leptin and Psoriasis

Psoriasis is a chronic and immune-mediated skin condition characterized by pro-inflammatory cytokines and keratinocyte hyperproliferation. Dendritic cells, T lymphocytes, and keratinocytes represent the main cell subtypes involved in the pathogenesis of psoriasis, while the interleukin-23 (IL-23)/IL-17 pathway enhances the disease progression. Human adipose tissue is an endocrine organ, which secretes multiple proteins, known as adipokines, such as adiponectin, leptin, visfatin, or resistin. Current evidence highlights the immunomodulatory roles of adipokines, which may contribute to the progression or suppression of psoriasis. A better understanding of the complexity of psoriasis pathophysiology linked with adipokines could result in developing novel diagnostic or therapeutic strategies. This review aims to present the pathogenesis of psoriasis and the roles of adipokines in this process.

Topics: Adipokines; Adiponectin; Adipose Tissue; Humans; Leptin; Psoriasis; Resistin

In obesity, adipocytes are dysfunctional with excessive production and secretion of pro-inflammatory hormones and cytokines, ie, adipokines, such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and leptin. Accumulating evidence has shown that leptin possesses pleiotropic functions including stimulation of angiogenesis and production of pro-inflammatory cytokines. Furthermore, various leptin associated activities involve a wide distribution of leptin receptors. For example, increased serum leptin was associated with tissue receptor resistance in metabolic syndrome. Although increased serum leptin, receptor and signaling impairment are involved in wound healing, hair cycle and the pathogenesis of many skin diseases such as psoriasis and lupus erythematosus as well as skin cancer, its exact role remains unclear. In the present article, we discuss the biochemistry of leptin action and its potential role in the pathophysiology of diverse skin diseases.

Topics: Adipocytes; Adipokines; Cytokines; Humans; Leptin; Psoriasis; Tumor Necrosis Factor-alpha

Leptin is an adipokine, adipocyte-derived compound, which acts both as a hormone and cytokine. It is mainly synthesized by adipocytes of white adipose tissue. Leptin possesses pleiotropic functions including, among others, stimulation of angiogenesis and production of proinflammatory cytokines. The various types of leptin activity are related to the wide distribution of leptin receptors. This adipokine acts by activating intracellular signaling cascades such as JAKs (Janus kinases), STATs (signal transducers and activators of transcription), and others.In a course of obesity, an increased serum level of leptin coexists with tissue receptor resistance. It has been reported that enhanced leptin levels, leptin receptor impairment, and dysfunction of leptin signaling can influence skin and hair. The previous studies revealed the role of leptin in wound healing, hair cycle, and pathogenesis of skin diseases like psoriasis, lupus erythematosus, and skin cancers. However, the exact mechanism of leptin's impact on the skin is still under investigation. Herein, we present the current knowledge concerning the role of leptin in psoriasis and selected skin diseases.

Topics: Adipocytes; Adipokines; Adipose Tissue; Animals; Humans; Janus Kinases; Leptin; Lupus Erythematosus, Cutaneous; Psoriasis; Receptors, Leptin; Signal Transduction; Skin Diseases; Skin Neoplasms; STAT Transcription Factors

Psoriasis is a chronic, systemic, hyper-proliferative immune-mediated inflammatory skin disease. The results of epidemiological investigations have shown that psoriasis affects around 2% of the general population worldwide, and the total number of psoriasis patients is more than 6 million in China. Apart from the skin manifestations, psoriasis has been verified to associate with several metabolic comorbidities, such as insulin resistance, diabetes and obesity. However, the underlying mechanism is still not elucidated. Adipocytes, considered as the active endocrine cells, are dysfunctional in obesity which displays increased synthesis and secretion of adipokines with other modified metabolic properties. Currently, growing evidence has pointed to the central role of adipokines in adipose tissue and the immune system, providing new insights into the effect of adipokines in linking the pathophysiology of obesity and psoriasis. In this review, we summarize the current understanding of the pathological role of adipokines and the potential mechanisms whereby different adipokines link obesity and psoriasis. Furthermore, we also provide evidence which identifies a potential therapeutic target aiming at adipokines for the management of these two diseases.

Topics: Adipocytes; Adiponectin; Adipose Tissue; Cytokines; Gene Expression Regulation; GPI-Linked Proteins; Humans; Immune System; Immunologic Factors; Interleukin-1beta; Interleukin-6; Lectins; Leptin; Molecular Targeted Therapy; Obesity; Psoriasis; Signal Transduction; Tumor Necrosis Factor-alpha

Psoriasis is a common chronic inflammatory multisystemic disease with a complex pathogenesis consisting of genetic, immunological, and environmental components. It is associated with a number of comorbidities, including diabetes, metabolic syndrome, obesity, and myocardial infarction. In addition, the severity of psoriasis seems to be related to the severity of obesity. Patients with higher levels of obesity show poorer response to systemic treatments of psoriasis. Several studies have demonstrated that white adipose tissue is a crucial site of the formation of proinflammatory adipokines such as leptin, adiponectin, and resistin and classical cytokines such as interleukin- (IL-) 6 and tumour necrosis factor-

Topics: Biomarkers; Humans; Inflammation; Leptin; Obesity; Psoriasis; Resistin

Metabolic syndrome, a risk factor of cardiovascular disease, is more common in patients with psoriasis than in the general population. Circulating adipokine concentrations are altered in patients with psoriasis and are suggested to represent the pathophysiological link between psoriatic lesions and metabolic alterations.. To perform a systematic review of the literature for studies that investigated possible differences in circulating levels of leptin, adiponectin or resistin in patients with psoriasis before and after any treatment intervention, and to meta-analyse the best evidence available.. A search was conducted in three databases (PubMed, Central and Embase). Eligible for the review were studies that assessed leptin, adiponectin or resistin concentrations in patients with psoriasis before and after any topical or systemic treatment.. After treatment, blood concentrations of leptin were similar to those before treatment [standardized mean difference (SMD) 0·06, 95% confidence interval (CI) -0·09 to 0·20], with no heterogeneity among studies (I. There is no evidence that treatment for psoriasis modifies leptin and adiponectin concentrations. However, treatment intervention reduces resistin concentrations, a finding that is expected to be of clinical importance.

Topics: Adiponectin; Dermatologic Agents; Humans; Leptin; Metabolic Syndrome; Psoriasis; Resistin; Treatment Outcome

Psoriasis usually combines with metabolic diseases,and the prevalence of cardiovascular disease remarkably increases in psoriatic patients. Adipokines,which play an important role in the cardiovascular diseases,also express abnormally in psoriasis and may induce or exacerbate the skin lesion. The adipokines associated with psoriasis and cardiovascular disease include adiponectin,leptin,resistin,omentin,visfatin,chemerin,and retinoid binding protein 4 (RBP-4). The levels of adiponectin and omentin apparently decrease in psoriatic patients compared to healthy controls,and thus they may play protective roles for psoriasis. Similarly,adiponectin plays a protective role in cardiovascular disease,but the role of retina in cardiovascular disease is still controversial. However,the concentrations of leptin,resistin,visfatin,chemerin,and RBP-4 in patients with psoriasis or cardiovascular disease are significantly higher than those of the controls;therefore,they may serve as the pathogenic factors for both diseases. Low adiponectin,leptin,visfatin,and chemerin levels may induce or aggravate psoriasis by activating plasmacytoid dendritic cells or T cells,as demonstrated in in vitro experiments. However,in vitro experiments also have shown that visfatin may inhibit cardiomyocyte apoptosis.

Topics: Adipokines; Adiponectin; Apoptosis; Cardiovascular Diseases; Chemokines; Cytokines; Dendritic Cells; GPI-Linked Proteins; Humans; Intercellular Signaling Peptides and Proteins; Lectins; Leptin; Myocytes, Cardiac; Nicotinamide Phosphoribosyltransferase; Psoriasis; Resistin; Retinol-Binding Proteins, Plasma; T-Lymphocytes

This article describes premises for the development of psychodermatology. An analysis of research literature and data is presented based on the example of psoriasis and anxiety disorder. Protein molecules with altered concentrations in patients with psoriasis and anxiety disorder compared to controls are identified (chemokine [C-C motif] ligand 2, corticotropin-release hormone, growth hormone 1, leptin, and tumor necrosis factor with increased concentration and brain-derived neurotrophic factor with decreased concentration). All molecules are secretory peptides. In the future, the information obtained may make it possible to pursue an in-depth study of the molecular mechanisms underlying psychodermatology.

Topics: Anxiety Disorders; Brain-Derived Neurotrophic Factor; Corticotropin-Releasing Hormone; Growth Hormone; Humans; Leptin; Psoriasis; Tumor Necrosis Factor-alpha

Epidemiological studies suggest an increased prevalence of cardiovascular disease (CVD) in patients with psoriasis (PS). Therefore, emphasis has lately been laid on the necessity for clinical evaluation of the risk of CVD in these patients. The systemic inflammatory markers C-reactive protein (CRP) and interleukin- (IL-) 6, which have long been used to predict future CVD in the general population, are increased manyfold in patients with PS. Lipid abnormalities characterized by elevated triglycerides, low HDL cholesterol, and higher concentrations of LDL cholesterol and its oxidized form are also prevalent in patients. There is a need for additional laboratory markers for the assessment of cardiovascular status of patients with PS. Due to frequent comorbid overweight and obesity, biologically active compounds produced by adipocytes may have an impact on monitoring the status of the cardiovascular system of patients with PS. For this purpose, two adipokines, adiponectin and leptin, have been most extensively studied. The review focuses on some inflammatory and oxidative stress aspects in patients with PS through the analysis of the impact of prominent adipokines and oxidized low-density lipoprotein (oxLDL) to assess their eligibility for clinical practice as markers of CVD risk in patients with PS.

Topics: Adipokines; Animals; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Humans; Interleukin-6; Leptin; Lipoproteins, LDL; Psoriasis; Risk Factors

Psoriasis is an immune-mediated, inflammatory disease. Adipokines contribute to the regulation of immune-mediated processes and inflammation.. The aim of our study was to systematically review the literature for studies that have evaluated the circulating concentrations of adipokines in patients with psoriasis and controls and to meta-analyze the best evidence available.. Eligible were studies that have assessed leptin, resistin, or adiponectin concentrations in psoriatic patients and a reference group. The study was conducted in adherence with the PRISMA standards.. Psoriatic patients had higher leptin concentrations compared to controls (random effects model, mean difference, MD = 5.64 ng/mL, 95% CI: 3.00-8.29, p < 0.0001). Heterogeneity among studies was high (I2 = 95.9%). Psoriatic patients had higher resistin concentrations compared to controls (MD = 4.66 ng/mL, 95% CI: 2.62-6.69, p < 0.0001). Heterogeneity was high (I2 = 99.2%). Finally, psoriatic patients had lower adiponectin concentrations compared to controls (MD = -1.87 μg/mL, 95% CI: -2.76 to -0.98, p < 0.0001). Heterogeneity was high (I2 = 95.9%).. The study supported the hypothesis that leptin and resistin concentrations are higher and adiponectin concentrations are lower in patients with psoriasis compared to controls. Hereby, the suggested pathogenic link between psoriasis and metabolic syndrome/obesity is reinforced and the role of comorbidities in psoriasis is highlighted.

Topics: Adiponectin; Biomarkers; Humans; Leptin; Observational Studies as Topic; Psoriasis; Resistin

There have been inconsistent results reported for leptin levels in patients with psoriasis.. To evaluate leptin levels in patients with psoriasis using a meta-analysis of studies comparing leptin levels in controls and in patients with psoriasis.. PubMed (MEDLINE), EMBASE and the Cochrane Library were searched for relevant papers published in English. Pooled weighted mean differences (WMDs) and 95% CIs were calculated using random-effects and fixed-effects models. Heterogeneity between studies was assessed using the Cochran Q and I(2) statistics.. In total, 11 studies, comprising 773 patients with psoriasis and 570 healthy controls, were identified. Leptin levels were significantly higher in patients with psoriasis compared with controls (WMD = 7.24, 95% CI 4.55-9.93; P < 0.001). On stratified analysis, significant differences in leptin levels between patients with psoriasis and controls were reported only in serum samples (P < 0.001), and not in plasma samples (P = 0.025). Sensitivity analysis showed that there were no changes in the direction of effect when any one study was excluded. No publication bias was detected.. Leptin levels are higher in patients with psoriasis compared with those in controls. Future studies are warranted to clarify the association between leptin levels and the pathomechanism of psoriasis.

Topics: Biomarkers; Humans; Leptin; Psoriasis; Risk Factors

After an initial attempt by the WHO to define metabolic syndrome (MS) on a pathophysiologically oriented approach requiring the assessment of insulin resistance markers, the NCEP-ATPIII and more recently the IDF proposed more clinically oriented criteria to help, toward a preventive medicine goal, to identify patients who are likely to have features of the MS and be at increased risk of type 2 diabetes and cardio vascular disease. The notion of MS is built around abnormalities of the metabolism of lipids and carbon hydrates, a rise of blood pressure, and visceral obesity of abdominal localization. These parameters report only partially on mechanisms leading to the development of the MS. The physiopathology of MS is partially understood even today and likely results from the combination of environmental, genetic and epigenetic factors. Abdominal visceral obesity, a state of low-grade chronic inflammation and insulin resistance are the main processes susceptible to explain the various constituents of this syndrome.

Topics: Environment; Exercise; Humans; Hypertension; Inflammation; Insulin Resistance; Leptin; Metabolic Syndrome; Models, Biological; Nutritional Status; Psoriasis

To investigate the effects of acitretin treatment on insulin resistance (IR) and adipokines, particularly retinol-binding protein (RBP)-4.. Thirty-four patients with chronic plaque psoriasis and a control group of 34 healthy volunteers were recruited in the study. Screening for the parameters was performed before starting and after 3 months of acitretin treatment in the psoriasis group. The control group was only evaluated at the beginning of the study and did not receive placebo. We could not compare our results with a placebo control group because of ethical reasons.. Basal adiponectin (p = 0.01), insulin (p < 0.0001) levels and homeostasis model assessment (HOMA) IR (p < 0.0001) were significantly higher in psoriasis patients. After the treatment, insulin (p = 0.014), C peptide (p = 0.011), RBP-4 (p < 0.0001) levels and HOMA-IR (p = 0.008) decreased significantly. Posttreatment leptin (p = 0.036) levels were significantly lower than those of the controls. Posttreatment adiponectin (p = 0.005) and insulin (p = 0.048) levels were higher than those of the controls.. This study showed for the first time that RBP-4 levels and IR are decreased significantly with acitretin treatment. This finding is very important in psoriasis patients because psoriasis may cause insulin resistance and diabetes. Further experimental and clinical studies are needed to clarify the effect of acitretin on adipocyte structure and behavior.

Topics: Acitretin; Adiponectin; Adult; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Insulin; Insulin Resistance; Leptin; Male; Psoriasis; Retinol-Binding Proteins, Plasma

Patients with moderate-to-severe plaque-type psoriasis exhibit increased cardiovascular mortality. Recent publications point towards psoriasis-induced insulin resistance as an important pathomechanism driving cardiovascular comorbidity in these patients. As the hormonal status in general and sex hormone-binding globulin (SHBG) in particular serve as sensitive indicators for insulin resistance, we analysed these parameters in the context of a set of multiple additional clinical and laboratory measurements in a cohort of male patients. Of 33 consecutively enrolled male patients receiving continuous systemic therapy for their moderate-to-severe plaque-type psoriasis, 23 male patients for whom all parameters could be collected over a 24-week treatment period were included in this analysis. At baseline, testosterone levels varied between 212 and 660 ng/ml (median: 377.0), and SHBG between 11.9 and 46.0 nmol/l (median: 29.2), thus documenting lack of hypogonadism among these patients. Clinically, 19/23 patients experienced at least a 50% reduction in their PASI under therapy. Using a multivariate regression model to further analyse the sub-group of patients responding to treatment, hs-CRP, PASI, leptin and resistin all improved under effective systemic anti-inflammatory therapy, thus losing their significant influence on SHBG. SHBG performed well as a sensitive biomarker for insulin resistance and systemic inflammation in these patients. Its improvement, as well as the reduction of resistin serum levels, most likely reflects a state of reduced cardiovascular risk in patients undergoing effective continuous systemic therapy. Long-term safety data, generated e.g. from psoriasis registries, are needed to assess whether this effect translates into reduced cardiovascular mortality.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Disease Progression; Follow-Up Studies; Humans; Inflammation; Insulin Resistance; Leptin; Male; Middle Aged; Pilot Projects; Prospective Studies; Psoriasis; Resistin; Risk; Sex Hormone-Binding Globulin; Testosterone

Patients with psoriasis are frequently complicated with metabolic syndrome; however, it is not fully understood how obesity and dyslipidemia contribute to the pathogenesis of psoriasis. To investigate the mechanisms by which obesity and dyslipidemia exacerbate psoriasis using murine models and neonatal human epidermal keratinocytes (NHEKs), we used wild-type and

Topics: Animals; Dermatitis; Dyslipidemias; Humans; Inflammation; Interleukin-17; Keratinocytes; Leptin; Mice; Obesity; Palmitic Acid; Psoriasis; Skin; Tumor Necrosis Factor-alpha

Psoriasis is a chronic inflammatory disease associated with obesity and metabolic syndrome. Adipokines are thought to be a link between psoriasis and obesity. Leptin, adiponectin, and omentin are bioactive adipokines thought to play a role in both metabolic comorbidities and inflammation. Anti-tumour necrosis factor alfa (anti-TNF-α) agents are effective for psoriasis treatment, although significant weight gain has been reported during anti-TNF-α therapy. The interleukin 12/23 (IL 12/23) inhibitor ustekinumab is also effective for psoriasis treatment. We compared the effects of three anti-TNF-α drugs and an IL-12/23 inhibitor on adipokines and weight gain during treatment.. This prospective study included 80 patients (37 women, 43 men) with moderate to severe plaque psoriasis whose age and weight were matched. The patients were divided into four equal groups: etanercept, infliximab, adalimumab, and ustekinumab treatment groups. Psoriasis Area Severity Index (PASI) score, body weight (muscle and fat compartments), and leptin, adiponectin, and omentin levels were evaluated at baseline and weeks 4, 12, 24, and 48 of treatment.. There were no differences between drug groups in terms of weight parameters or biochemical parameters at baseline. At the end of 48 weeks, there was significant weight gain in the adalimumab group. Patients who received infliximab showed significant weight gain by week 12, but in the following weeks they returned to their initial weight. Body weight reached a maximum level by week 12 in patients using etanercept, but they lost weight in the following weeks and finished the study below their initial weight. Patients using ustekinumab did not demonstrate significant weight change during the 48 weeks except at week 12. At the end of week 48, PASI75 (improvement in PASI ≥75%) response rates were approximately 85% for the ustekinumab group, 80% for the adalimumab group, 75% for the infliximab group, and 50% for the etanercept group. Leptin, adiponectin, and omentin levels were higher in the ustekinumab group at all weeks except baseline. The lowest levels were observed in the etanercept group. The treatment response rate was also lower in the etanercept group.. We did not evaluate visfatin and resistin levels, insulin sensitivity, and cardiovascular risk that may be associated with weight gain and adipokine levels.. Unlike TNF inhibitors, ustekinumab does not cause significant weight changes and it increases adipokine levels more than TNF inhibitors. Adipokine levels seem to be related to the treatment response.

Topics: Adalimumab; Adipokines; Adiponectin; Body Weight; Etanercept; Female; Humans; Infliximab; Interleukin-12; Interleukin-23; Leptin; Male; Obesity; Prospective Studies; Psoriasis; Severity of Illness Index; Tumor Necrosis Factor Inhibitors; Ustekinumab; Weight Gain

Fat mass distribution, especially in the abdominal visceral region, has been rarely evaluated in patients with PsA or psoriasis (PsO).. Patients with PsA and patients with PsO alone were evaluated and compared with control subjects (1:1 ratio in each patient group) matched for age, sex and BMI category. Body composition and fat distribution (android and visceral fat) were evaluated by DXA. Anthropometric measurements, disease activity and the systematic coronary risk evaluation (SCORE) cardiovascular risk were assessed. Metabolic parameters (insulin, homeostasis model assessment for insulin resistance), serum adipokines [total and high-molecular-weight adiponectin, leptin, resistin and retinol-binding protein-4 (RBP4)] were measured.. Data for 52 patients with PsA and 52 patients with PsO and their respective paired controls were analysed. Android fat and visceral fat were found to be significantly higher in patients with PsO compared with their controls, while these measurements did not differ between patients with PsA and their controls. By multivariate analysis, after adjusting for age, sex and BMI, visceral fat was higher in PsO patients compared with PsA patients (P = 0.0004) and the whole group of controls (P = 0.0013). Insulin levels and HOMA-IR were increased in both PsA and PsO groups. High-molecular-weight/total adiponectin ratio was decreased in patients with PsO. RBP4 was significantly higher in both PsA and PsO patients. In patients with PsO, visceral fat strongly correlated with SCORE (r = 0.61).. Visceral fat accumulates more in PsO alone than in PsA. Visceral adiposity may be a more pressing concern in PsO relative to PsA.. The ADIPSO study (Évaluation du tissu ADIpeux et des adipokines dans le PSOriasis et le rhumatisme psoriasique et analyse de ses relations avec le risque cardiovasculaire) is a case-control study conducted in Besançon, France, and is registered on ClinicalTrials.gov under the number NCT02849795.

Topics: Adipokines; Age Factors; Arthritis, Psoriatic; Body Composition; Body Mass Index; Case-Control Studies; Female; Heart Disease Risk Factors; Humans; Insulin; Insulin Resistance; Intra-Abdominal Fat; Leptin; Male; Middle Aged; Multivariate Analysis; Obesity, Abdominal; Psoriasis; Resistin; Retinol-Binding Proteins, Plasma; Sex Factors

Psoriasis is a disease with a proinflammatory base, in which an increased expression of leptin, tumor necrosis factor alpha (TNF-α), interleukin (IL) IL-12/23, IL-6, is observed. A drug used in the treatment of psoriasis of moderate and acute strength is the monoclonal antibody anti-TNF-adalimumab. The goal of this study was to evaluate the influence of adalimumab on changes in the expression profile of leptin-related genes in human keratinocyte cells exposed to lipopolysaccharide A and analyze if adalimumab acts via leptin pathways. The evaluation of changes of the pattern of genes connected with leptin and proteins coded by them was marked in a culture of human keratinocytes (HaCaT) exposed to 1 µg/mL lipopolysaccharide A (LPS) for 8 h in order to induce the inflammatory process, then to 8 µg/mL of adalimumab for 2.8 and 24 h in comparison with the control (cells not treated with the substances). The techniques used were mRNA microarray, Real-Time Quantitative Reverse Transcription Reaction (RTqPCR), Enzyme-Linked Immunosorbent Assay (ELISA), as well as transfections of HaCaT culture with leptin small interfering RNA (siRNA) in order to see whether adalimumab works through pathways dependent on leptin. A statistically lower expression of leptin and its receptors was observed under the influence of the drug, independent of the exposition time of keratinocytes to adalimumab. In the cells transfected with leptin siRNA, a lower concentration of JAK2 and STAT3 proteins was observed, which confirms that adalimumab works through pathways dependent on leptin. Adalimumab has a modulatory effect on the gene expression pattern and the proteins coded by them connected with leptin in keratinocytes treated with LPS in vitro.

Topics: Adalimumab; Anti-Inflammatory Agents; Caspases; Cell Line; Humans; Keratinocytes; Leptin; Lipopolysaccharides; Psoriasis; Receptors, Leptin; RNA, Messenger; RNA, Small Interfering; Signal Transduction; Transcriptome; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha

Topics: Caveolin 1; Cells, Cultured; Humans; Inflammation; Interleukin-6; Interleukin-8; Keratinocytes; Leptin; Obesity; Psoriasis

Topics: Adalimumab; Anti-Inflammatory Agents; Cells, Cultured; Fibroblasts; Gene Expression; Humans; Interleukin-12; Interleukin-23; Interleukin-6; Leptin; MicroRNAs; Psoriasis; Receptors, Notch; RNA, Messenger; Signal Transduction; Transcription Factor HES-1; Transcription, Genetic

Adipokines have been considered in the pathogenesis of the inflammatory processes of psoriatic arthritis (PsA). The main aim of the current study is to investigate possible differences and correlations between adipokines and clinical expression in PsA patients with and without clinical evident psoriasis.. Serum levels of TNF-α, IL-6, leptin, resistin, visfatin, and ghrelin were measured in 80 consecutive PsA patients, 42 PsA patients with clinically evident psoriasis (group 1) and 38 PsA patients sine psoriasis (group 2), fulfilling the CASPAR criteria.. Patients of the two groups were not significantly different for levels of TNF-α, IL-6, leptin, resistin, visfatin, and ghrelin. In the entire cohort, a positive association has been shown between leptin levels and female gender (β = 0.3, p = 0.001), BMI (β = 0.8, p < 0.0001), tender joint count (β = 0.23, p = 0.05), and patient pain-VAS score (β = 0.4, p = 0.049). In group 1, serum concentration of leptin was associated with female gender (β = 0.41, p < 0.0001) and BMI (β = 0.6, p = 0.012), whereas in group 2, a positive association was shown between leptin levels and BMI (β = 0.7, p = 0.003) and CRP (β = 0.35, p = 0.012). With regard to resistin, in the multivariate model, only the association between resistin and IL-6 was found (β = 0.33, p = 0.002). The association between resistin and IL-6 was confirmed in group 1 (β = 0.46, p = 0.004) but not in group 2.. Until today, the present study represents the first investigating difference in the adipokine pattern between PsA patients with psoriasis and sine psoriasis. We report a strict interplay between leptin, female gender, BMI, and inflammatory activity in overall PsA patients. In PsA patients with clinical evident psoriasis, leptin was associated with female gender and BMI, and a close association between resistin and IL-6 was found. Further, a positive association between leptin levels and BMI and CRP was found in PsA sine psoriasis patients. Further studies are also advocated for clarifying the possible role of these adipokines as laboratory findings or as disease mediators in addressing the different phenotypes of the disease. Key Points •Levels of TNF-α, IL-6, leptin, resistin, visfatin, and ghrelin did not differ between PsA patients with clinical evident psoriasis and PsA sine psoriasis. •There is a strict interplay between leptin, female gender, BMI, and inflammatory activity in PsA. •There is a close association between resistin and IL-6 in PsA patients with clinical evident psoriasis.

Topics: Adipokines; Adult; Arthritis, Psoriatic; Cross-Sectional Studies; Female; Ghrelin; Humans; Inflammation; Interleukin-6; Leptin; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Psoriasis; Resistin; Sex Factors; Tumor Necrosis Factor-alpha

Leptin is an adipocyte-derived cytokine secreted mostly by adipose tissue. Serum leptin levels are elevated in obese individuals and correlate positively with body mass index (BMI). Interestingly, serum leptin levels are also elevated in patients with psoriasis and correlate positively with disease severity. Psoriasis is associated with obesity; patients with psoriasis have a higher incidence of obesity, and obese individuals have a higher risk of developing psoriasis. Additionally, obese patients with psoriasis experience a more severe degree of psoriasis. In this study, we hypothesised that leptin may link psoriasis and obesity and plays an aggravating role in psoriasis. To investigate leptin's role in psoriasis, we applied the widely accepted imiquimod (IMQ)-induced psoriasis-like skin inflammation mouse model on leptin-deficient (ob/ob) mice and evaluated psoriasis severity. Moreover, we stimulated human keratinocytes with leptin and investigated the effect on proliferation and expression of pro-inflammatory proteins. In ob/ob mice, clinical signs of erythema, infiltration and scales in dorsal skin and inflammation in ear skin, as measured by ear thickness, were attenuated and compared with wt mice. Moreover, IL-17A and IL-22 mRNA expression levels, as well as increased epidermal thickness, were significantly less induced. In vitro, the effect of leptin stimulation on human keratinocytes demonstrated increased proliferation and induced secretion of several pro-inflammatory proteins; two hallmarks of psoriasis. In conclusion, leptin deficiency attenuated IMQ-induced psoriasis-like skin inflammation in a mouse model, and leptin stimulation induced a pro-inflammatory phenotype in human keratinocytes, thus, supporting an aggravating role of leptin in psoriasis.

Topics: Aminoquinolines; Animals; Cell Proliferation; Cells, Cultured; Chemokine CCL20; Chemokine CXCL1; Gene Expression; Humans; Imiquimod; Interleukin-17; Interleukin-22; Interleukin-6; Interleukins; Keratinocytes; Leptin; Male; Matrix Metalloproteinase 9; Mice; Mice, Knockout; Psoriasis; RNA, Messenger

Leptin, an adipocyte-derived circulating cytokine that signals nutritional status, may play a role in the development of psoriasis and its associated systemic diseases. Patients with psoriasis have significantly decreased serum leptin levels compared with controls.. To investigate the effect of two commonly used anti-psoriatic biologic drugs, adalimumab and ustekinumab, on leptin and leptin receptor expression in human macrophages.. THP-1 differentiated macrophages were cultured under the following conditions: (i) untreated control, (ii) adalimumab 5 μg/mL, (iii) ustekinumab 1 μg/mL and (iv) ustekinumab 5 μg/mL. Expression of leptin and leptin receptors were measured using real-time quantitative PCR and immunoblotting techniques.. The presence of either adalimumab or ustekinumab in growth medium significantly upregulated expression of leptin receptor in THP-1 human macrophages to 1.98 ± 0.47 and 2.09 ± 0.24, respectively (n = 3, P < 0.01) vs. 1.12 ± 0.19 for untreated control cells. However, only ustekinumab at a concentration of 5 μg/mL augmented expression of leptin to 1.99 ± 0.56 (n = 3, P < 0.01) vs. control untreated cells.. Enhanced leptin and leptin receptor expression in macrophages exposed to therapeutic levels of ustekinumab suggest a novel immunomodulatory mechanism for this biologic drug. Further mechanistic studies may yield targeted treatment using the leptin pathway, which could reduce the common obesity-related complications of psoriasis while alleviating symptoms and improving prognosis.

Topics: Adalimumab; Biomarkers; Blotting, Western; Dermatologic Agents; Humans; Interleukin-12; Interleukin-23; Interleukins; Leptin; Macrophages; Psoriasis; Receptors, Leptin; Ustekinumab

Topics: Case-Control Studies; Cells, Cultured; Cytokines; Enzyme-Linked Immunosorbent Assay; Fibroblasts; Humans; Leptin; Obesity; Psoriasis

The presented article studies the role of selected inflammatory and anti-inflammatory serum markers of psoriatic patients in the pathogenesis of metabolic syndrome (MS) and psoriasis. The study is based on the comparison between the group of psoriatic patients (74) and the control group (65). We found significantly higher BMI (

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Adiponectin; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Blood Pressure; Body Mass Index; C-Reactive Protein; Case-Control Studies; Female; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Psoriasis; Resistin; Waist Circumference; Young Adult

Recent studies have implicated adipokines in the pathogenesis of the immune-mediated inflammatory disease, psoriasis and its associated comorbidities. Hence, we undertook to study adipokine levels and indices of insulin resistance and sensitivity in patients with psoriasis vulgaris, in comparison with controls and their association with disease severity and response to therapy.. Sixty cases of psoriasis vulgaris and 60 age- and gender-matched healthy controls were included in this study. Severity grading according to psoriasis area severity index scoring was done in all psoriatics. Serum levels of adipokines [leptin, adiponectin, resistin and interleukin-6 (IL-6)] and insulin were estimated in all psoriatics at baseline and at 12 weeks on follow-up and in controls.. Baseline levels of the inflammatory adipokines (leptin, resistin and IL-6) and insulin resistance indices were significantly higher in psoriatics, as compared to controls, while that of the anti-inflammatory adipokine, adiponectin and insulin sensitivity indices were significantly lower in psoriatics, as compared with controls. Baseline inflammatory adipokines, serum insulin level and insulin resistance indices demonstrated a significant positive correlation with the severity of psoriasis, while the anti-inflammatory adipokine, adiponectin and insulin sensitivity indices demonstrated a significant negative correlation with the disease severity. After 12 weeks of therapy (both topical and systemic), there was a significant reduction in the levels of inflammatory adipokines and a significant increase in the levels of anti-inflammatory adipokine-adiponectin. However, a significant decrease in insulin levels and insulin resistance indices were observed only with systemic therapy with methotrexate.. The present results implicate that adipokines are significantly associated with pathogenesis of psoriasis and hence adequate and early control of psoriasis may contribute to the decreased development of metabolic syndrome, including the risk of cardiovascular disease.

Topics: Adiponectin; Adolescent; Adult; Aged; Case-Control Studies; Coal Tar; Female; Humans; Immunosuppressive Agents; Insulin Resistance; Interleukin-6; Keratolytic Agents; Leptin; Male; Methotrexate; Middle Aged; Prospective Studies; Psoriasis; Resistin; Severity of Illness Index; Young Adult

Psoriasis has been considered as a systemic disease associated with obesity, cardiovascular diseases and metabolic syndrome. Adipokines have influence on many metabolic processes. Aim of this study was to evaluate the effect of conventional topical treatment on serum adiponectin and leptin levels in patients with psoriasis.. Forty-nine patients with relapse of plaque-type psoriasis and 16 healthy controls were examined. Blood samples were collected before therapy and after 14 days of application. Serum adiponectin and leptin concentrations were examined by enzyme-linked immunosorbent assay for correlations with effectiveness of topical treatment.. Adiponectin and leptin serum levels were significantly decreased in psoriatic patients in comparison to the controls. As a result of the topical treatment, serum adiponectin level did not significantly change. Serum leptin level increased significantly, still remaining lower than in the controls.. Leptin might be a useful marker in assessing the efficacy of the treatment for psoriasis.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Biomarkers; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Male; Middle Aged; Psoriasis; Young Adult

Altered secretion patterns of proinflammatory adipokines may influence the increased risk of cardiovascular mortality observed in patients with chronic inflammatory diseases.. To determine whether two adipokines, leptin and resistin, correlate with metabolic syndrome features and disease severity in psoriatic patients who underwent anti-TNF-α therapy.. Prospective study of consecutive non-diabetic patients with moderate-to-severe psoriasis who completed 6 months of therapy with anti-TNF-α- adalimumab. Patients with kidney disease, hypertension or body mass index ≥35 Kg/m(2) were excluded. Metabolic and clinical evaluation was performed at the onset of anti-TNF-α treatment and at month 6.. Twenty-nine patients were assessed. A correlation between adiposity and leptin was observed (waist circumference and leptin levels after 6 months of therapy: r = 0.43; P = 0.030). Leptin concentration also correlated with blood pressure before adalimumab onset (systolic: r = 0.48; P = 0.013 and diastolic blood pressure: r = 0.50; P = 0.010 ). A marginally significant negative correlation between insulin sensitivity (QUICKI) and leptin levels was also observed. CRP levels correlated with leptin prior to the onset of adalimumab (r = 0.45; P = 0.020) and with resistin both before (r = 0.45; P = 0.020) and after 6 months of therapy (r = 0.55; P = 0.004). A positive association between parameters of disease activity such as BSA (r = 0.60; P = 0.001) and PASI (r = 0.63; P = 0.001) prior to the onset of adalimumab therapy and resistin concentrations was also disclosed. No significant changes in leptin and resistin concentrations following the 6-month treatment with adalimumab were seen.. In patients with moderate-to-severe psoriasis leptin correlates with metabolic syndrome features and inflammation whereas resistin correlate with inflammation and disease severity.

Topics: Adalimumab; Adiposity; Adult; Anti-Inflammatory Agents; Blood Pressure; Body Surface Area; C-Reactive Protein; Female; Humans; Inflammation; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Prospective Studies; Psoriasis; Resistin; Severity of Illness Index; Sex Factors; Tumor Necrosis Factor-alpha; Waist Circumference

Adipocytokines are bioactive molecules that are deeply involved in the occurrence of atherosclerosis, obesity, and autoimmune inflammatory diseases.. This study was conducted to evaluate the effects of tumor necrosis factor-α (TNF-α) inhibitors on serum levels of adipocytokines in patients with chronic plaque psoriasis.. Serum levels of adiponectin, resistin, visfatin, leptin, TNF-α, and interleukin-6 (IL-6) were evaluated in sera obtained from 47 patients with psoriasis, both at baseline and after they had received TNF-α inhibitors for 24 weeks. Equivalent data were obtained for 39 control subjects matched by age, sex, body mass index, waist : hip ratio, geographical origin, Mediterranean dietary habits, and smoking habits.. At baseline, mean serum levels of TNF-α, IL-6, leptin, resistin, and visfatin were higher in the psoriasis group than in healthy controls; these differences were statistically significant (P < 0.05). Conversely, mean serum levels of adiponectin were significantly lower in patients with psoriasis than in controls (P < 0.0001). Serum levels of adipocytokines did not linearly correlate with anthropometric indices in psoriasis patients (P > 0.05), except in the case of leptin, for which serum levels were related to waist : hip ratio in both men and women (P < 0.05). After 24 weeks of treatment, although serum levels of proinflammatory adipocytokines were decreased, only that of leptin showed a statistically significant reduction (P = 0.0003). Serum levels of adiponectin, an anti-inflammatory adipocytokine, were only mildly increased and persisted at a significantly lower level than in healthy controls (P > 0.005).. Patients with psoriasis show an imbalance between pro- and anti-inflammatory adipocytokines, which is reduced but not normalized after administration of TNF-α inhibitors for 24 weeks. This partial rebalancing seems to be mainly related to a reduction in proinflammatory adipocytokines, rather than an increase in anti-inflammatory adipocytokines.

Topics: Adalimumab; Adipokines; Adiponectin; Adult; Anti-Inflammatory Agents, Non-Steroidal; Body Mass Index; Body Weight; Case-Control Studies; Etanercept; Female; Humans; Interleukin-6; Leptin; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Psoriasis; Resistin; Retrospective Studies; Severity of Illness Index; Tumor Necrosis Factor-alpha; Waist-Hip Ratio

Numerous reports have shown that psoriasis is associated with obesity and leptin. However, few reports are available on the association between serum leptin levels and leptin gene expression in SAT of psoriasis patients. To clarify this point, we examined serum leptin levels and expression levels of leptin messenger RNA (mRNA) in subcutaneous adipose tissue (SAT) of psoriasis patients. 17 psoriasis vulgaris patients and 6 non-obese control patients who underwent skin surgery were enrolled in this study. We measured serum leptin levels. SAT samples in psoriasis patients were taken from beneath the lesional psoriatic skin at the time of skin biopsy. Leptin mRNA expression in SAT was measured using quantitative real-time reverse transcription polymerase chain reaction (real-time RT-PCR) amplification. Leptin mRNA expression showed a positive correlation with serum leptin levels and BMI. We classified psoriasis patients into two groups according to BMI: the group of non-obese psoriasis patients (BMI < 25, n = 7), and the group of obese psoriasis patients (BMI ≥ 25, n = 10). PASI score, serum leptin levels and Leptin mRNA expression in SAT were significantly higher in the obese psoriasis patients than in the non-obese psoriasis patients. Leptin mRNA expression in SAT was correlated with circulating levels of leptin, the severity of psoriasis, and obesity in psoriasis patients. Serum leptin levels and leptin mRNA expression levels in SAT of non-obese psoriasis patients were not significantly different from those of non-obese controls. The altered secretion of leptin by SAT may be related to the severity of psoriasis.

Topics: Adipose Tissue; Aged; Aged, 80 and over; Body Mass Index; Female; Gene Expression Regulation; Humans; Leptin; Male; Middle Aged; Obesity; Psoriasis; Real-Time Polymerase Chain Reaction; RNA, Messenger

Identifying psoriasis patients who present a higher risk of developing cardiovascular co-morbidities is of upmost importance. Two key adipokines, leptin and adiponectin, may play a role connecting psoriasis and its major co-morbidities.. To evaluate the potential contribution of LEPrs2167270(19 G/A), LEPRrs1137100(326 A/G) and ADIPOQrs1501299(276 G/T) gene polymorphisms in psoriasis susceptibility and their influence in epicardial adipose tissue and abdominal visceral fat volume and subclinical atherosclerosis in severe psoriasis patients.. One hundred severe psoriasis patients underwent clinical and laboratory evaluation, DNA genotyping and multi-detector computed tomography scan for epicardial adipose tissue, abdominal visceral fat and coronary artery calcification assessment. DNA control group was obtained from a previously anonymized biobank of 206 adult subjects without psoriasis.. No association was observed between the studied gene polymorphisms and psoriasis susceptibility, CAC or increased EAT or AVF volume.. The studied polymorphisms do not seem, at least in this cohort of patients, to be a genetic risk factor for the development of atherosclerosis or increased adiposity in psoriasis.

Topics: Adiponectin; Adult; Aged; Atherosclerosis; Calcinosis; Cohort Studies; Coronary Vessels; Female; Gene Expression; Genotype; Humans; Intra-Abdominal Fat; Leptin; Male; Middle Aged; Obesity; Pericardium; Polymorphism, Single Nucleotide; Psoriasis; Receptors, Leptin; Severity of Illness Index

Psoriasis is associated with metabolic activity of adipose tissue which produces pro- and anti-inflammatory adipokines. Goeckerman therapy (GT) represents an effective treatment of psoriasis. This study evaluated variation of selected inflammatory and metabolic markers during GT and the relationships between the markers, severity of the disease (PASI score), body mass, and the basic characteristics of the therapy. The study was conducted on a group of patients (n = 32) and on a control group (n = 24). Before GT, we found significantly elevated levels of proinflammatory CRP (p < 0.001) and leptin (p < 0.05) in psoriatic patients (compared to the controls). The therapy significantly decreased the levels of CRP and adiponectin. We found positive correlations between CRP and total duration of GT (p < 0.05) and CRP and the time of UV exposure (p < 0.01) and negative correlations between adiponectin and the total duration of GT (p < 0.05) and adiponectin and the application of CCT ointment (p < 0.001). From our results, we can conclude that GT causes partial reduction of both proinflammatory and anti-inflammatory markers. However, the levels of proinflammatory CRP and leptin remained significantly higher in the patients than in the control group.

Topics: Adiponectin; Adult; Aged; Biomarkers; Body Mass Index; C-Reactive Protein; Female; Humans; Leptin; Male; Middle Aged; Ointments; Psoriasis; Severity of Illness Index

Psoriasis is an inflammatory skin disease that may be associated with an adverse cardiometabolic profile including modulated plasma adiponectin and leptin levels. Whether these levels are independent of cardiometabolic risk factors, which are also prevalent in psoriasis, is not known.. A consecutive sample of 122 participants with varying degrees of psoriasis severity, and a random sample of 134 participants without psoriasis, were recruited for this case-control study. Cardiometabolic risk factors including traditional cardiovascular risk factors, waist circumference, insulin resistance, and total plasma adiponectin and leptin were measured. Total plasma adiponectin and leptin levels were compared in unadjusted and adjusted analyses by psoriasis status.. Participants with psoriasis had mostly mild disease and were mainly on topical therapies, but still had a more adverse cardiometabolic profile compared with those without psoriasis. Furthermore, plasma adiponectin levels were significantly lower in participants with psoriasis than those without {7.13 μg/mL [interquartile range (IQR) 4.9-11.3) vs. 14.5 μg/mL (IQR 8.4-24.1); P < 0.001]}. Plasma leptin (ng/mL) levels were higher in the psoriasis group but this did not reach statistical significance [11.3 (IQR 6.4-21.8) vs. 9.8 (IQR 4.9-20.5); P = 0.07]. In multivariable modelling, plasma adiponectin levels were still negatively associated with psoriasis status after adjusting for waist size (% difference = -41.2%, P < 0.001), insulin resistance (% difference = -39.5%, P < 0.001), and both waist size and insulin resistance (% difference = -38.5%, P < 0.001).. Plasma levels of adiponectin were lower in psoriasis, and this relationship persisted after adjusting for cardiometabolic risk factors known to decrease adiponectin levels. These findings suggest that inflammation present in psoriasis may be associated with adipose tissue dysfunction; however, direct studies of adipose tissue are needed to confirm this.

Topics: Adiponectin; Adult; Cardiovascular Diseases; Case-Control Studies; Female; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Multivariate Analysis; Psoriasis; Risk Factors; Waist Circumference

Psoriasis is a disorder caused by genetic and immunological factors. Leptin, a peptide hormone secreted predominantly from adipose tissue, regulates energy intake and expenditure, as well as the T-helper response. There have been conflicting reports regarding serum levels of leptin and adiponectin in patients with psoriasis. In the present study, we measured serum levels of leptin and adiponectin in Korean patients with psoriasis. Twenty-four patients with psoriasis and fifteen control subjects were included in the study. Serum leptin and adiponectin levels were determined by an immunometric sandwich enzyme-linked immunosorbent assay (ELISA). The mean serum leptin concentration in patients with psoriasis was higher than in controls, and the difference was statistically significant. In contrast, serum adiponectin levels in patients with psoriasis were significantly decreased compared with healthy controls. Leptin levels in vitamin D-deficient patients were statistically significantly higher than in vitamin D-sufficient patients. Serum adiponectin concentrations showed a negative correlation with body mass index (BMI) and psoriasis area and severity index (PASI) in patients with psoriasis. In conclusion, the present study demonstrated that leptin and adiponectin may play a role in the immunopathogenesis of psoriasis and may be useful biomarkers indicating severity of psoriasis in Korean patients.

Topics: Adiponectin; Adult; Aged; Biomarkers; Body Mass Index; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammation; Leptin; Male; Middle Aged; Psoriasis; Republic of Korea; Risk; Severity of Illness Index; Vitamin D; Vitamin D Deficiency; Young Adult

Psoriasis patients are often susceptible to cardiovascular diseases (CVD), including atherosclerosis. Traditional markers (biochemical and inflammatory) and diagnostic tools could detect occlusive but not subclinical atherosclerosis. Carotid intima-media thickness (CIMT), has recently been recognised as a non invasive diagnostic tool for identification of premature atherosclerosis. Therefore we evaluated 80 psoriasis patients and 80 age sex matched healthy controls for serum leptin levels and apolipoprotein B/apolipoprotein A-I ratio (apoB/apoA-I ratio) in relation with CIMT of carotid artery. Carotid intima-media thickness and carotid plaques were simultaneously measured by carotid sonography. Serum concentration of leptin and apolipoprotein were measured using enzyme-linked immuno sorbent assay (ELISA) and nephelometry respectively. Raised CIMT correlated to age of onset of the disease, serum leptin and apoB/apoA-I ratio in psoriasis patients. Taking into account, values that were above the 75 percentile of the three markers (leptin, apoB/apoA-I ratio and CIMT) the odds ratio was 4.26 (2.06-8.80 CI). Leptin and apoB/apoA-I ratio showed significant cumulative association with CIMT. Results of predictive analysis supports measurement of CIMT along with estimation of serum leptin and apoB/apoA-I ratio for prediction of premature atherosclerosis in psoriasis patients.

Topics: Adult; Apolipoprotein A-I; Apolipoproteins B; Atherosclerosis; Carotid Intima-Media Thickness; Case-Control Studies; Female; Humans; Leptin; Male; Middle Aged; Predictive Value of Tests; Psoriasis

Patients with psoriasis may have an increased risk of cardiovascular disease.. We sought to evaluate the potential association between subclinical atherosclerosis and psoriasis by measuring the intima-media wall thickness (IMT) of the common carotid artery (CCA) in patients with psoriasis and evaluating its correlation with serum leptin and resistin levels.. The mean IMT (MIMT) of the CCA and leptin, resistin, triglyceride (TG), and total cholesterol levels in serum were determined in 60 patients and 60 healthy sex- and age-matched control subjects.. Compared with the healthy control subjects, patients with psoriasis had significantly higher MIMT of the CCA and higher levels of serum leptin, resistin, TG, and total cholesterol. In addition, MIMT of the CCA was positively correlated with serum leptin, resistin, TG, and total cholesterol levels in patients with psoriasis.. This was a cross-sectional single-center study, and we could not evaluate additional biomarkers such as adipokine or adiponectin because of our restricted facilities.. Although serum leptin, resistin, TG, and total cholesterol levels and MIMT of the CCA were significantly increased in patients with psoriasis, MIMT of the CCA was also positively correlated with these biomarkers. Therefore, psoriasis could be an independent risk factor for subclinical atherosclerosis.

Topics: Adolescent; Adult; Age Distribution; Aged; Aged, 80 and over; Atherosclerosis; Biomarkers; Carotid Intima-Media Thickness; Carotid Stenosis; Case-Control Studies; Comorbidity; Female; Humans; Incidence; Leptin; Male; Middle Aged; Prognosis; Psoriasis; Resistin; Risk Assessment; Severity of Illness Index; Sex Distribution; Statistics, Nonparametric; Young Adult

Topics: Female; Humans; Leptin; Male; Psoriasis

Investigations about prevalence of obesity in psoriasis patients are increased nowadays. Higher serum levels of leptin in patients with psoriasis who are overweight or obese suggest that leptin may serve as a molecular link between psoriasis and metabolic comorbidities. However, the pathological functions of leptin in psoriasis are not clearly understood. We investigated the influence of being overweight or obese on the risk of psoriasis, and the relationship between serum leptin levels and the severity of psoriasis in Chinese Han patients. We also investigated biological effects of leptin on the proliferation and secretion of pro-inflammatory cytokines by human keratinocytes in vitro. Obesity was a significant risk factor for psoriasis in the Chinese Han population; however, we did not observe a significant correlation between Psoriasis Area and Severity Index (PASI) and body mass index (BMI). We observed a positive correlation between the serum leptin level and PASI in overweight and obese male patients with psoriasis. Strong leptin immunoreactivity was detected in the epidermis of psoriatic lesions, particularly in keratinocytes. Leptin significantly increased the proliferation and secretion of pro-inflammatory cytokines by keratinocytes in vitro. In conclusion, this study suggests leptin as a novel molecular link between psoriasis and obesity, which may help to explain the more server conditions of psoriasis in patients with obesity.

Topics: Adolescent; Adult; Aged; Body Mass Index; Cell Cycle; Cell Proliferation; Cells, Cultured; China; Cytokines; Female; Gene Expression Regulation; Humans; Inflammation; Keratinocytes; Leptin; Male; Middle Aged; Obesity; Overweight; Psoriasis; Young Adult

Psoriasis has been related to metabolic syndrome (MS). Adipocytokines produced by white adipose tissue may be involved in the pathogenesis of psoriasis and its association with MS. Our objectives were to characterize the profile of a number of different inflammatory and atherogenic markers, vitamins, adipokines and cytokines and their potential involvement in MS in patients with moderate-to-severe psoriasis without joint involvement compared to anthropometrically matched controls, and to evaluate correlation with severity of the skin disease and changes after narrow-band UVB (NB-UVB) phototherapy. We designed a prospective cross-sectional study. Baseline waist circumference, body fat composition, lipid, carbohydrate and calcium metabolism profile, inflammation markers, homocysteine and vitamins D, B6, B12 and folic acid, leptin, resistin, omentin, lipocalin-2, adipocyte fatty acid-binding protein, retinol-binding protein-4 (RBP-4), interleukin-6, soluble tumour necrosis factor receptor 1 (sTNFR1) and interleukin-17 of 50 psoriasis patients and 50 gender, age and body mass index-matched controls were recorded, then evaluated after NB-UVB in the patients. The patients had higher baseline serum concentrations of leptin, RBP-4, lipocalin-2 and sTNFR1. Baseline psoriasis area and severity index correlated with serum concentrations of RBP-4 and lipocalin-2 only. Principal components analysis disclosed a component including vitamins B12, B6, folic acid, calcidiol and HDL-cholesterol that was only present in healthy controls and opposed to a cluster of variables which promote MS. This component was absent in the patients. Our results point to lipocalin-2 and RBP-4 as relevant mediators of the trend towards MS in psoriatic patients.

Topics: Acute-Phase Proteins; Adult; Biomarkers; Child; Child, Preschool; Cross-Sectional Studies; Disease Progression; Female; Humans; Infant; Leptin; Lipocalin-2; Lipocalins; Male; Metabolic Syndrome; Middle Aged; Prospective Studies; Proto-Oncogene Proteins; Psoriasis; Receptors, Tumor Necrosis Factor, Type I; Retinol-Binding Proteins, Plasma; Severity of Illness Index; Ultraviolet Therapy; Vitamin B 12; Young Adult

To compare the prevalence of metabolic syndrome (MetS) and the levels of related biomarkers in patients with psoriatic arthritis (PsA) and psoriasis without arthritis (PsC).. This study compared patients with PsA and patients with PsC. The presence of MetS was determined. Serum levels of insulin, adiponectin and leptin were measured. The homeostasis model assessment for insulin resistance (HOMA-IR) was calculated. HOMA-IR, adiponectin and leptin were log-transformed. Continuous variables were compared using the t test and the χ(2) test was used for discrete variables. Multivariate regression models were used to investigate the association of MetS and adiponectin with PsA compared to PsC after adjusting for potential confounding variables.. 203 PsA and 155 PsC patients were analysed. The prevalence of MetS was higher in PsA patients compared to those with PsC. However, this did not reach statistical significance (36.5% vs 27.1%, p=0.056). The levels of adipokines were significantly higher in PsA compared to PsC: adiponectin (8.8±5.2 vs 7.4±4.5 log (µg/ml), p=0.009) and leptin in women (3.1±0.8 vs 2.8±0.8, log (ng/ml), p=0.04). HOMA-IR was also higher in PsA (0.97±0.63 vs 0.68±0.81, p<0.001). No difference was observed in leptin levels in men. In multivariate regression analysis, PsA (p=0.04) and the psoriasis area and severity index score (p=0.02) were associated with MetS. Adiponectin was significantly associated with PsA (p=0.005), the use of anti-tumour necrosis factor α therapy (p=0.03) and active joint count (p=0.001).. MetS and related adipokines correlated with an increased burden of skin and joint inflammation.

Topics: Adipokines; Adult; Antirheumatic Agents; Arthritis, Psoriatic; Biomarkers; Cross-Sectional Studies; Female; Humans; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Psoriasis; Risk Factors; Severity of Illness Index

Leptin, an adipocyte-derived hormone, has been shown to have several immunological effects similar to those of proinflammatory cytokines. The relationship between serum leptin, psoriasis, and obesity is still conflicted, and very few studies have investigated its role in skin diseases other than psoriasis.. To evaluate the possible relationship between serum leptin in nonobese patients with psoriasis and other randomly selected skin diseases.. Eighty subjects (40 patients with psoriasis, 20 patients with other randomly selected skin diseases, and 20 healthy controls) were included in the study. Fasting serum leptin levels of the study groups were examined by sandwich enzyme-linked immunosorbent assay.. Elevated serum leptin levels were detected in both nonobese patients with psoriasis (P=.004) and those with other randomly selected skin diseases (P=.05). Leptin levels failed to correlate to the Psoriasis Area and Severity Index score of psoriatic patients. Both sexes demonstrated comparable levels of serum leptin in psoriatic patients, while female patients suffering from other skin diseases showed higher levels of serum leptin than did males of the same group.. Leptin may play a role in the immunopathogenesis of psoriasis and other skin diseases, even in the absence of obesity as a cofactor.

Topics: Adult; Aged; Body Mass Index; Body Weight; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Male; Middle Aged; Obesity; Psoriasis; Severity of Illness Index; Skin; Skin Diseases; Young Adult

Psoriasis, a chronic inflammatory immune disorder, has been linked to increased cardiovascular mortality and morbidity. Leptin, an obesity-related peptide, has been shown to exert direct effects on the vascular endothelium and on vascular smooth muscle cells. Carotid intima-media thickness (IMT) measurement is a promising tool for detecting atherosclerosis in its pre-occlusive/subclinical phase.. The objective of the study was to evaluate carotid IMT and serum leptin levels in psoriatic patients as an indicator of subclinical atherosclerosis.. The study was conducted in 50 psoriatic patients and 10 healthy controls. The clinical severity of skin affection in psoriatic patients was estimated using the psoriatic area and severity index (PASI). Serum leptin levels (ng\\ml) and lipid profiles [including serum triglyceride (TG), serum low density lipoproteins (LDL) and serum high density lipoproteins (HDL)] were measured from blood samples. Carotid IMT was measured using carotid duplex ultrasonography.. Psoriatic patients showed significantly higher leptin levels and higher IMT than controls. The mean of the intima-media thickness of the four vessels examined (MIMT) showed a positive correlation with patients' mean ages, disease duration, body mass index, PASI scores, systolic blood pressure, diastolic blood pressure, leptin levels, LDL levels and triglyceride levels and no correlation with the mean HDL level.. Psoriasis is an independent risk factor for subclinical atherosclerosis. This cardiovascular impairment is influenced mainly by disease severity, serum TG levels and serum leptin levels.

Topics: Adult; Biomarkers; Carotid Intima-Media Thickness; Female; Humans; Leptin; Male; Middle Aged; Psoriasis; Reproducibility of Results; Sensitivity and Specificity; Ultrasonography

White adipose tissue is known to be involved in numerous physiological processes such as insulin-mediated functions, lipid and glucose metabolism, vascular changes and coagulation. These processes are mainly mediated by adipokines that are secreted either from adipocytes or cells of the stromal-vascular fraction of adipose tissue. In obesity, a shift in the production of adipokines can mediate the development of associated diseases, such as metabolic syndrome, and vascular complications, such as artherosclerosis, myocardial infarction or stroke, which are known comorbidities of psoriasis too. As obesity is a frequently seen comorbidity in psoriasis patients, adipokines could be involved in the pathogenesis of psoriasis and/or its comorbidities either dependently or independently from obesity. Therefore, this study investigates the levels of four major adipokines in psoriasis patients compared with a control group of healthy volunteers without chronic inflammatory diseases in relation to body composition. Leptin, adiponectin (high molecular weight (HMW) and total adiponectin), visfatin and retinol-binding protein 4 (RBP4) have been analysed in 79 psoriasis patients and in 80 healthy volunteers. It was shown that HMW adiponectin (OR 1.3755; P = 0.0094) and visfatin (OR 1.1267; P = 0.0472) are independently increased, and RBP4 (OR 0.9884; P < 0.0001) is independently decreased in psoriasis. In conclusion, increased levels of HMW adiponectin and decreased levels of RBP4 could be a mechanism in a chronic inflammatory state that helps to protect against vascular and metabolic disorders, whereas the increase of the pro-inflammatory adipokine visfatin could lead to atherosclerosis and vascular disorders found in psoriasis.

Topics: Adiponectin; Body Mass Index; Case-Control Studies; Female; Humans; Leptin; Logistic Models; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Nutritional Status; Psoriasis; Retinol-Binding Proteins, Plasma; Waist-Hip Ratio

Cyclosporin has various effects on adipose tissue and glucose metabolism. This situation may lead to changes in serum levels of adipocyte-derived cytokines which have influence on the pathogenesis of psoriasis. The aim of this study was to evaluate the effect of cyclosporin treatment on some adipocyte-derived cytokines in psoriatic patients. This case-control study was performed between June 2009 and March 2010, at the Department of Dermatology of Meram School of Medicine. Serum leptin, adiponectin, resistin and ghrelin levels were assessed in 26 patients with psoriasis before and after cyclosporin treatment and body mass index-matched 26 healthy control subjects. The adipokines levels were compared between the groups. Serum leptin, ghrelin, resistin and adiponectin levels in patients with psoriasis before the treatment were higher than those of the control group but the differences were not statistically significant. A positive correlation between serum leptin and family history of psoriasis was detected (r = 0.398, P = 0.044). A strong negative correlation between the Psoriasis Area and Severity Index and serum ghrelin levels was seen (r = -0.52, P = 0.001) and there was a strong positive correlation between the Nail Psoriasis Severity Index and serum resistin levels (r = 0.62, P = 0.001). Following the treatment, a significant increase was seen in the serum level of adiponectin (P = 0.02) and resistin (P = 0.003). The correlations between the adipokines and the disease parameters before the treatment were lost after the treatment. Our results suggest that levels of some adipocyte-derived cytokines in psoriatic patients are affected by cyclosporin treatment.

Topics: Adipokines; Adiponectin; Adult; Case-Control Studies; Cyclosporine; Female; Ghrelin; Humans; Immunosuppressive Agents; Leptin; Male; Middle Aged; Psoriasis; Resistin

A link between psoriasis and risk for cardiovascular disease (CVD) is supposed. Adipokines (adiponectin and leptin) playing roles in inflammation as well as lipid metabolism could have impact on CVD.. We investigated links between adiponectin and leptin levels and several inflammation- and oxidative stress-related CVD risk makers in patients with psoriasis.. Sixty patients with plaque-type psoriasis with normal total cholesterol levels belonging to three body mass index (BMI) categories: BMI < 24.9, BMI 25.0-29.9 and BMI ≥ 30.0 kg/m(2) were studied. Fasting blood samples were analysed for adiponectin, leptin, high-sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), oxidized low density lipoprotein (oxLDL), oxidized LDL/β(2) -glycoprotein complexes (oxLDL-β(2)-GPI) and standard blood lipid panel.. In patients, adiponectin was negatively (P < 0.005), and leptin, oxLDL and oxLDL-β(2) -GPI levels were positively correlated to BMI (P < 0.005, P < 0.05, and P < 0.01, respectively). Patients had higher hsCRP and IL-6 levels as compared with the endemic reference values. High adiponectin was strongly associated with higher TNF-α and high density lipoprotein cholesterol (P = 0.001), and lower triglycerides (TG) (P = 0.01) as well as oxLDL-β(2) -GPI levels (P < 0.05). After multivariate adjustment, the association for TNF-α and TG remained significant (P < 0.01 for both). Multiple regression analysis also revealed that leptin concentration was significantly associated with hsCRP, oxLDL and TG levels.. The data suggest that in addition to the strong effect of inflammation and LDL oxidation, adipokine level may be one of the mechanisms behind the close association between psoriasis and CVD. Given the significant relations of several markers with BMI, health consequences of excessive weight should be better communicated to patients with psoriasis.

Topics: Adiponectin; Adult; Biomarkers; Body Mass Index; Cardiovascular Diseases; Female; Humans; Leptin; Male; Psoriasis

Psoriasis is a disorder with genetic and immunologic background. Leptin can regulate the T-helper response.. Our primary goal is to study the functional polymorphism (G-2548A) of the leptin (LEP) gene in the genetic predisposition of psoriasis, and our secondary goal is to examine factors affecting plasma leptin levels in psoriasis and to compare patients with and without metabolic syndrome (MS).. The study involved 94 patients with psoriasis and 100 healthy controls. Analysis of G-2548A polymorphism of the LEP gene was made by the PCR and restriction fragment length polymorphism technique. The relationship between LEP gene polymorphism and the clinical features of the patients was analysed. Plasma leptin levels and proportions of comorbidities in patients vs controls were compared.. In controls, the GA, AA and GG frequencies were 50%, 30% and 20%, respectively, while in patients, the distribution of genotypes was 42.5%, 20.2% and 38.3%, respectively, with significant difference (P = 0.014) between patients and controls. In patients with MS, the GG, GA and AA frequencies were 61.5%, 23.1% and 15.4%, respectively, while in patients without MS, the distribution of genotypes was 29.4%, 50% and 20.6%, respectively, with significant difference (P = 0.014) between both groups. Plasma leptin showed a significant higher levels in the patients versus the controls (P < 0.001), and among the different LEP genotypes (P < 0.001) in the patients' group.. LEP G-2548A polymorphism could be a predictor for higher plasma leptin and increased risk of psoriasis and could be used as a marker for psoriasis-related comorbidity risk.

Topics: Base Sequence; Biomarkers; Case-Control Studies; DNA Primers; Female; Gene Frequency; Genetic Markers; Genetic Predisposition to Disease; Humans; Leptin; Male; Metabolic Syndrome; Polymorphism, Single Nucleotide; Psoriasis; Risk Factors

Topics: Adult; Chemokines; Chronic Disease; Cyclosporine; Dermatitis; Female; Humans; Hypercholesterolemia; Hypertriglyceridemia; Intercellular Signaling Peptides and Proteins; Leptin; Male; Metabolic Syndrome; Psoriasis; Skin; Up-Regulation

Topics: Adiponectin; Adult; Aged; Body Mass Index; Female; Humans; Japan; Leptin; Male; Middle Aged; Obesity; Prevalence; Psoriasis; Tumor Necrosis Factor-alpha

Topics: Adiponectin; Adult; Aged; Body Mass Index; Female; Humans; Japan; Leptin; Male; Middle Aged; Obesity; Prevalence; Psoriasis; Tumor Necrosis Factor-alpha

Obesity is a significant risk factor for psoriasis and body mass index (BMI) correlates with disease severity. Objectives To investigate the relationship between obesity and psoriasis, focusing on the role of adipokines such as leptin and resistin.. Patients with psoriasis (n = 30) were recruited and their BMI, waist circumference and disease severity [Psoriasis Area and Severity Index (PASI)] were recorded. Fasting serum samples were obtained on enrolment and after a course of ultraviolet (UV) B treatment. Age-, sex- and BMI-matched healthy controls were also recruited.. On enrolment, serum leptin and soluble leptin receptor levels were not raised compared with the controls. However, resistin, interleukin (IL)-1beta, IL-6, and chemokines CCL2, CXCL8 and CXCL9 were all significantly elevated in the patient group and serum resistin correlated with disease severity (r = 0.372, P = 0.043). Improvement after UVB treatment was accompanied by decreased serum CXCL8. In vitro, both leptin and resistin could induce CXCL8 and tumour necrosis factor-alpha production by blood monocytes, and leptin could additionally induce IL-1beta and IL-1 receptor antagonist production. Leptin also dose dependently increased secretion of the growth factor amphiregulin by ex vivo-cultured lesional psoriasis skin.. These data support the view that leptin and resistin may be involved in the pathogenesis of psoriasis in overweight individuals, possibly by augmenting the cytokine expression by the inflammatory infiltrate.

Topics: Adipokines; Adult; Aged; Aged, 80 and over; Amphiregulin; Body Constitution; Body Mass Index; Chronic Disease; Cytokines; Down-Regulation; EGF Family of Proteins; Female; Glycoproteins; Humans; Inflammation Mediators; Intercellular Signaling Peptides and Proteins; Leptin; Male; Middle Aged; Obesity; Psoriasis; Receptors, Leptin; Resistin; Reverse Transcriptase Polymerase Chain Reaction; Severity of Illness Index; Skin; Tissue Culture Techniques; Ultraviolet Therapy

Recent studies support the relation of psoriasis with obesity and cardiovascular disease. Leptin, a peptide hormone secreted predominantly from adipose tissue, is involved in the regulation of energy intake and expenditure. Recently, it has been shown to have several immunological effects including induction of proinflammatory cytokine production.. To investigate the possible role of leptin in psoriasis pathogenesis.. Forty-three patients with psoriasis, 10 diseased and 10 healthy controls with normal body mass index were included. Serum fasting leptin levels of the study group were examined by enzyme-linked immunosorbent assay. Tissue leptin and leptin receptor expression of both patients and controls were investigated by immunohistochemistry.. Serum leptin levels, tissue leptin and leptin receptor expression were significantly higher in patients with severe psoriasis than patients with mild-moderate psoriasis and controls (P < 0.05). Serum leptin levels showed a positive correlation with Psoriasis Area and Severity Index and involved body surface area in patients with psoriasis. In addition, serum leptin levels, tissue leptin and leptin receptor expression showed a positive correlation with disease duration in patients with psoriasis (P < 0.01, r = 0.979; P < 0.01, r = 0.691; P < 0.01, r = 0.428, respectively).. We assume that leptin might serve as a marker of severity in psoriasis and also may be a pathogenetic cofactor contributing to chronicity of the disease. Consequently, its role in obesity and cardiovascular disease in patients with psoriasis deserves to be studied. In addition, drugs targeting the proinflammatory effects of leptin may be a new adjuvant therapeutic approach in psoriasis.

Topics: Adult; Biomarkers; Body Composition; Body Mass Index; Epidemiologic Methods; Female; Humans; Leptin; Male; Middle Aged; Psoriasis; Receptors, Leptin

Topics: Adiponectin; Adult; Aged; Asian People; Female; Humans; Leptin; Male; Middle Aged; Psoriasis; Tumor Necrosis Factor-alpha

To evaluate the role of leptin, a 16-kDa adipocyte-derived hormone, in the development of metabolic dysregulation of psoriasis.. Case-control study.. Referral centers. Patients Seventy-seven patients with psoriasis and 81 age- and sex-matched control subjects were included in the study. Intervention Enzyme-linked immunoassay of serum samples from study subjects.. Serum leptin levels and proportions of comorbidities (including hypertension, diabetes mellitus, metabolic syndrome, hypertriglyceridemia, and reduced high-density lipoprotein cholesterol concentrations) in cases vs controls were compared using chi(2) and Mann-Whitney tests. The clinical significance of leptin in psoriasis was analyzed using logistic regression models.. Significantly more obesity (odds ratio [OR], 2.67) and hypertension (2.17) (P =.04 for both) were observed in subjects with psoriasis. High serum leptin levels (>or=7397.43 pg/mL) were found in female subjects (OR, 6.05; P < .001) and in subjects with obesity (3.45; P =.01), hypertension (2.19; P =.04), metabolic syndrome (3.58; P =.008), and psoriasis (2.25; P =.02). On multivariate analysis, psoriasis (OR, 4.57; P =.009) was significantly associated with hyperleptinemia independent of female sex (26.36; P < .001), metabolic syndrome (4.37; P =.04), and obesity (2.83; P =.12). Finally, patients with psoriasis who had hyperleptinemia tended to be female (P < .001) and manifested obesity (P =.002) and metabolic syndrome (P =.003).. Hyperleptinemia is associated with psoriasis independent of female sex and other conventional cardiovascular risk factors such as obesity and metabolic syndrome. Hyperleptinemia in psoriasis may contribute to metabolic syndrome.

Topics: Adult; Aged; Case-Control Studies; Female; Humans; Hypertension; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Psoriasis; Risk Factors; Sex Factors

Topics: Adolescent; Adult; Aged; Body Mass Index; Female; Humans; Leptin; Male; Middle Aged; Psoriasis; Sex Characteristics

Psoriasis is a multifactorial disease in which genetic and inflammatory factors play important roles. Leptin is classified as a cytokine and plays an important role in the regulation of the T-helper response. A common polymorphism in the promoter of the human leptin gene (G-2548A) may have a role in the pathogenesis of psoriasis.. To investigate the association between psoriasis and leptin gene polymorphism (G-2548A).. The study involved 109 patients with psoriasis and 125 healthy controls. Analyses of G-2548A polymorphism of the leptin gene were made by the polymerase chain reaction-restriction fragment length polymorphism technique. The genotypes (GG, GA, and AA of leptin gene G-2548A) and alleles (G and A) were scored and the frequencies were estimated. The frequencies of alleles and genotypes in patients and controls were compared. The relationship between leptin gene polymorphism and the clinical features of the patients was analyzed.. Both genotype [odds ratio (OR), 0.921; 95% confidence interval (CI), 0.501-1.694; P = 0.792] and allele (OR, 0.864; 95% CI, 0.600-1.242; P = 0.429) frequencies were not significantly different between patient and control groups. In addition, there was no significant association between genotype and allele frequencies and the clinical characteristics of psoriasis.. In this case-control study, no evidence of association between the G-2548A variant of the leptin gene and psoriasis was found.

Topics: Adult; Case-Control Studies; Female; Gene Expression Regulation; Gene Frequency; Genotype; Humans; Leptin; Male; Middle Aged; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Psoriasis; Turkey