leptin and Lupus-Erythematosus--Systemic

Leptin is the forerunner of the adipokine superfamily and plays a key role in regulating energy expenditure and neuroendocrine function. Researches into leptin put emphasize not only on the metabolic role but also its immunoregulatory effect on immune response through immunocyte activation and cytokine secretion. Leptin acts on receptors that are widespread throughout the body and that are expressed across many tissue types. As a consequence, the abnormal expression of leptin has been found to correlate with a number of diseases, including cancers, autoimmune diseases, and cardiovascular diseases. The significance of leptin in the development of autoimmune diseases is becoming increasingly prominent. Systemic lupus erythematosus (SLE) is a severe atypical autoimmune disease that causes damage to multiple organ systems. It is characterised by the following: impaired clearance of apoptotic cells, loss of tolerance to self-antigens, aberrant activation of T cells and B cells, and chronic inflammation. The heightened immunocyte response in SLE means that these physiological systems are particularly vulnerable to regulation by leptin in addition to being of great significance to the research field. Our current review provides insight into the regulatory roles that leptin plays on immune effector cells in SLE.

Topics: B-Lymphocytes; Cytokines; Humans; Inflammation; Leptin; Lupus Erythematosus, Systemic; Macrophages; Neutrophils; T-Lymphocytes, Regulatory; Th17 Cells

We aimed to perform a systematic review and meta-analysis of studies assessing the homeostasis model assessment for insulin resistance (HOMA-IR) values, serum adiponectin, leptin and resistin levels in patients with systemic lupus erythematosus (SLE).. Online databases were searched on 31 March 2019 in order to identify studies comparing HOMA-IR, serum adiponectin, leptin and resistin levels between patients with SLE and controls. A random-effects model was adopted.. Fifty-six studies involving a total of 4460 patients with SLE were included. Patients with SLE had significantly higher HOMA-IR values (standardized mean difference (SMD)=0.425; 95% confidence interval (CI) 0.156-0.693;. Patients with SLE have higher HOMA-IR values and serum levels of adiponectin, leptin and resistin than individuals without SLE. The serum level of resistin correlates with SLE disease activity.

Topics: Adiponectin; Disease Progression; Humans; Insulin Resistance; Leptin; Lupus Erythematosus, Systemic; Resistin; Severity of Illness Index

Topics: Adiponectin; Animals; Atherosclerosis; Humans; Inflammation; Leptin; Lupus Erythematosus, Systemic; Metabolic Syndrome; Risk Factors

The systemic inflammatory nature of systemic lupus erythematosus (SLE) is patent not only in the diverse clinical manifestations of the disease but also in the increased risk of premature cardiovascular diseases (CVD). In this review, we discuss the latest findings on the key factors of the innate immune system known to play critical roles in the pathogenesis of accelerated CVD in patients with SLE and discuss the potential that immunometabolism may play a key role in this respect.. Recent studies exploring the association between SLE and premature CVD clearly showed that alterations of specific immune functions play a pivotal role in the increased cardiovascular morbidity and mortality in the SLE patients. Novel molecular factors such as type I interferons (IFN), dysregulated neutrophil function, and changes to cellular metabolism and metabolites are emerging as important regulators of systemic immune dysfunction and as strong risk factors for premature CVD in SLE. Although corticosteroids and cytotoxic agents can be used to effectively manage and control various lupus-related complications, to date, no drug has been proven to prevent the development of premature atherosclerosis in SLE. However, as new mechanisms underlying this complication of SLE are uncovered, such as the role of metabolism and neutrophil-driven inflammation, new avenues for therapeutic intervention are being discovered.

Topics: Atherosclerosis; Cardiovascular Diseases; Chemokine CCL2; Endothelial Cells; Humans; Immunity, Innate; Inflammation; Interferon Type I; Leptin; Lupus Erythematosus, Systemic; Macrophages; Metabolic Syndrome; Neutrophils; Reactive Oxygen Species

Objective We aimed to evaluate the relationship between circulating leptin levels and systemic lupus erythematosus (SLE). Methods MEDLINE, EMBASE, and Cochrane library databases were searched. Meta-analyses were performed comparing serum/plasma leptin levels in patients with SLE and healthy controls, and on patients with SLE in subgroups based on ethnicity, sample size, data type, and matched variables (age, sex, and/or body mass index (BMI)). Results Eighteen studies including 1333 patients with SLE and 1048 controls were ultimately selected, which showed that leptin levels were significantly higher in the SLE group than in the control group (SMD = 0.611, 95% CI = 0.275-0.947, p < 0.001). When we excluded two outlier studies because of high heterogeneity, leptin levels were also significantly higher in the SLE group than in the control group (SMD = 0.619, 95% CI = 0.431-0.807, p < 0.001). Stratification by ethnicity showed significantly elevated leptin levels in the SLE group in European, Asian, Arab, Latin American, and mixed populations. Subgroup analysis by sample size showed significantly higher leptin levels in the SLE group by small ( n ≤ 100) and large sample numbers ( n > 100) (SMD = 0.780, 95% CI = 0.445-1.115, p < 0.001; SMD = 0.495, 95% CI = 0.275-0.715, p < 0.001). Stratification by data type revealed significantly higher leptin levels in the original data and imputed data groups. Subgroup analysis adjustment revealed significantly higher leptin levels in the SLE group, regardless of adjustment for variables. Conclusions Our meta-analysis demonstrated that leptin levels were significantly higher in patients with SLE, regardless of ethnicity, sample size, data type, and matched variables.

Topics: Case-Control Studies; Humans; Internationality; Leptin; Lupus Erythematosus, Systemic

Leptin is secreted from adipocytes and acts mainly on the hypothalamus causing weight loss due to suppression of appetite and increased energy expenditure. On the other hand, the leptin receptor is also expressed in hematopoietic cells and its action on the immune system has become known, and the significance of leptin in autoimmune diseases has gradually become clear. It has been shown that leptin acts as an exacerbating factor in many autoimmune diseases and it is suggested that inhibition of leptin signal may be a novel therapeutic method for autoimmune diseases. In this article, we will outline the significance of leptin in the immune system based on the current reports.

Topics: Adipocytes; Appetite; Arthritis, Rheumatoid; Autoimmune Diseases; Disease Progression; Energy Metabolism; Hematopoietic Stem Cells; Humans; Hypothalamus; Leptin; Lupus Erythematosus, Systemic; Molecular Targeted Therapy; Receptors, Leptin; Signal Transduction; Weight Loss

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by multisystem organ involvement and unclear pathogenesis. Several adipokines synthesized in the adipose tissue, including leptin, adiponectin, resistin, and chemerin, have been explored in autoimmune rheumatic diseases, especially SLE, and results suggest that these mediators may be implicated in the pathogenesis of SLE. However, the current results are controversial. In this review, we will briefly discuss the expression and possible pathogenic role of several important adipokines, including leptin, adiponectin, resistin, and chemerin in SLE.

Topics: Adipokines; Adiponectin; Adipose Tissue; Animals; Chemokines; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Lupus Erythematosus, Systemic; Molecular Targeted Therapy; Resistin

Currently published data regarding the relationship between plasma/serum leptin levels and systemic lupus erythematosus (SLE) are contradictory. To derive a more precise evaluation of this relationship, a meta-analysis was performed.. Published literature from PubMed, Embase and Cochrane Library were obtained. The study quality was assessed by the Newcastle-Ottawa scale. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effects or random-effect model analysis. Heterogeneity among studies was estimated using the Cochran Q and I(2) statistics.. A total of 11 studies including 868 SLE patients and 591 controls were finally included in the meta-analysis. No significant differences in plasma/serum leptin levels was found between SLE patients and healthy controls when all studies were pooled into the meta-analysis (pooled SMD = 0.269, 95% CI = -0.188 to 0.726). However, subgroup analyses showed that SLE patients from an Asian population, age ≥40 years and BMI <25 had higher plasma/serum leptin levels when compared with controls.. There is no significant difference in plasma/serum leptin levels between the entire group of SLE patients and controls. However, plasma/serum leptin levels are significantly higher in the subgroup of SLE patients from an Asian population ≥40 years of age and with a BMI <25.

Topics: Adult; Asian People; Case-Control Studies; Female; Humans; Leptin; Lupus Erythematosus, Systemic; Male

Leptin, the product of ob gene, is a 16-kDa nonglycosylated peptide hormone produced by adipocytes that regulates appetite and energy expenditure at the hypothalamic level. As is known to be a satiety factor that can regulate body weight by inhibiting food intake and stimulating energy expenditure, leptin is a pleiotropic hormone whose multiple effects include regulation of endocrine function, reproduction and immunity. Since leptin has been considered to be a pro-inflammatory cytokine, investigations of leptin in the pathogenesis of autoimmune diseases have been detected, such as systemic lupus erythematosus, rheumatoid arthritis and osteoarthritis. Recently, the role of leptin in the modulation of immune response and inflammation has been discussed in the autoimmune diseases increasingly but less in systemic lupus erythematosus (SLE). Therefore, this article will focus on the current understanding of the role of leptin with such similar pathogenic mechanism in SLE in order to provide insights which may assist in the development of leptin-based approaches for the treatment of SLE.

Topics: Animals; Anti-Inflammatory Agents; Autoimmunity; Humans; Inflammation Mediators; Leptin; Lupus Erythematosus, Systemic; Molecular Targeted Therapy; Receptors, Leptin; Signal Transduction

To discuss the relationship between adipokines and connective tissue diseases, by putting special emphasis on the potential role of leptin, adiponectin, resistin, and other adipose tissue products in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus and on possible application of adipokine-targeted therapy in the treatment of these disorders with emphasis on the recent findings.. PubMed literature search complemented by review of bibliographies listed in identified articles.. Most of the data presented by different research groups showed changed levels of leptin, adiponectin, and resistin and occasionally also other adipokines in rheumatoid arthritis and systemic lupus erythematosus. The relationship between the remaining connective tissue diseases and adipokines is less documented.. Plasma levels of adipokines might tell us too little about their role in connective tissue disorders, whereas adipokine effects on synovial tissues might differ from their known metabolic or cardiovascular effects, which implies that some re-appraisal of adipokines role may need to take place. It still remains obscure whether the observed disturbances in various adipokine systems in subjects with connective tissue diseases contribute to their development or only reflect the presence or activity of inflammatory process, which itself is induced by other pro-inflammatory factors.

Topics: Adipokines; Adiponectin; Animals; Arthritis, Rheumatoid; Connective Tissue; Disease Models, Animal; Humans; Leptin; Lupus Erythematosus, Systemic; Resistin

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease mainly mediated by IgG autoantibody. While follicular helper T (Tfh) cells are crucial for supporting IgG autoantibody generation in human SLE, underlying mechanisms for Tfh cell mal-differentiation remain unclear.. In total, 129 SLE patients and 37 healthy donors were recruited for this study. Circulating leptin was determined by ELISA from patients with SLE and healthy individuals. CD4 T cells isolated from SLE patients and healthy donors were activated with anti-CD3/CD28 beads under cytokine-unbiased conditions in the presence or absence of recombinant leptin protein, followed by detection for Tfh cell differentiation by quantifying intracellular transcription factor Bcl-6 and cytokine IL-21. AMPK activation was assessed by analyzing phosphor-AMPK using phosflow cytometry and immunoblots. Leptin receptor expression was determined using flow cytometry and its overexpression was achieved by transfection with an expression vector. Humanized SLE chimeras were induced by injecting patients' immune cells into immune-deficient NSG mice and used for translational studies.. Circulating leptin was elevated in patients with SLE, inversely associated with disease activity. In healthy individuals, leptin efficiently inhibited Tfh cell differentiation through inducing AMPK activation. Meanwhile, leptin receptor deficiency was a feature of CD4 T cells in SLE patients, impairing the inhibitory effect of leptin on the differentiation of Tfh cells. As a result, we observed the coexistence of high circulating leptin and increased Tfh cell frequencies in SLE patients. Accordingly, overexpression of leptin receptor in SLE CD4 T cells abrogated Tfh cell mal-differentiation and IgG anti-dsDNA generation in humanized lupus chimeras.. Leptin receptor deficiency blocks the inhibitory effect of leptin on SLE Tfh cell differentiation, serving as a promising therapeutic target for lupus management.

Topics: AMP-Activated Protein Kinases; Animals; Autoantibodies; Humans; Immunoglobulin G; Leptin; Lupus Erythematosus, Systemic; Mice; Receptors, Leptin; T-Lymphocytes, Helper-Inducer

Our previous studies found that serum leptin was increased significantly in SLE, characterised by dysregulated autoreactive B cells producing excessive inflammatory cytokines and autoantibodies. The aim of this study was to explore the effects of leptin on B cell functions in SLE and clarify the key pathways in leptin dysregulated B cells.. Peripheral blood samples were obtained from 86 SLE patients and 28 normal controls. Purified B cells were stimulated with leptin or SLE serum and with or without anti-leptin antibody. The frequencies of CD19-CD138+ plasma cells and the expression of leptin receptor (LEPR) on B cells were determined with flow cytometry. The levels of antibodies and cytokines were assayed by ELISA. Classic signalling pathways were detected with western blotting method.. Increased plasma cells and the levels of IgG and anti-dsDNA antibodies were positively correlated with serum leptin in SLE patients. LEPR+CD19+B cells were increased in SLE patients. Leptin up-regulated LEPR on B cells and activated B cells to produce higher levels of IL-6, IL-10 and TNF-α, and induced B cells to differentiated into plasma cells secreting more IgG and IgM. More importantly, anti-leptin neutralising antibody could partially restore increased cytokines, antibodies and plasma cells induced by SLE serum. Mechanistically, both leptin and SLE serum activated JAK/STAT3/5 and ERK1/2 signalling pathways in B cells, and the secretion-enhancing effects were restored by their inhibitors.. Leptin may be a key factor leading to B cell dysfunction by activating JAK/STAT3/5 and ERK1/2 signalling pathways in SLE.

Topics: Antigens, CD19; B-Lymphocytes; Cytokines; Humans; Immunoglobulin G; Leptin; Lupus Erythematosus, Systemic; MAP Kinase Signaling System; STAT3 Transcription Factor

Ghrelin has been thought of as a potential link between energy homeostasis and fertility. The aim of this study was to evaluate levels of ghrelin in obese and non-obese systemic lupus erythematosus (SLE) patients, and to reveal a possible association between ghrelin and Anti-Mullerian hormone (AMH) in SLE patients.. One hundred SLE patients (50 obese and 50 non-obese subjects) at childbearing age and 100 age-matched healthy controls (50 obese and 50 non-obese subjects) were included. Ghrelin and leptin were examined by enzyme-linked immunosorbent assay. AMH was tested through electrochemiluminescence. Demographics, clinical and laboratory indicators were obtained from medical records.. Ghrelin levels were significantly lower in obese SLE patients than non-obese SLE patients (P = .000) and obese controls (P = .002). Non-obese SLE patients and non-obese controls had similar ghrelin levels. Ghrelin levels were correlated positively with AMH (r = .2683, P = .0070) in SLE patients. And ghrelin were negatively associated with leptin (r = -.1969, P = .0496) and BMI (r = - .2401, P = .0161).. Our results provide evidence for a potential relationship between ghrelin and AMH in SLE patients, indicating that ghrelin may play a part in energy homeostasis and ovarian damage of SLE patients.

Topics: Anti-Mullerian Hormone; Case-Control Studies; China; Female; Ghrelin; Humans; Leptin; Lupus Erythematosus, Systemic; Obesity; Ovarian Reserve

In patients with systemic lupus erythematosus (SLE), a higher frequency of atherosclerotic lesions is associated with poor prognosis. Hydroxychloroquine (HCQ) has been reported to improve the lifespan and the prognosis of dyslipidaemia in patients with SLE, but the mechanism is unclear. We investigated the effect of supplemental HCQ treatment on the levels of serum cytokines associated with atherosclerosis in patients with stable SLE.. Patients with SLE who received supplemental HCQ and maintained low disease activity between January 2016 and September 2020 were included in this study. Disease activity was assessed using Safety of Estrogens in Lupus National Assessment-SLE Disease Activity Index, Cutaneous Lupus Erythematous Disease Area and Severity Index, and Lupus Low Disease Activity State. Serum complement titres, anti-dsDNA antibodies, and serum cytokines (adiponectin, resistin, and leptin) were analyzed before and after HCQ treatment.. Forty-one patients (4 males and 37 females, mean age 41.3 ± 13.2 years) were included. Serum adiponectin levels were significantly increased after 3 months of HCQ treatment compared to baseline, and serum resistin levels were significantly reduced. The change in serum resistin level after HCQ administration was correlated with a significant reduction in serum TNF-α, interleukin (IL)-6, IL-8, and IL-1RA levels.. Supplemental HCQ treatment in patients with SLE improved adipokine levels. HCQ may improve prognosis by controlling disease activity in SLE and reducing risk factors for atherosclerosis. Key Points • Hydroxychloroquine has been reported to improve the prognosis of dyslipidaemia in patients with SLE, but the underlying mechanism is unclear. • In this study, hydroxychloroquine improved adipokine levels in patients with SLE, implicating adipokines as a potential mechanism underlying the benefit of hydroxychloroquine on dyslipidaemia. • Supplemental hydroxychloroquine should be considered in patients with SLE harboring lipid abnormalities and risk factors for atherosclerosis.

Topics: Adipokines; Adiponectin; Adult; Antibodies, Antinuclear; Antirheumatic Agents; Atherosclerosis; Cytokines; Estrogens; Female; Humans; Hydroxychloroquine; Interleukin 1 Receptor Antagonist Protein; Interleukin-8; Leptin; Lipids; Lupus Erythematosus, Systemic; Male; Middle Aged; Resistin; Tumor Necrosis Factor-alpha

Higher body mass and adiposity represent independent contributors to the systemic low-grade inflammatory state often observed in patients with systemic lupus erythematosus (SLE). This study assessed the role of physical fitness in the association of body mass and adiposity with inflammation in women with SLE.. A total of 77 women with SLE were included in this cross-sectional study. We obtained body mass index, waist-to-height ratio, and body fat percentage as indicators of body mass and adiposity. Inflammation was assessed through Serum levels of C-reactive protein, interleukin 6, and leptin. Cardiorespiratory fitness was assessed with the 6-minute walk test, range of motion with the back-scratch test, and muscular strength with handgrip dynamometry.. Cardiorespiratory fitness attenuated the association of both body mass index and body fat percentage with interleukin 6 (all, P<0.05). Range of motion attenuated the association of body mass index with interleukin 6 (P<0.05) and the association of body fat percentage with C-reactive protein (P<0.05). These interactions indicated that higher fitness was associated with a lower increase in inflammation per unit increase of body mass or adiposity. Muscular strength showed a non-significant trend to attenuate the association of body fat percentage with interleukin 6 (P=0.057) but potentiated the association of body fat percentage with leptin (P<0.05).. These findings suggest that higher levels of cardiorespiratory fitness and range of motion might attenuate the impact of higher body mass and adiposity on inflammation in women with SLE. The role of muscular strength requires further investigation.

Topics: Adiposity; Adult; Biomarkers; Body Mass Index; C-Reactive Protein; Cardiorespiratory Fitness; Cross-Sectional Studies; Exercise Tolerance; Female; Functional Status; Hand Strength; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Leptin; Lupus Erythematosus, Systemic; Middle Aged; Range of Motion, Articular; Sex Factors

Both NLRP3 inflammasome and Th17 cells play important roles in the pathogenesis of systemic lupus erythematosus (SLE). Here we tried to investigate whether leptin promotes the differentiation of Th17 cells from lupus mice by activating the NLRP3 inflammasome. Th17 cells induced from MRL/Mp-Fas lpr mice splenocytes under Th17 polarizing condition were treated with leptin at scalar doses during the last 18 h of culture. The mRNA levels of IL-17A, IL-17F, RORγt, IL-1β, IL-18, NLRP3, ASC, and IL-1R1 were detected by quantitative PCR. IL-17A, IL-17F, IL-1β, and IL-18 were tested by ELISA, while the activity of caspase-1 and number of Th17 cells were counted by flow cytometry before/after inhibition of the NLRP3 inflammasome. We found that leptin pushed up the expression of IL-17A, IL-17F, NLRP3, and IL-1β and increased the number of Th17 cells in lupus mice, while the expression of IL-17A, RORγt, and IL-1β and the number of Th17 cells were decreased after inhibition of the NLRP3 inflammasome. Leptin promoted the differentiation of Th17 cells from lupus mice by activating the NLRP3 inflammasome.

Topics: Animals; Cell Differentiation; Cells, Cultured; Cytokines; Disease Models, Animal; Humans; Inflammasomes; Inflammation Mediators; Leptin; Lupus Erythematosus, Systemic; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mice, Inbred MRL lpr; NLR Family, Pyrin Domain-Containing 3 Protein; Th17 Cells

Serum leptin and leptin receptor gene polymorphisms may play a role in the etiopathogenesis of SLE.. This study was undertaken to explore the relationship between serum leptin levels and leptin receptor (LEPR) gene polymorphisms with susceptibility to SLE in Egyptian population and to study their relationships with clinical, laboratory, radiographic findings, and disease activity of SLE (SLEDAI).. A total of 50 unrelated female patients, who met the SLICC classification criteria for SLE and fifty healthy blood donors, matched for age, sex, and BMI with SLE patients, serving as a control group, were included in this study. All participants had completed preliminary questionnaires and clinical, laboratory, and radiographic examinations. Serum leptin levels were measured by ELISA assays. LEPR genotyping was done by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. We compared serum leptin levels and LEPR gene polymorphisms in SLE patients and controls, and we tested their relationships with clinical, laboratory, and radiographic findings and SLEDAI in SLE patients.. The present study showed significant differences of serum leptin levels between SLE patients and controls (p < 0.001). Moreover, higher frequencies of variant genotype (AA) and (A) allele were found in SLE patients compared to controls (p = 0.008 and 0.001, respectively). No associations were observed between the serum leptin, various LEPR genotypes, and gene alleles and the development of clinical, laboratory, and radiological manifestations. Furthermore, no associations were observed between the various LEPR genotypes or gene alleles and leptin levels (p = 0.633 and 0.337 respectively) in SLE patients. Additionally, no correlations were observed between leptin levels, various genotypes, and alleles with SLEDAI (p = 0.244, 0.741, and 0.838 respectively) in SLE patients.. Serum leptin and LEPR gene polymorphism increase risk of SLE in Egyptian population; however, they are not associated with the development of clinical, lab, and radiological findings. Disease activity is neither correlated with serum leptin level nor associated with LEPR gene polymorphism. Serum levels of leptin are not associated with LEPR gene polymorphism. Key Points • Serum leptin and LEPR gene polymorphism increase risk of SLE in Egyptian patients. • Serum leptin is not associated with SLE disease activity.

Topics: Case-Control Studies; Egypt; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Leptin; Lupus Erythematosus, Systemic; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Receptors, Leptin

Saliva is currently used as a reliable diagnostic fluid in a wide range of local and systemic diseases. However, the link between salivary diagnosis and the inflammatory process in autoimmune diseases has not yet been explored. The aim of our study is to assess possible correlations between salivary inflammatory markers and systemic lupus erythematosus (SLE). Patients fulfilling the Systemic Lupus International Collaborating Clinics (SLICC) diagnosis criteria were included. Salivary and serum levels of interleukin-6 (IL-6), leptin, monocyte chemoattractant protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1) were determined using stochastic sensors. Serum leptin and IL-6 had significantly higher levels in SLE patients compared to non-SLE. Also, salivary IL-6 levels highly correlated with the serum IL-6 levels. A positive correlation was found between salivary and serum levels of IL-6, signaling salivary IL-6 as a reliable marker for assessing the inflammation process in SLE.

Topics: Adult; Biomarkers; Case-Control Studies; Chemokine CCL2; Female; Humans; Inflammation; Interleukin-6; Leptin; Lupus Erythematosus, Systemic; Middle Aged; Plasminogen Activator Inhibitor 1; Pregnancy; Pregnancy Complications; Saliva; Serum

Topics: Adipokines; Adiponectin; Adolescent; Adult; Aged; Atherosclerosis; Carotid Intima-Media Thickness; Chemokines; Female; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Lupus Erythematosus, Systemic; Middle Aged; Resistin; Young Adult

Aim To assess subclinical atherosclerosis and the role of inflammatory mediators, vascular endothelial cell activation markers and adipocytokines in systemic lupus erythematosus (SLE) in the presence or absence of metabolic syndrome (MetS). Methods We studied 66 premenopausal female SLE patients (20 with MetS) and 28 female healthy controls (HCs) without history of cardiovascular disease (CVD). Subclinical atherosclerosis was screened by measuring carotid intima media thickness (CIMT). Serum levels of high sensitivity C-reactive protein (hs-CRP), tumour necrosis factor α (TNFα), interleukin 6 (IL-6), soluble intercellular adhesion molecule 1 (sICAM-1), soluble E-selectin, leptin and visfatin were measured. Results The mean age of MetS

Topics: Adult; Atherosclerosis; Biomarkers; Carotid Intima-Media Thickness; Case-Control Studies; Female; Humans; Leptin; Lupus Erythematosus, Systemic; Metabolic Syndrome

Leptin is a well-known adipokine that plays a critical role in immune responses. To further explore the immunological roles of leptin, we developed a transgenic leptin pig controlled by the pig leptin (pleptin) promoter to overexpress leptin. Symptoms typically associated with systemic lupus erythematosus (SLE) were evident in this transgenic pig strain, including anemia, leukopenia, and thrombocytopenia as well as kidney and liver impairment. Histologically, there were increased immunoglobulin G (IgG) levels, elevated antiplatelet antibody (APA) levels, and deposition of immune complexes in the kidney and liver. In addition, anti-double-stranded DNA antibodies (dsDNAs), antinuclear antibodies (ANAs), and antinucleosome antibodies (ANuAs) were all significantly increased in serum immunological examinations. These findings were also accompanied by repression of the regulatory T cell (Treg) ratio. Significantly, glucocorticoid experimental therapies partially relieved the autoimmune responses and bleeding symptoms observed in these transgenic leptin pigs. Together, these results indicate that leptin plays a critical role in the development of autoimmune disorders and demonstrate that our transgenic leptin pigs can act as a valuable model of SLE.

Topics: Animals; Animals, Genetically Modified; Antibodies, Antinuclear; Antigen-Antibody Complex; Autoimmunity; Disease Models, Animal; Immunoglobulin G; Leptin; Lupus Erythematosus, Systemic; Nucleosomes; Promoter Regions, Genetic; Swine; T-Lymphocytes, Regulatory

Leptin levels are increased in patients with systemic lupus erythematosus (SLE) but little is known on how this correlates with several disease characteristics including the frequency of regulatory T cells (Tregs). Here we compared serum leptin levels with frequency of circulating Tregs in 47 lupus patients vs. 25 healthy matched controls. Correlations with lupus disease activity were also analyzed, as well as Treg proliferation potential. It was found that leptin was remarkably increased in SLE patients as compared to controls, particularly in SLE patients with moderate and severe active SLE, and the increase correlated with disease activity. Importantly, increased leptin in lupus patients inversely correlated with the frequency of Tregs but not in controls, and leptin neutralization resulted in the expansion of Tregs ex vivo. Thus, hyperleptinemia in lupus patients correlates directly with disease activity and inversely with Treg frequency. The finding that leptin inhibition expands Tregs in SLE suggests possible inhibition of this molecule for an enhanced Treg function in the disease.

Topics: Adult; Cells, Cultured; Female; Humans; Leptin; Lupus Erythematosus, Systemic; Middle Aged; T-Lymphocytes, Regulatory

There are controversial results about the role of serum leptin and adiponectin levels as biomarkers of the severity of proteinuria in lupus nephritis.. The aim of this study was to evaluate the relationship between serum leptin and adiponectin levels with severity of proteinuria secondary to lupus nephritis (LN).. In a cross-sectional study, 103 women with systemic lupus erythematosus (SLE) were evaluated for kidney involvement. We compared 30 SLE patients with LN, all of them with proteinuria, versus 73 SLE patients without renal involvement (no LN). A comprehensive set of clinical and laboratory variables was assessed, including serum levels of leptin and adiponectin by ELISA. Multivariate analyses were used to adjust for potential confounders associated with proteinuria in LN.. We found higher adiponectin levels in the LN group compared with the no LN group (20.4 ± 10.3 vs 15.6 ± 7.8 μg/mL; p = 0.02), whereas no differences were observed in leptin levels (33.3 ± 31.4 vs 22.5 ± 25.5 ng/mL; p = 0.07). Severity of proteinuria correlated with an increase in adiponectin levels (r = 0.31; p = 0.001), but no correlation was observed with leptin. Adiponectin levels were not related to anti-dsDNA or anti-nucleosome antibodies. In the logistic regression, adiponectin levels were associated with a high risk of proteinuria in SLE (OR = 1.06; 95% CI 1.01-1.12; p = 0.02). Instead, leptin was not associated with LN.. These findings indicate that adiponectin levels are useful markers associated with proteinuria in LN. Further longitudinal studies are required to identify if these levels are predictive of renal relapse.

Topics: Adiponectin; Adult; Biomarkers; Cross-Sectional Studies; Female; Humans; Leptin; Lupus Erythematosus, Systemic; Lupus Nephritis; Middle Aged; Proteinuria; Risk Factors; Severity of Illness Index

To analyze the association of adipokines and tumor necrosis factor α (TNFα) and its receptors with characteristics of systemic lupus erythematosus (SLE) and to investigate the correlation between adipokines and the TNF system.. One hundred and thirty-six SLE women, aged ≥18 years old, were assessed. TNFα, soluble TNFα receptors 1 (sTNFR1) and 2 (sTNFR2) and adipokines were analyzed by ELISA kits.. The median (IQR) of age was 41.5 (33.0-49.7) years old and of disease duration 11.3 (7.8-15.8) years. The median (IQR) of disease activity was 0 (0-4) and of damage index was 2 (1-3). Higher levels of sTNFR1 and sTNFR2 were associated with nephritis (p < 0.001 for both), and sTNFR1 (p = 0.025) and TNFα (p = 0.014) were positively associated with arthritis. Higher sTNFR1 levels were found in participants that were not using antimalarial drugs (p = 0.04). Independent correlation was found between sTNFR1 (β = 0.253; p = 0.003) and sTNFR2 (β = 0.297; p < 0.001) levels and disease activity and damage index (sTNFR1: β = 0.367; p < 0.001; sTNFR2: β = 0.335; p < 0.001). Higher adiponectin levels were independently associated with nephritis (p = 0.009) and antimalarial drugs use (p = 0.015). There was a positive correlation between leptin and sTNFR2 levels (p = 0.002) and between resistin levels and sTNFR1 (p < 0.001) and sTNFR2 (p < 0.001).. The correlation between adipokines and TNF system allows a better understanding of the role of adipokines in the inflammatory response in SLE patients.

Topics: Adipokines; Adult; Antimalarials; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Lupus Erythematosus, Systemic; Lupus Nephritis; Middle Aged; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; Resistin; Severity of Illness Index; Tumor Necrosis Factor-alpha

To explore the association of LEP and leptin receptor (LEPR) gene single-nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE) in a Chinese population. Four LEP SNPs (rs11761556, rs12706832, rs2071045 and rs2167270) and nine LEPR SNPs (rs10749754, rs1137100, rs1137101, rs13306519, rs8179183, rs1805096, rs3790434, rs3806318 and rs7518632) were genotyped in a cohort of 633 patients with SLE and 559 healthy controls. Genotyping of SNPs was performed with improved multiple ligase detection reaction (iMLDR). No significant differences were detected for the distribution of allele and genotype frequencies of all 13 SNPs between patients with SLE and controls. The genotype effects of recessive, dominant and additive models were also analysed, but no significant evidence for association was detected. However, further analysis in patients with SLE showed that the TT genotype and T allele frequencies of the LEP rs2071045 polymorphism were nominally significantly higher in patients with pericarditis (P = 0.012, P = 0.011, respectively). In LEPR, the GA/AA genotype and A allele frequencies of the rs1137100 polymorphism were both nominally associated with photosensitivity in patients with SLE (P = 0.043, P = 0.018, respectively). Moreover, the genotype and allele distribution of rs3806318 were also nominally associated with photosensitivity in patients with SLE (P = 0.013, P = 0.008, respectively). No significant differences in serum leptin levels were observed in patients with SLE with different genotypes. In summary, LEP and LEPR SNPs are not associated with genetic susceptibility to SLE, but may contribute to some specific clinical phenotype of this disease; further studies are necessary to elucidate the exact role of LEP and LEPR genes in the pathogenesis of SLE.

Topics: Adult; Asian People; Case-Control Studies; Demography; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Haplotypes; Humans; Leptin; Lupus Erythematosus, Systemic; Male; Polymorphism, Single Nucleotide; Receptors, Leptin; Risk Factors

Crescent literature data demonstrated a role of adipokines in immune responses, particularly leptin is involved in wide spectrum of pro-inflammatory functions. Several evidences suggested that leptin is able to inhibit T regulatory cells proliferation and function in vitro models. In the present study, we investigate the relationship between leptin and circulating T regulatory cells (Tregs) in patients affected by systemic lupus erythematosus (SLE).. 13 SLE patients and 11 healthy controls were enrolled. Metabolic syndrome and cardiovascular parameters were evaluated. Serum leptin levels were detected by commercial ELISA kit and circulating regulatory T cells were determined by FACS analysis as CD4+CD25highFOP3+ lymphocytes.. Metabolic syndrome, defined by ATPIII criteria, was more prevalent in SLE compared to controls (38.4% vs. 0%, p = 0.04), as well as arterial hypertension (38.4% vs. 0%, p = 0.04). We did not find significant differences in mean leptin levels among SLE and controls (13.13 ± 1.51 ng/ml vs. 9.48 ± 8.67 ng/ml, p = 0.6). Mean Tregs percentage of total CD4 were 1.27 ± 0.9 in SLE vs. 2.8 ± 1.2 in healthy controls (p = 0.001). We found a negative correlation between leptin levels and Tregs percentage of total CD4 in SLE patients (r = 0.4, p = 0.01).. Our results suggest a role of leptin in the regulation of circulating T regulatory cells amount in human SLE.

Topics: Adipokines; Adult; Biomarkers; CD4-Positive T-Lymphocytes; Cell Proliferation; Cohort Studies; Female; Humans; Leptin; Lupus Erythematosus, Systemic; Lymphocyte Activation; Male; Metabolic Syndrome; Middle Aged; T-Lymphocytes, Regulatory

Leptin is an adipocytokine that plays a key role in the modulation of immune responses and the development and maintenance of inflammation. Circulating levels of leptin are elevated in systemic lupus erythematosus (SLE) patients, but it is not clear whether this association can reflect a direct influence of leptin on the propathogenic events that lead to SLE. To investigate this possibility, we compared the extent of susceptibility to SLE and lupus manifestations between leptin-deficient (ob/ob) and H2-matched leptin-sufficient (wild-type, WT) mice that had been treated with the lupus-inducing agent pristane. Leptin deficiency protected ob/ob mice from the development of autoantibodies and renal disease and increased the frequency of immunoregulatory T cells (Tregs) compared with leptin-sufficient WT mice. The role of leptin in the development of SLE was confirmed in the New Zealand Black (NZB) × New Zealand White (NZW)F1 (NZB/W) mouse model of spontaneous SLE, where elevated leptin levels correlated with disease manifestations and the administration of leptin accelerated development of autoantibodies and renal disease. Conversely, leptin antagonism delayed disease progression and increased survival of severely nephritic NZB/W mice. At the cellular level, leptin promoted effector T-cell responses and facilitated the presentation of self-antigens to T cells, whereas it inhibited the activity of regulatory CD4 T cells. The understanding of the role of leptin in modulating autoimmune responses in SLE can open possibilities of leptin-targeted therapeutic intervention in the disease.

Topics: Animals; Autoantibodies; Autoimmunity; Disease Models, Animal; Humans; Immunity, Innate; Inflammation; Leptin; Lupus Erythematosus, Systemic; Mice; Mice, Inbred NZB; T-Lymphocytes, Regulatory; Terpenes

Topics: Humans; Leptin; Lupus Erythematosus, Systemic

Topics: Adiponectin; Humans; Inflammation; Leptin; Lupus Erythematosus, Systemic

Systemic lupus erythematosus (SLE) and lupus nephritis (LN) have strong concomitance with cardiovascular disease that cannot be explained fully by typical risk factors. We examined the possibility that serum or urine expression of adipokines may act as biomarkers for LN, as these proteins have been associated previously with cardiovascular disease as well as SLE. Antibody arrays were performed on serum and urine from lupus patients and matched controls using a cross-sectional study design. From the initial array-based screening data of 15 adipokines, adiponectin, leptin and resistin were selected for validation by enzyme-linked immunosorbent assay (ELISA). Correlations were determined between adipokine expression levels and measures of disease activity or lupus nephritis. The expression of adiponectin and resistin was increased in both sera and urine from LN patients, while leptin was increased in LN patient sera, compared to matched controls. Serum resistin, but not urine resistin, was correlated with measures of renal dysfunction in LN. Serum resistin expression may be useful as a marker of renal dysfunction in patients with LN, although longitudinal studies are warranted. Further studies are necessary to determine if resistin has functional consequences in LN.

Topics: Adiponectin; Adult; Biomarkers; Cross-Sectional Studies; Disease Progression; Enzyme-Linked Immunosorbent Assay; Female; Humans; Kidney; Leptin; Lupus Erythematosus, Systemic; Lupus Nephritis; Male; Protein Array Analysis; Resistin; Up-Regulation

The study is conducted to evaluate relationship between LEPRQ223R (Gln > Arg) polymorphism, serum leptin levels, soluble leptin receptor (SOb-R) levels and SLE risk in Kashmiri population.LEPR genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 100 unrelated SLE patients and equal number of healthy control subjects. Leptin and SOb-R levels were measured by ELISA assays. The present study showed higher frequency of variant genotype (AG + GG) in cases compared to controls [OR = 2.52, CI = 1.18-5.35, p = 0.03]. Moreover the rare (G) allele was significantly more predominant in cases than controls [OR = 1.49, p = 0.04]. Interestingly a positive association between the variant genotype and the development of arthritis [OR = 11.8, CI = 1.6-85.1, p = 0.002] and an inverse association with cardiac disorder [OR = 0.09, CI = 0.02-0.46, p = 0.001] was observed in this study. Furthermore the study showed significant differences of leptin levels in SLE patients and controls (23.9 ± 19.5 vs 14.8 ± 10.4, p < 0.001). SLE patients in the highest quartile leptin levels (≥32.5 ng/mL) were significantly more likely to have higher BMI (p = 0.001) and increased risk of developing arthritis (p = 0.02). Furthermore positive association was observed between the variant genotype(AG + GG) and leptin levels (p = 0.001) in SLE patients. Thus, it is evident from our study that LEPRQ223R polymorphism and elevated leptin levels are associated with increased susceptibility of SLE in Kashmiri population.

Topics: Adult; Alleles; Case-Control Studies; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; India; Leptin; Lupus Erythematosus, Systemic; Male; Middle Aged; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Receptors, Leptin; Risk; Risk Factors; Young Adult

Cardiovascular disease (CVD) has emerged as an important cause of death in patients with systemic lupus erythematosus (SLE). Reduced adiponectin and elevated leptin levels may contribute to CVD in SLE patients. The purpose of this study was to verify the effects of fish oil (FO) on adiponectin and leptin in patients with SLE. Biochemical and disease activity analysis were performed. Patients with SLE were divided in two groups: patients who used fish oil for four months and patients who did not use fish oil. Patients with SLE who used FO had a significant decrease in SLE disease activity index (SLEDAI) score (p ˂ 0.023) in relation to baseline. SLE patients who used fish oil had increased adiponectin levels (p ˂ 0.026) and decreased leptin levels (p ˂ 0.024) compared to baseline values, whereas there were no differences in adiponectin and leptin levels in patients with SLE who did not use fish oil. In conclusion, the findings of increased serum adiponectin an decreased leptin levels after 120 days in the fish oil group, reinforce the importance of evaluating prospective studies of fish and fish oil fish ingestion on these adipokines in an attempt to decrease cardiovascular risk factors in patients with SLE.

Topics: Adiponectin; Adult; Anthropometry; Biomarkers; Blood Pressure; Fatty Acids, Omega-3; Female; Fish Oils; Humans; Leptin; Lupus Erythematosus, Systemic; Male; Middle Aged; Prospective Studies

Mesenchymal stem cells (MSCs) derived from patients with systemic lupus erythematosus (SLE) exhibit enhanced senescence. Cellular senescence has been reported to be induced by several inflammatory cytokines, including interferon-α (IFNα) and IFNγ, that are involved in the pathogenesis of SLE. We undertook this study to investigate whether the inflammatory environment in SLE could affect MSC senescence.. Cellular senescence was measured by staining of senescence-associated β-galactosidase and by expression of the cell cycle inhibitors p53 and p21. Eighty cytokines and chemokines in serum from healthy controls and patients with SLE were identified by cytokine antibody array.. SLE serum promoted senescence of MSCs, which was reversed by the phosphatidylinositol 3-kinase (PI3K)/Akt signaling inhibitor LY294002 but not by the JAK/STAT inhibitor AG490 and not by the MEK/ERK inhibitor PD98059. Cytokine antibody array analysis revealed that leptin and neutrophil-activating peptide 2 (NAP-2) were the 2 factors most significantly elevated in SLE serum compared with normal serum. Blockade of leptin or NAP-2 in MSC cultures abolished SLE serum-induced senescence, while direct addition of these 2 factors could promote senescence in cultures of normal MSCs. Inhibition of PI3K/Akt signaling with LY294002 reduced leptin- and NAP-2-induced senescence in MSCs.. Taken together, our data show that leptin and NAP-2 act synergistically to promote MSC senescence through enhancement of the PI3K/Akt signaling pathway in SLE patients.

Topics: Adult; Case-Control Studies; Cellular Senescence; Chromones; Cytokines; Enzyme Inhibitors; Female; Flavonoids; Humans; Janus Kinases; Leptin; Lupus Erythematosus, Systemic; MAP Kinase Signaling System; Mesenchymal Stem Cells; Morpholines; Peptides; Phosphatidylinositol 3-Kinase; Phosphoinositide-3 Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Signal Transduction; STAT Transcription Factors; Tyrphostins; Young Adult

Leptin is abnormally elevated in the plasma of patients with systemic lupus erythematosus (SLE), where it is thought to promote and/or sustain pro-inflammatory responses. Whether this association could reflect an increased genetic susceptibility to develop SLE is not known, and studies of genetic associations with leptin-related polymorphisms in SLE patients have been so far inconclusive. Here we genotyped DNA samples from 15,706 SLE patients and healthy matched controls from four different ancestral groups, to correlate polymorphisms of genes of the leptin pathway to risk for SLE. It was found that although several SNPs showed weak associations, those associations did not remain significant after correction for multiple testing. These data do not support associations between defined leptin-related polymorphisms and increased susceptibility to develop SLE.

Topics: Case-Control Studies; Genetic Predisposition to Disease; Genotype; Humans; Leptin; Lupus Erythematosus, Systemic; Polymorphism, Single Nucleotide

Previous studies have indicated that leptin and the soluble leptin receptor (SLR) might influence inflammatory and immune processes in autoimmune diseases, but this remains unclear in systemic lupus erythematosus (SLE). The aim of our study was to assess if leptin and SLR are involved in the etiopathology of SLE and the possible mechanism of immune regulation. We studied 87 patients with SLE and 85 matched subjects. We assessed the levels of serum leptin and SLR, tested the long isoform leptin receptor (Ob-Rb) mRNA levels in SLE patients and a control group. Furthermore, we measured Th1 and Th2 percentage in SLE patients' lymphocytes and examined lymphocytes activation and proliferation assays with leptin stimulation in vitro. The study found a higher level of serum leptin in SLE patients, however, no difference was found in serum SLR levels or Ob-Rb mRNA levels between SLE patients and the control group. The percentage of Th1 cells decreased and Th2 cells increased after treatment with glucocorticoids in SLE patients. Leptin stimulated the proliferation of T cells in vitro, and differentiation to Th1 cells increased. The present study demonstrated that leptin may play an important role in the pathogenesis of SLE, inducing dysfunction of autoimmune processes.

Topics: Adolescent; Adult; Aged; Asian People; Cell Proliferation; Female; Flow Cytometry; Humans; Leptin; Lupus Erythematosus, Systemic; Lymphocyte Activation; Lymphocyte Count; Male; Middle Aged; Prospective Studies; Receptors, Leptin; RNA, Messenger; Th1 Cells; Th2 Cells; Young Adult

Leptin is secreted by adipocytes, the placenta, and the stomach. It not only controls appetite through leptin receptors in the hypothalamus, it also regulates immunity. In the current study, we produced leptin-deficient MRL/Mp-Fas(lpr) mice to investigate the potential role of leptin in autoimmunity. C57BL/6J-ob/ob mice were backcrossed with MRL/Mp-Fas(lpr) mice, which develop human systemic lupus erythematosus (SLE)-like lesions. The effects of leptin deficiency on various SLE-like manifestations were investigated in MRL/Mp-Fas(lpr) mice. The regulatory T cell population in the spleen was analyzed by flow cytometry, and the effects of leptin on regulatory T cells and Th17 cells were evaluated in vitro. Compared with leptin-producing MRL/Mp-Fas(lpr) mice, leptin-deficient MRL/Mp-Fas(lpr) mice showed less marked splenomegaly and a particularly low population of CD3(+)CD4(-)CD8(-)B220(+) T cells (lpr cells). Their serum concentrations of Abs to dsDNA were lower, and renal histological changes at age 20 wk were ameliorated. Regulatory T cells were increased in the spleens of leptin-deficient MRL/Mp-Fas(lpr) mice. Leptin suppressed regulatory T cells and enhanced Th17 cells in vitro. In conclusion, blockade of leptin signaling may be of therapeutic benefit in patients with SLE and other autoimmune diseases.

Topics: Animals; Antibodies, Antinuclear; Autoantigens; Cells, Cultured; Crosses, Genetic; DNA; Female; Immunoglobulin G; Kidney; Leptin; Lupus Erythematosus, Systemic; Lymphocyte Count; Male; Mice, Inbred C57BL; Mice, Inbred MRL lpr; Mice, Obese; Rheumatoid Factor; Signal Transduction; Specific Pathogen-Free Organisms; Spleen; Splenomegaly; T-Lymphocyte Subsets; T-Lymphocytes, Regulatory; Th17 Cells

An increased frequency of atherosclerosis (ATH) in systemic lupus erythematosus (SLE) is well-documented but not fully explained by the presence of traditional cardiac risk factors. Several nontraditional biomarkers, including proinflammatory high-density lipoprotein (piHDL) and leptin, have been individually associated with subclinical ATH in SLE. The aim of this study was to examine whether these and other biomarkers can be combined into a risk profile, the Predictors of Risk for Elevated Flares, Damage Progression, and Increased Cardiovascular Disease in Patients with SLE (PREDICTS), that could be used to better predict future progression of ATH.. In total, 210 patients with SLE and 100 age-matched healthy control subjects (all women) participated in this prospective cohort study. The longitudinal presence of carotid plaque and intima-media thickness (IMT) were measured at baseline and followup (mean ± SD 29.6 ± 9.7 months).. At followup, carotid plaque was present in 29% of SLE patients. Factors significantly associated with plaque, determined using Salford Predictive Modeling and multivariate analysis, included age ≥48 years (odds ratio [OR] 4.1, P = 0.002), high piHDL function (OR 9.1, P < 0.001), leptin levels ≥34 ng/dl (OR 7.3, P = 0.001), plasma soluble TWEAK levels ≥373 pg/ml (OR 28.8, P = 0.004), and history of diabetes (OR 61.8, P < 0.001). Homocysteine levels ≥12 μmoles/liter were also a predictor. However, no single variable demonstrated an ideal combination of good negative predictive values (NPVs), positive predictive values (PPVs), sensitivity, and specificity. A high-risk PREDICTS profile was defined as ≥3 positive biomarkers or ≥1 positive biomarker plus a history of diabetes; for high-risk SLE patients, the PPV was 64%, NPV was 94%, sensitivity was 89%, and specificity was 79%. In multivariate analysis, SLE patients with the high-risk profile had 28-fold increased odds for the longitudinal presence of plaque (P < 0.001) and increased progression of IMT (P < 0.001).. A high-risk PREDICTS score confers 28-fold increased odds of the presence of any current, progressive, or acquired carotid plaque, both in patients with SLE and in control subjects, and is significantly associated with higher rates of IMT progression.

Topics: Adiponectin; Adult; Age Factors; Apolipoprotein A-I; Atherosclerosis; Biomarkers; Carotid Arteries; Carotid Artery Diseases; Carotid Intima-Media Thickness; Case-Control Studies; Cholesterol, HDL; Cholesterol, LDL; Cohort Studies; Cytokine TWEAK; Diabetes Complications; Diabetes Mellitus; Disease Progression; Female; Homocysteine; Humans; Leptin; Longitudinal Studies; Lupus Erythematosus, Systemic; Middle Aged; Multivariate Analysis; Odds Ratio; Plaque, Atherosclerotic; Predictive Value of Tests; Prospective Studies; Risk Assessment; Risk Factors; Sensitivity and Specificity; Tumor Necrosis Factors

In systemic lupus erythematosus (SLE), the availability of self-antigen promotes and fuels self-reactive immune responses. Apoptotic cells represent a major source of self-antigens, and an impairment of the removal of apoptotic material containing self-antigen can contribute to the development of autoimmunity. To address whether the adipocytokine leptin--which favors autoimmune responses through little understood mechanisms--could modulate the handling of apoptotic cells in SLE, we evaluated the ability of leptin to modulate the capacity of macrophages to phagocytose apoptotic bodies in (NZB × NZW)F1 lupus mice. It was found that leptin promoted phagocytosis of apoptotic cells by macrophages by modulating cAMP levels in macrophages. This finding associated with an increased availability of antigen that favored the development of T cell responses to apoptotic-derived antigen. As leptin promotes macrophage phagocytosis of apoptotic bodies in SLE and subsequent availability of apoptotic-derived antigen to T cells, an inhibition of this process via leptin blockade might have a therapeutic potential in SLE.

Topics: Animals; Apoptosis; Autoantigens; Autoimmunity; Cell Line; Cyclic AMP; Disease Models, Animal; Female; Leptin; Lupus Erythematosus, Systemic; Lymphocyte Activation; Macrophages; Mice; Mice, Transgenic; Phagocytosis; T-Lymphocytes

Th17 CD4(+) cells promote inflammation and autoimmunity. In this study, we report that Th17 cell frequency is reduced in ob/ob mice (that are genetically deficient in the adipokine leptin) and that the administration of leptin to ob/ob mice restored Th17 cell numbers to values comparable to those found in wild-type animals. Leptin promoted Th17 responses in normal human CD4(+) T cells and in mice, both in vitro and in vivo, by inducing RORγt transcription. Leptin also increased Th17 responses in (NZB × NZW)F1 lupus-prone mice, whereas its neutralization in those autoimmune-prone mice inhibited Th17 responses. Because Th17 cells play an important role in the development and maintenance of inflammation and autoimmunity, these findings envision the possibility to modulate abnormal Th17 responses via leptin manipulation, and they reiterate the link between metabolism/nutrition and susceptibility to autoimmunity.

Topics: Animals; CD4-Positive T-Lymphocytes; Disease Models, Animal; Gene Expression Regulation; Humans; Leptin; Lupus Erythematosus, Systemic; Mice; Mice, Knockout; Nuclear Receptor Subfamily 1, Group F, Member 3; Receptors, Leptin; Th17 Cells; Transcription, Genetic

In systemic lupus erythematosus (SLE), the impairment in apoptosis can facilitate the initiation and maintenance of autoimmune responses to self antigens. Here we show that the adipocytokine leptin, which is abnormally elevated in SLE, promotes the survival and proliferation of autoreactive T-cells in mice with an autoreactive T-cell repertoire, including (NZB x NZW)F1 lupus-prone mice. This ability of leptin to promote lupus T-cell autoimmunity suggests the possibility of a therapeutic targeting of leptin in SLE.

Topics: Animals; Apoptosis; Autoantibodies; Autoimmunity; Cells, Cultured; Dexamethasone; Leptin; Lupus Erythematosus, Systemic; Lymphocyte Activation; Mice; Mice, Inbred NZB; Mice, Transgenic; Thymocytes

The purpose of the present study was to determine levels of adipokines and their relationship with stiffness parameters and disease activity index in SLE patients in comparison with healthy controls. Sixty SLE patients and 29 control subjects were enrolled in the study. Serum leptin and adiponectin levels were determined by commercial sandwich ELISA kits. Colour-coded carotid duplex sonography was performed using a Siemens SONOLINE Antares machine equipped with linear 5-13 MHz. SLEDAI, ECLAM and SLICC were evaluated in all patients. Data were analysed by software for statistical analysis (Prism 5.0). Median leptin is higher among SLE patients compared with controls (p 0.035). Median values of vascular stiffness and PSEM are increased in SLE compared with controls (p = 0.0003 and p = 0.007). Vascular strain and vascular distensibility are lower in SLE patients in comparison with controls (p = 0.0001 and p = 0.0006, respectively). Considering SLE patients, leptin levels correlate with vascular stiffness (r = 0.64, p < 0.0001) and PSEM (r = 0.63, p < 0.0001). Adiponectin levels correlate with vascular strain (r = 0.28, p 0.039) and negatively correlate with vascular stiffness (r = -0.38, p 0.039). Leptin levels correlate with disease activity (SLEDAI and ECLAM) and cumulative damage (SLICC) indexes. This study demonstrates higher values of leptin in SLE patients. Moreover, SLE patients show increased levels of vascular stiffness and PSEM and reduced values of vascular strain and distensibility. These results globally indicate a decline in arterial elasticity. We find a positive correlation of leptin with stiffness parameters. According to its atheroprotective action, adiponectin inversely correlates with stiffness parameters.

Topics: Adiponectin; Adult; Female; Humans; Leptin; Lupus Erythematosus, Systemic; Middle Aged; Vascular Stiffness

Fasting is beneficial in the prevention and amelioration of the clinical manifestations of autoimmune diseases including systemic lupus erythematosus. The mechanisms responsible for these effects are not well understood. During fasting, there is a dramatic reduction of the levels of circulating leptin, an adipokine with proinflammatory effects. Leptin also inhibits CD4(+)CD25(+)Foxp3(+) regulatory T cells, which are known to contribute significantly to the mechanisms of peripheral immune tolerance. In this study, we show that fasting-induced hypoleptinemia in (NZB × NZW)F(1) lupus-prone mice induced an expansion of functional regulatory T cells that was reversed by leptin replacement. The specificity of the findings was indicated by the lack of these effects in leptin-deficient ob/ob mice and leptin receptor-deficient db/db mice. These observations help to explain the beneficial effects of fasting in autoimmunity and could be exploited for leptin-based immune intervention in systemic lupus erythematosus.

Topics: Animals; Cell Differentiation; Fasting; Female; Genetic Predisposition to Disease; Leptin; Lupus Erythematosus, Systemic; Mice; Mice, Inbred C57BL; Mice, Inbred NZB; Mice, Obese; Receptors, Leptin; Starvation; T-Lymphocytes, Regulatory

Although metabolic syndrome (MS) and systemic lupus erythematosus (SLE) are often associated, a common link has not been identified. Using the BWF1 mouse, which develops MS and SLE, we sought a molecular connection to explain the prevalence of these two diseases in the same individuals. We determined SLE- markers (plasma anti-ds-DNA antibodies, splenic regulatory T cells (Tregs) and cytokines, proteinuria and renal histology) and MS-markers (plasma glucose, non-esterified fatty acids, triglycerides, insulin and leptin, liver triglycerides, visceral adipose tissue, liver and adipose tissue expression of 86 insulin signaling-related genes) in 8-, 16-, 24-, and 36-week old BWF1 and control New-Zealand-White female mice. Up to week 16, BWF1 mice showed MS-markers (hyperleptinemia, hyperinsulinemia, fatty liver and visceral adipose tissue) that disappeared at week 36, when plasma anti-dsDNA antibodies, lupus nephritis and a pro-autoimmune cytokine profile were detected. BWF1 mice had hyperleptinemia and high splenic Tregs till week 16, thereby pointing to leptin resistance, as confirmed by the lack of increased liver P-Tyr-STAT-3. Hyperinsulinemia was associated with a down-regulation of insulin related-genes only in adipose tissue, whereas expression of liver mammalian target of rapamicyn (mTOR) was increased. Although leptin resistance presented early in BWF1 mice can slow-down the progression of autoimmunity, our results suggest that sustained insulin stimulation of organs, such as liver and probably kidneys, facilitates the over-expression and activity of mTOR and the development of SLE.

Topics: Animals; Antibodies, Antinuclear; Biomarkers; Body Weight; Cytokines; Disease Models, Animal; Feeding Behavior; Female; Gene Expression Regulation; Humans; Insulin; Intra-Abdominal Fat; Leptin; Liver; Lupus Erythematosus, Systemic; Metabolic Syndrome; Mice; Proteinuria; TOR Serine-Threonine Kinases; Triglycerides

Patients with systemic lupus erythematosus (SLE) are at increased risk of atherosclerosis, even after accounting for traditional risk factors. High levels of leptin and low levels of adiponectin are associated with both atherosclerosis and immunomodulatory functions in the general population.. To examine the association between these adipokines and subclinical atherosclerosis in SLE, and also with other known inflammatory biomarkers of atherosclerosis.. Carotid ultrasonography was performed in 250 women with SLE and 122 controls. Plasma leptin and adiponectin levels were measured. Lipoprotein a (Lp(a)), oxidised phospholipids on apoB100 (OxPL/apoB100), paraoxonase, apoA-1 and inflammatory high-density lipoprotein (HDL) function were also assessed.. Leptin levels were significantly higher in patients with SLE than in controls (23.7±28.0 vs 13.3±12.9 ng/ml, p<0.001). Leptin was also higher in the 43 patients with SLE with plaque than without plaque (36.4±32.3 vs 20.9±26.4 ng/ml, p=0.002). After multivariate analysis, the only significant factors associated with plaque in SLE were leptin levels in the highest quartile (≥29.5 ng/ml) (OR=2.8, p=0.03), proinflammatory HDL (piHDL) (OR=12.8, p<0.001), age (OR=1.1, p<0.001), tobacco use (OR=7.7, p=0.03) and hypertension (OR=3.0, p=0.01). Adiponectin levels were not significantly associated with plaque in our cohort. A significant correlation between leptin and piHDL function (p<0.001), Lp(a) (p=0.01) and OxPL/apoB100 (p=0.02) was also present.. High leptin levels greatly increase the risk of subclinical atherosclerosis in SLE, and are also associated with an increase in inflammatory biomarkers of atherosclerosis such as piHDL, Lp(a) and OxPL/apoB100. High leptin levels may help to identify patients with SLE at risk of atherosclerosis.

Topics: Adipokines; Adult; Atherosclerosis; Biomarkers; Body Mass Index; Carotid Artery, Common; Epidemiologic Methods; Female; Humans; Inflammation Mediators; Leptin; Lipids; Lupus Erythematosus, Systemic; Middle Aged; Oxidation-Reduction; Ultrasonography

Elevated serum leptin levels have been described in patients with systemic lupus erythematosus (SLE), however these studies have provided no information regarding the ghrelin levels. We investigated the clinical significance of serum leptin and ghrelin levels in SLE. The leptin levels of SLE patients were higher than those of normal healthy controls, while the ghrelin levels of the SLE were lower. In addition, the ghrelin levels were significantly lower in SLE patients with arthritis and hematologic disorder. Taken together, these findings suggest that leptin and ghrelin play a role in clinical manifestations observed in SLE.

Topics: Adult; Arthritis; Asian People; Case-Control Studies; Female; Ghrelin; Hematologic Diseases; Humans; Korea; Leptin; Lupus Erythematosus, Systemic; Male; Prospective Studies; Young Adult

Atherosclerosis is accelerated in people with systemic lupus erythematosus, and the presence of dysfunctional, pro-inflammatory high-density lipoproteins is a marker of increased risk. We developed a mouse model of multigenic lupus exposed to environmental factors known to accelerate atherosclerosis in humans - high-fat diet with or without injections of the adipokine leptin. BWF1 mice were the lupus-prone model; BALB/c were non-autoimmune controls. High-fat diet increased total serum cholesterol in both strains. In BALB/c mice, non-high-density lipoprotein cholesterol levels increased; they did not develop atherosclerosis. In contrast, BWF1 mice on high-fat diets developed increased quantities of high-density lipoproteins as well as elevated high-density lipoprotein scores, indicating pro-inflammatory high-density lipoproteins; they also developed atherosclerosis. In the lupus-prone strain, addition of leptin increased pro-inflammatory high-density lipoprotein scores and atherosclerosis, and accelerated proteinuria. These data suggest that environmental factors associated with obesity and metabolic syndrome can accelerate atherosclerosis and disease in a lupus-prone background.

Topics: Animals; Atherosclerosis; Diet; Dietary Fats; Disease Models, Animal; Female; Humans; Leptin; Lipoproteins, HDL; Lupus Erythematosus, Systemic; Metabolic Syndrome; Mice; Mice, Inbred BALB C; Mice, Inbred NZB; Obesity; Risk Factors

To study concentrations of adipokines in patients with systemic lupus erythematosus (SLE) and the relationship among adipokines, the metabolic syndrome (MeS), and cardiovascular disease (CVD) risk factors.. We enrolled 50 SLE patients and 26 controls, all women. Leptin, resistin, visfatin, and adiponectin were measured by commercial ELISA kits.. MeS prevalence was increased among subjects with SLE. Leptin levels were higher in patients with SLE than controls. Among SLE patients, independent determinants of leptin were insulin levels (p < 0.0001), triglycerides (p = 0.03), body mass index (p = 0.02), corticosteroid dosage (p = 0.02), and SLE Disease Activity Index (p = 0.005). Other adipokines did not differ between SLE patients and controls.. Leptin was increased in SLE patients and could play a role in SLE-related cardiovascular diseases.

Topics: Adipokines; Adiponectin; Adrenal Cortex Hormones; Adult; Biomarkers; Body Mass Index; Comorbidity; Cytokines; Female; Humans; Immunosuppressive Agents; Insulin; Leptin; Lupus Erythematosus, Systemic; Metabolic Syndrome; Nicotinamide Phosphoribosyltransferase; Predictive Value of Tests; Resistin; Triglycerides; Up-Regulation

Patients with SLE are at risk for premature atherosclerosis and metabolic syndrome. Cytokines produced by adipocytes, adipokines, are important in glucose/lipid metabolism and the development of atherosclerosis. The objectives of this study were to evaluate leptin, adiponectin and ghrelin concentrations in paediatric SLE (pSLE) and to correlate these concentrations with measures of disease activity, serum lipid concentrations, measures of insulin resistance and serum homocysteine concentrations.. Two hundred and eight samples from 105 patients with pSLE and 77 samples from 77 healthy paediatric controls were evaluated by ELISA to measure leptin, adiopnectin and ghrelin. Students' t-test was used for analysis. Concentrations of adipokines were correlated with disease activity, serum lipids, insulin resistance and homocysteine.. Overall 35 SLE patients (34%) had an abnormally elevated leptin level. The only significant correlation of leptin concentrations was with homocysteine concentrations but not disease activity, prednisone dose, lipids or insulin resistance. There was no difference in the mean adiponectin concentrations between the control and patient groups and none of the patient samples were below the normal lower limit while seven were elevated. There was a significant correlation of adiponectin concentrations with prednisone dose, lipid concentrations and insulin resistance but not with disease activity or homocysteine. Elevated ghrelin concentrations were found in 20% of the pSLE patients. The only correlation of ghrelin concentrations was with homocysteine.. Adipokines are novel biomarkers in pSLE. They may represent cardiovascular risk and are not just surrogate markers for disease activity, therapy or serum lipids. Their correlation with atherosclerosis needs to be explored.

Topics: Adipokines; Adiponectin; Adolescent; Biomarkers; Child; Child, Preschool; Cohort Studies; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Female; Ghrelin; Glucocorticoids; Homocysteine; Humans; Insulin Resistance; Leptin; Lipids; Lupus Erythematosus, Systemic; Male; Prednisone; Severity of Illness Index

We tested the hypothesis that concentrations of adipocytokines are altered in SLE and associated with coronary atherosclerosis, insulin resistance and inflammation. Concentrations of resistin, leptin, adiponectin and visfatin were measured in 109 patients with SLE and 78 control subjects. Coronary calcification was measured using electron beam-computed tomography, and insulin resistance was defined by the homeostasis model assessment index. Concentrations of adiponectin (28.7 +/- 17.9 vs 22.0 +/- 15.3 microg/mL, P = 0.003), leptin (41.1 +/- 49.9 vs 19.8 +/- 24.6 ng/mL, P < 0.001) and visfatin (7.5 +/- 10.5 vs 4.5 +/- 2.8 ng/mL, P < 0.001) were higher in patients with SLE than in controls. These differences remained significant after adjustment for age, race, sex and body mass index (BMI; all P values < 0.02). Concentrations of resistin (10.7 +/- 7.6 vs 9.1 +/- 5.1 ng/mL, P = 0.41) did not differ in patients and controls. In patients with SLE, leptin was positively associated with BMI (rho = 0.80, P < 0.001), insulin resistance (rho = 0.46, P < 0.001) and C-reactive protein (CRP) (rho = 0.30, P = 0.002), whereas adiponectin was negatively associated with the same factors (rho = -0.40, P < 0.001; rho = -0.38, P < 0.001; rho = -0.22, P = 0.02, respectively). None of the adipocytokines were associated with coronary atherosclerosis in SLE. In conclusion, patients with SLE have increased concentrations of adiponectin, leptin and visfatin. Lower concentrations of adiponectin and higher concentrations of leptin are associated with insulin resistance, BMI and CRP in patients with SLE.

Topics: Adipokines; Adiponectin; Adult; Body Mass Index; C-Reactive Protein; Case-Control Studies; Coronary Artery Disease; Cross-Sectional Studies; Female; Humans; Inflammation; Insulin Resistance; Leptin; Lupus Erythematosus, Systemic; Male; Metabolic Syndrome; Middle Aged; Nicotinamide Phosphoribosyltransferase; Resistin; Risk Factors

In patients with systemic lupus erythematosus (SLE) metabolic alterations are often observed, which may be due to either the disease, the genetic background or the treatment. We studied the serum levels of the adipokines leptin, adiponectin, resistin, visfatin and ghrelin in patients with SLE and controls. Leptin levels were lower and adiponectin, ghrelin and visfatin levels were higher in the patients. No significant differences were encountered for resistin. The values of adipokines were independent of treatment, even after correction for body mass index. Inverse correlations were found among leptin and adiponectin, ghrelin and visfatin. We conclude that adipokines are involved in the metabolic imbalance of patients with SLE.

Topics: Adiponectin; Adult; Body Mass Index; Female; Ghrelin; Humans; Leptin; Lupus Erythematosus, Systemic; Male; Nicotinamide Phosphoribosyltransferase; Resistin

Leptin, a peptide hormone, plays an essential role in the regulation of body weight, the endocrine function, reproduction, the immune response and inflammation. The immune system, in turn, modifies leptin's production. Systemic lupus erythematosus (SLE) is an autoimmunological disease characterized by widespread inflammation with possible involvement of each body organ and system. In this study, we assessed serum leptin levels in SLE patients and the control group in search for correlations between leptin concentrations and other markers' level, the activity of the disease, its duration, the age of the patients and their bone mineral density. Blood samples were collected from 30 SLE and 30 control group women. Each SLE patient was matched with one from the control for age (+/-1 year) and the body mass index (BMI; +/-1). Serum leptin levels were determined using the DRG Leptin ELISA Kit. Serum leptin levels in SLE patients ranged from 1.8 to 66.3 ng/ml (median value 7.5), and in control group it was 8.8 ng/ml (0.7-39.2) (NS). In SLE, serum leptin levels (after the logarithmic transformation) correlated with BMI (r = 0.89, P < 0.0001), the age (r = 0.34, P < 0.01) and the patients' disease duration (r = 0.59, P < 0.0005). Serum leptin levels in SLE patients with arthritis (P < 0.05) and central nervous system (CNS) involvement (P = 0.05) were significantly lower in comparison with serum leptin levels in SLE patients without arthritis and CNS involvement. No correlation was found between serum leptin levels and the T-score. In the control group, the logarithmic transformation of serum leptin levels positively correlated with BMI (r = 0.52, P < 0.05). No differences in serum leptin levels were shown between SLE patients and the control group. However, we found correlation between BMI and serum leptin levels in both groups. Furthermore, serum leptin levels in SLE patients with arthritis and CNS involvement were significantly lower in comparison with SLE patients without arthritis and CNS involvement, which suggests that active chronic inflammation may lower plasma leptin concentrations.

Topics: Adult; Body Mass Index; Case-Control Studies; Female; Humans; Leptin; Lupus Erythematosus, Systemic; Middle Aged; Severity of Illness Index

This study was done to evaluate the relation between the level ofleptin, prolactin, IL-4 and IL-5 with the activity of Rheumatoid Arthritis (RA) and Lupus erythematosus (SLE). The study included 33 patients divided into two groups. Group 1 included twenty-one patients with Juvenile rheumatoid arthritis (13 males and 8 females) with age 11.9 +/- 3.6 years and twelve patients with systemic lupus erythematosus were enrolled as group 2 (2 males and 10 females) with age 15.8 +/- 2.9 years. Twenty-one healthy children with matched age, sex and anthropometrics measures were included in the study to serve as control group (group 3). There were significant increases in the levels of Leptin (<0.038), Prolactin (p < 0.021) IL-4 (p < 0.005) in Juvenile Rheumatoid Arthritis group with insignificant decrease in IL-5 (p < 0.724) in comparison to control group. Systemic Lupus group show a significant increase in level of Leptin (p < 0.05), Prolactin (p < 0.02) and IL-4 (p < 0.000) with an insignificant increase in IL-5 (p < 0.685) in comparison to control group. RA patients show a positive significant correlation between Prolactin, IL-5 and activity with negative insignificant correlation between IL-4 and activity. Where in Lupus patients there was a positive significant correlation between Prolactin, IL-4 and activity with negative insignificant correlation between IL-5 and activity. There was no correlation between Leptin and activity in both diseases (RA, SLE). There's a highly significant positive correlation between serum Leptin levels and BMI among all patients of RA and Lupus (p < 0.000, p < 0.003), respectively. There was a difference in the Leptin level between male and female patients with a significant increase in the female than male (p < 0.05). We can conclude from our results that Leptin cannot be used to assess disease activity in RA and SLE where Prolactin can be used to assess disease activity in RA and SLE.

Topics: Adolescent; Arthritis, Juvenile; Biomarkers; Body Mass Index; Case-Control Studies; Child; Female; Humans; Interleukin-4; Interleukin-5; Leptin; Lupus Erythematosus, Systemic; Male; Prolactin; Sex Characteristics

The metabolic syndrome, closely associated with cardiovascular disease, is characterized by increased insulin resistance (IR). Although accelerated atherosclerosis is frequently observed in systemic lupus erythematosus (SLE), the prevalence and significance of IR remain to be elucidated. We evaluated IR in association with plasma concentrations of adipocytokines in patients with SLE.. Outpatients with SLE (n = 37) and healthy controls (n = 80) were studied. A value of the homeostasis model assessment index (HOMA-IR) > 2.0 was considered to be IR. Plasma concentrations of adiponectin and tumor necrosis factor-a (TNF-a) were measured by ELISA and leptin by radioimmunoassay.. HOMA-IR indices of the SLE patients were significantly higher than those of controls (2.3 +/- 2.3 vs 1.3 +/- 1.0, respectively; p < 0.01), although both groups exhibited a similar body mass index. The prevalence of hypertension and diabetes mellitus was significantly higher in patients with SLE compared with controls (48.6% vs 8.8% and 10.8% vs 0%). Twelve SLE patients (32%) with IR exhibited significantly higher incidence of hypertension and current proteinuria than SLE patients without IR. Plasma leptin, TNF-a, and, unexpectedly, adiponectin levels were higher in SLE patients than controls (adiponectin, 13.7 +/- 5.0 vs 9.5 +/- 3.9 microg/ml). Among the SLE patients, patients with IR showed significantly lower adiponectin levels than patients without IR (10.9 +/- 4.6 vs 15.4 +/- 4.4 microg/ml). Serum levels of adiponectin were significantly correlated inversely with HOMA-IR in SLE patients.. Elevated levels of adiponectin in SLE, despite inverse correlation with IR, suggest the possible involvement of adiponectin in IR and alterations in its effect on insulin sensitivity.

Topics: Adiponectin; Adult; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hypertension; Leptin; Lupus Erythematosus, Systemic; Male; Metabolic Syndrome; Outpatients; Radioimmunoassay; Tumor Necrosis Factor-alpha

Accumulating data indicate that metabolic syndrome is an inflammatory condition. Systemic lupus erythematosus (SLE) is an autoimmune disorder associated with nephritis and cardiovascular disease. Evidence suggests that individuals with SLE are at risk for developing insulin resistance; however, this has not been directly examined. Using an established mouse strain with SLE (NZBWF1), we examined whether SLE is associated with increased body weight and fat deposition. Mean arterial pressure was significantly increased (140+/-4 versus 114+/-2 mm Hg; n > or = 5) in SLE mice by 36 weeks of age compared with control mice (NZW/LacJ). Body weight in SLE mice was higher at each age compared with controls by 12%, 22%, and 34% (n > 30). Visceral adipose tissue weight was increased in SLE by 44%, 74%, and 117% at 8, 20, and 36 weeks, respectively (n > or = 12). Plasma leptin was increased in SLE mice (8.6+/-1.0 versus 24.7+/-2.2 ng/mL; n = 5), and renal and adipose tissue exhibited macrophage infiltration. Fasted insulin was higher in SLE mice (0.6+/-0.1 versus 1.4+/-0.3 ng/mL; n > or = 10), but fasted glucose was not different (94+/-5 versus 80+/-9; n > or = 9). A glucose tolerance test caused a significantly greater and longer increase in blood glucose from mice with SLE compared with control mice. Food intake was not different between control and SLE mice. However, mice with SLE demonstrated lower levels of nighttime activity than controls. These data show that the NZBWF1 strain may be an important model to study the effects of obesity and insulin resistance on SLE-associated hypertension.

Topics: Animals; Disease Models, Animal; Female; Hypertension; Insulin Resistance; Leptin; Lupus Erythematosus, Systemic; Metabolic Syndrome; Mice; Mice, Inbred NZB; Obesity

Hypoandrogenicity is common in obesity and in chronic inflammatory diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Adrenal androgens such as androstenedione (ASD) and dehydroepiandrosterone (DHEA) sulphate are low, which partly depends on the influence of TNF in chronic inflammatory diseases. Leptin is stimulated by TNF and is associated with hypoandrogenicity in non-inflammatory conditions.. To study the interrelation between serum levels of leptin and adrenal steroids in SLE and RA.. In a retrospective study, serum levels of leptin, ASD, DHEA, and 17-hydroxyprogesterone (17OHP) were measured by ELISA, and serum levels of cortisol by radioimmunoassay in 30 patients with RA, 32 with SLE, and 54 healthy control subjects (HS).. In SLE and RA but not HS, serum levels of ASD correlated negatively with serum levels of leptin (p<0.01) independently of prior prednisolone treatment in patients with SLE (p = 0.013) and tended to be independent of prednisolone in patients with RA (p = 0.067). In a partial correlation analysis, this interrelation remained significant after controlling for daily prednisolone dose in both patient groups. In both patient groups, serum leptin levels correlated negatively with the molar ratio of serum ASD/serum cortisol and serum ASD/serum 17OHP, and positively with the molar ratio of serum DHEA/serum ASD.. The negative correlation of serum leptin and ASD or, particularly, ASD/17OHP, together with its known anti-androgenic effects indicate that leptin is also involved in hypoandrogenicity in patients with SLE and RA. Leptin may be an important link between chronic inflammation and the hypoandrogenic state.

Topics: 17-alpha-Hydroxyprogesterone; Adult; Androgens; Androstenedione; Arthritis, Rheumatoid; Case-Control Studies; Dehydroepiandrosterone Sulfate; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hydrocortisone; Leptin; Lupus Erythematosus, Systemic; Male; Radioimmunoassay; Retrospective Studies

The purpose of this study was to evaluate serum leptin levels in systemic lupus erythematosus (SLE). Forty-one women with SLE were compared with 23 healthy women of similar age and body mass index (BMI). Clinical characteristics and Mexican systemic lupus erythematosus disease activity index (Mex-SLEDAI) score were assessed. Serum leptin levels (ng/dl) were measured by enzyme-linked immunosorbent assay (ELISA). Comparisons of leptin levels were made with the Mann-Whitney U-test. In a multiple regression analysis, those factors that could influence the leptin levels were adjusted. Patients with SLE had higher leptin levels than the control group (SLE median 31 vs control median 15, P=0.023). After adjusting by other variables, the serum leptin levels remained higher in SLE than in controls (P=0.02). Patients with SLE had no association between leptin levels and Mex-SLEDAI score, age, duration of disease, or prednisone doses. Those with SLE had higher leptin levels than controls. Further longitudinal studies are required to evaluate the role of this hormone in the exacerbations of SLE.

Topics: Adult; Age Factors; Anthropometry; Biomarkers; Body Mass Index; Case-Control Studies; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Lupus Erythematosus, Systemic; Middle Aged; Probability; Prognosis; Reference Values; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Statistics, Nonparametric