for 30 min to study and in a study of Korean boys [18, 19]. allow clotting before centrifugation for 15 min at 1000g, A further link between FABP4 and psoriasis may be a after which the serum was separated and stored at 80 °C − correlation with tumor necrosis factor-α (TNF-α), which is until use. FABP3 and FABP4 levels were measured using one of the major cytokines involved in the pathogenesis of the Quantikine® enzyme immunoassay kit (R&D Sys- this dermatosis. FABP4-deficient macrophages