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Background In current intensive care treatment, there are patients with severe burns who cannot be saved due to progressive organ failure. Further investigation of the pathogenesis of severe burns is needed to improve the mortality rate. In burns, inflammatory cytokines form a network that leads to an inflammatory response. Adipocytes secrete physiologically active substances (adipokines). The roles of adipokines have not been completely clarified in burn patients. This study aimed to determine the relation between serial changes of adipokines and clinical course in severely burned patients. Methods This was a single-center, retrospective, observational study. Patients’ blood samples were collected on the day of injury and around 1 week later. Adipokines (adiponectin, angiotensinogen, chemerin, CXCL-12/SDF-1, leptin, resistin, vaspin, visfatin), various inflammatory cytokines, syndecan-1 and C1 esterase inhibitor were measured. Results Thirty-eight patients were included. Resistin levels were significantly higher in the non-survivors versus survivors on Day 1 after burn injury. Hierarchical clustering analysis showed common clusters on Day 1 and at 1 Week after burn injury (resistin, IL-6, IL-8, IL10 and MCP-1). The correlation coefficient of resistin to SOFA score at 1 Week was significant. Logistic regression analysis showed a significant relation of resistin levels on Day 1 with prognosis; the area under the ROC curve for resistin was 0.801. Conclusions In the acute phase of burns, resistin was associated with other pro-inflammatory cytokines and was related to the severity and prognosis of major burns.

Objective Smoking is a common public problem leading to increases in oxidative stress and decreases in the levels of some micronutrients, finally affecting adipokine levels. The aim of this study was to compare the serum levels of omentin (intelectin-1), chemerin, TNF-α, and some micronutrient intakes in male smokers and non-smokers. Methods 40 male smokers and 40 male non-smokers with a mean age of 38.6 ± 14.1 years were included in this study. Serum levels of omentin, chemerin, and TNF-α were measured. To calculate the daily intake of energy, carbohydrate, protein, fat, and some of the micronutrients, the 24-h recall and semi-quantitative food frequency questionnaire (FFQ) was used. Results Omentin, chemerin, and TNF-α levels in male smokers were lower than non-smokers, but these differences were not statistically significant. However, after adjustment for total and saturated fat intakes and age, omentin (β = 138.4, p = 0.027) and TNF-α (β = 144.5, p = 0.015) revealed significant differences. Conclusion The serum levels of omentin, chemerin, TNF-α, and some micronutrient intakes were not significantly different between smokers and non-smokers. Further population studies are needed to clarify this subject.

The differential diagnosis of psoriatic arthritis (PsA) and rheumatoid arthritis (RA) is difficult because of the lack of diagnostic clinical signs and reliable biomarkers. This study investigated microRNAs (miRNA) and adipokines as potential additional markers to discriminate PsA from RA. The expression profile of miRNA (miR-21, miR-140, miR-146a, miR-155, miR-181b, miR-223, miR-let-7e) and inflammatory cytokines (IL-1β, IL-6, IL-17a, IL-23a, TNF-α) from peripheral blood mononuclear cells of PsA and RA patients compared to healthy controls (HC) were evaluated by real-time PCR, and serum adipokines (adiponectin, chemerin, leptin, resistin, visfatin) and cytokines by ELISA assay. Univariable binary logistic regression was used to find the association between PsA and potential predictors. The gene expression of miRNA and cytokines and the serum levels of adipokines were found significantly different in PsA and RA patients compared to HC, as well as in PsA versus RA. MiR-140 gene expression resulted up-regulated in PsA patients and reduced in RA in comparison to HC, and, for the first time, significantly higher in PsA compared with RA. Serum levels of IL-23a and leptin were significantly increased in PsA and RA populations than in HC, as well as in PsA versus RA. Furthermore, circulating TNF-α was up-regulated in PsA and RA in comparison to controls, while resulted higher in RA than in PsA. Univariable binary logistic regression analysis found the above-mentioned markers associated to PsA versus RA. Our results first demonstrated an increased expression of circulating miR-140 and serum leptin in PsA patients compared to RA, which were identified as potential additional biomarkers to discriminate PsA from RA. Since the differential diagnosis of PsA and RA poses challenges in clinical practice, our data may help to enhance the diagnostic performance of PsA in daily practice.

Polycystic ovarian syndrome (PCOS) is the main cause of infertility in women. It is frequently associated with reduced progesterone production by human luteinised granulosa cells (hlGCs). However, the molecular mechanisms involved in these steroidogenesis alterations in PCOS patients are unclear. In a dihydrotestosterone-induced PCOS mouse model, steroid production is maintained in the setting of chemokine-like receptor 1 (Cmklr1) knockout. Thus, chemerin and chemerin receptors in terms of expression and progesterone regulation could be different in control and PCOS hlGCs. We first confirmed that progesterone levels in both plasma (P < 0.0001) and follicular fluid (FF) (P < 0.0001) were significantly reduced in PCOS normal weight women compared to control women. These data were associated with a lower STAR mRNA expression in both in vivo (P < 0.0001) and in vitro (P < 0.0001) hlGCs from PCOS women. Secondly, chemerin FF levels (P < 0.0001) and RARRES2 (P < 0.05) and CMKLR1 (P < 0.0001) mRNA levels in GCs were higher in PCOS normal weight patients. Thirdly, treatment of hlGCs with a specific nanobody (the VHH CA4910) targeting the human receptor for CMKLR1 leading to its inactivation abolished chemerin-induced progesterone inhibition, suggesting the involvement of CMKLR1 in this process. Furthermore, the inhibition of progesterone secretion induced by chemerin was two-fold higher in PCOS hlGCs (P < 0.05). Moreover, the VHH CA4910 reinstated a normal progesterone secretion with lower concentrations in PCOS hlGCs, suggesting a different chemerin sensitivity between PCOS and control hlGCs. Thus, chemerin, through CMKLR1, could be involved in the steroidogenesis alterations in PCOS hlGCs.

Objective: Turner syndrome (TS) patients are at high risk of cardiometabolic disorders. Cardiometabolic risk factors are more commonly related to visceral rather than total body adiposity. Adipocytokines have been explored as a potential link between obesity and obesity-related cardiometabolic dysfunction. This study explored the validity of epicardial fat-thickness (EFT) and perihepatic fat-thickness (PHFT) measurement as cardiometabolic-risk predictors in TS-girls in relation to standard obesity-indices and metabolic syndrome (MetS) components. Methods: Forty-six TS girls and twenty-five controls (10-16 years) were subdivided into two age-groups (10 to less than 13 and 13-16). Participants were assessed for body mass index (BMI) Z-scores, waist circumference (WC), total-fat mass (FM) and trunk-FM by bioimpedance-technique, EFT and PHFT by cardiovascular magnetic resonance, lipid-profile, homeostasis model assessment of insulin resistance (HOMA-IR), and serum chemerin. MetS was defined according to International Diabetes Federation criteria. Results: Overweight/obesity and MetS were detected in 45.7% and 37% of TS-girls respectively. BMI Z-score, WC, total-FM, trunk-FM, EFT and PHFT values were significantly higher in TS-age groups compared to age-matched control groups, being more pronounced in the older group when TS-girls had been exposed to estrogen. Dyslipidemia, higher HOMA-IR, chemerin, EFT and PHFT values were observed in lean-Turner compared to BMI-Z-matched controls. EFT and PHFT were significantly correlated with chemerin and several components of MetS. EFT at a cut-off-value of 6.20 mm (area under the curve=0.814) can predict MetS in TS-girls. Conclusion: TS-girls displayed an adverse cardiometabolic profile during late childhood and adolescence. EFT and PHFT are emerging cardiometabolic risk predictors in TS-patients. Excess EFT rather than total body adiposity may contribute to altered metabolic profile among lean-Turner patients.

Background. Diabetic retinopathy (DR) is a prevalent microvascular complication of diabetes, and the levels of chemerin were associated with the severity of DR. However, there is no research on chemerin in the development of proliferative diabetic retinopathy (PDR). Therefore, our study aimed to explore the relationship between chemerin and PDR. Methods. The levels of chemerin/chemokine-like receptor (CMKLR1), proinflammatory cytokines, and vascular endothelial growth factor (VEGF) in 90 cases of PDR and nonproliferative diabetic retinopathy (NPDR) patients and in high glucose (HG) stimulated human retinal pigment epithelium cells (ARPE-19) were evaluated by ELISA. Moreover, chemerin was added into HG-induced ARPE-19 cells to assess its effect on proinflammatory cytokines and VEGF. Results. The levels of chemerin/CMKLR1 were higher in PDR patients than NPDR ones, and chemerin was positively correlated with CMKLR1 in PDR patients. Compared to NPDR, the secretions of proinflammatory cytokines and VEGF were increased in PDR patients and positively correlated with chemerin/CMKLR1. Additionally, chemerin activated CMKLR1 and aggravated HG-induced cell injury, inflammatory responses, and VEGF expressions in ARPE-19 cells. Conclusion. Our study demonstrated that chemerin/CMKLR1 axis aggravated the progression of PDR, which suggested that inhibition of chemerin might serve as a new therapeutic approach to treat PDR.

Background The adipokines, secreted from adipose tissue or body fats, are also called adipocytokines which are cytokines, cell signaling proteins or cell–cell communication. However, AF is a common cardiac arrhythmia in which the heart beats so fast by abnormal beating and is a serious public health disease associated with increased heart failure, systemic thromboembolism, and death. Adipokines are cardiovascular disease (CVD) mediators or biomarkers that affect the heart as well as blood vessels, by increasing the cardiac contractility and action potential duration, which result in the extent of left ventricular and atrial remodeling. Main body Google Scholar, PubMed, and science direct were used to review the literature. Many keywords were used for searching the literature such as Adipokines, Leptin, Apelin, Adiponectin, Omentin-1, Chemerin, CTRP3, TNF-α, IL-6, IL-10, and AF. According to the literature, much more data are available for numerous adipokines, but this review article only has taken few major adipokines which played their major role in Atrial Fibrillation. The review article did not limit the time frame. Conclusion In conclusion, adipokines play a significant role in the development and progress of atrial fibrillation. Also, there are major adipokines such as adiponectin, apelin, C1q/TNF-Related Protein 3 (CTRP3), Chemerin, Omentin-1, interleukin-6, Leptin, TNF-α, resistin, and interleukin-10, which played their pathophysiological role in atrial fibrillation by causing cardiac hypertrophy, increasing the cardiac contractility and action potential duration, atrial fibrosis, electrical and structural remodeling of atrial tissue.

Data about the influence of short-term lifestyle intervention in children with obesity on long-term follow-up body weight, adipokines and cardiometabolic risk parameters is scarce.In a subgroup of the LOGIC-trial (Long-term Effects of Lifestyle Intervention in Obesity and Genetic Influence in Children), we assessed anthropometry (BMI, BMI-SDS (Standard Deviation Score), adipokines (omentin-1, chemerin, leptin, adiponectin) and cardiometabolic risk parameters, (e.g. hsCRP) in children with overweight/obesity after 4 weeks of lifestyle intervention (n = 156, 14.0 ± 1.8 yrs) and after one year follow-up (n = 50). Data were compared to normal weight children (JuvenTUM school cohort; n = 152, 13.3 ± 0.7 yrs).Short-term lifestyle intervention was associated with a significant reduction in BMI and BMI-SDS (p 0.001), with significant reductions in hsCRP, leptin, and chemerin levels, and an increase in adiponectin and omentin-1 levels (p 0.001 for all). After one year follow-up a significant reduction in BMI and BMI-SDS was observed in children from the LOGIC-trial (p 0.001). Improvements in adiponectin (p = 0.025) and chemerin levels (p = 0.027) were seen in children with clear weight loss success (BMI-SDS reduction ≥ 0.2), whereas children with no or only mild weight loss success showed an increase in leptin levels (p 0.001). An increase in omentin-1 levels was observed after 1 year independent of weight change (p 0.001).Effects of short-term weight reduction on mean BMI and BMI-SDS persist over one year. Improvements in omentin-1 levels were independent of short-term or long-term weight loss.ClinicalTrials.gov: LOGIC-trial: NCT01067157, JuvenTUM-trial: NCT00988754.

Osteoarthritis (OA) is considered the most common degenerative joint pathology in the adult population, being an important cause of disability worldwide, and its prevalence is increasingly associated with different factors, including obesity. Obesity together with metabolic syndrome have been associated with a pro-inflammatory state due to the release of cytokines that induce changes in cartilage metabolism. Chemerin is an adipokine secreted mainly by adipocytes and its final action is to increase the production of IL-6, IL-8, IL-1b, TNF-a and metalloproteinases by macrophages, dendritic cells and chondrocytes, which are responsible for damage to the articular cartilage. This is one of the reasons that obesity and inflammation have been linked to OA. The main objective of this study is to determine whether the serum chemerin concentrations of a group of patients with primary OA are higher when compared with control individuals. A further purpose of the study is to determine the relationship between the presence of obesity/overweight with the severity of the disease measured by a radiological scale.An analytical cross-sectional study was carried out where serum chemerin levels were quantified by enzyme-linked immunoadsorption assay (ELISA), in patients with primary OA of the hip, knee and hand with criteria from the ACR (American College Of Rheumatology) and controls. Radiological studies of patients and controls were analysed to determine the severity of joint involvement using the Kellgren and Lawrence (KL) classification system. The statistical significance of the difference in serum chemerin values between the two groups was verified and the correlation between the variables of body mass index (BMI) with radiological severity, number of joint regions and serum chemerin levels was analysed.During the period from July 2015 to July 2016, serum samples and radiographs of compromised joints were collected from 40 patients with primary OA who met the inclusion criteria, as well as serum samples from 20 controls. The average concentration of chemerin was higher in the group of patients with OA compared to that of the control group, being 373ng / ml and 175.55ng / ml respectively (p2.2×10-16). No significant associations were found between the different degrees of disease severity measured by the KL radiological scale, such as the number of involved joint regions and BMI.In a group of patients with primary OA of the hand, knee or hip, the values of chemerin were higher than those found in controls, without significant association with the severity of the disease established radiologically by K/L scale, the number of involved joint regions, and the BMI.

The aim of this study was to investigate the effect of Lactobacillus reuteri E81 (LRE) probiotic supplementation on heat stress responses in chukar partridges (Alectoris chukar). The birds were divided into two groups, one of which was exposed to heat stress (HS). Within each group, four subgroups, each including 64 birds, were created for the three treatment doses (200, 400 or 600 mg/kg) of LRE and the control. The experiment was started with day-old birds, kept at a temperature of 25 °C or 37 °C. After a 7-day adjustment period, the LRE supplementation lasted for 35 days. The levels of different adipokines, including visfatin (VF), adiponectin (ADP), chemerin (CHEM), as well as the concentration of plasma citrulline (CIT) and the levels of thyroid hormones (T3 and T4) and thyroid-stimulating hormone (TSH) in the blood were measured at 21 and 42 days of age. A significant correlation (P < 0.01) was found between LRE supplementation and the decrease in serum VF, ADP, CIT, T3 and T4 levels in partridges exposed to HS. On the other hand, no significant relationship was found between LRE supplementation and the serum CHEM and TSH levels (P > 0.05). We concluded that the addition of 600 mg/kg LRE is beneficial in preventing intestinal damage and inflammation provoked by HS.

In obese patients, the relationship between the content of chemerin in blood plasma and the expression of genes TFAM, Drp1, MFN2, SOD, BAX, responsible for quality control of mitochondria, in insulin-dependent tissues (adipose tissue, liver) was revealed. The tissue-specific features of gene expression (TFAM, Drp1, MFN2, SOD, BAX), the number of mtDNA copies in the studied depots in obese patients were established. It has been proven that a change (decrease) in the number of mtDNA copies in insulin-dependent tissues can have a protective effect on mitochondria under conditions of increased oxidative stress. It was found that in patients without type 2 diabetes, an increase in chemerin production promotes the activation of the antioxidant system in the visceral adipose tissue but not in the liver. On the contrary, all obese patients with type 2 diabetes showed a decrease (compared with patients without type 2 diabetes) in the plasma level of chemerin. Thus, the low content of chemerin in the blood plasma in patients with type 2 diabetes mediates the formation of mitochondrial dysfunction in insulin-dependent tissues (adipose tissue, liver).

Research question Can the adipocytokine milieu of the follicular niche improve the ability to predict treatment outcomes in infertile patients? Design Follicular fluid samples from overweight patients were analysed and compared with samples from matched normal-weight patients. Concentrations of adiponectin, chemerin, C-reactive protein, interleukin-6 (IL-6), IL-10, IL-18, insulin, leptin, prolactin, resistin, tumour necrosis factor alpha (TNF-α) and bone morphogenetic protein-15 (BMP-15) were assessed by multiple magnetic bead immunoassay (MMBI) and enzyme-linked immunosorbent assay and correlated with fertility treatment outcomes. Results Analysis of samples from 22 overweight and 22 normal-weight patients demonstrated that TNF-α can predict oocyte maturation rate. When stratified by body mass index (BMI), IL-10 emerges as a better predictor of oocyte maturation in normal-weight patients. Prolactin was a negative predictor for fertilization rate in the full cohort, and this prediction power was lost upon stratification. No adipocytokines were predictive of blastulation rate, and only age remained predictive. BMP-15 was a strong predictor of high-quality blastulation in the full cohort, more so in the normal-weight population. Conclusions The adipocytokine milieu of the follicular fluid provides a snapshot of the growing oocyte's environment and can help predict fertility treatment outcomes, fine-tuning understanding of the dysregulation caused by increasing BMI. Inflammatory cytokines can predict oocyte maturation; prolactin, oocyte competence; and BMP-15, high-quality blastulation. Further analysis of these findings with a larger sample size and assessing individual oocytes will help shed more light on the clinical significance of these findings.

A body of studies has examined the circulating concentration of adipokines including apelin, vapin, resistin, and chemerin in polycystic ovary syndrome (PCOS) patients. However, their findings have been inconclusive. Therefore, we systematically reviewed available studies to illuminate the overall circulating concentration of adipokines in PCOS subjects. Cochrane’s Library, PubMed, Scopus, and ISI Web of Science databases were searched from the earliest available date up to April 2021 for relevant articles. The quality of each study was assessed by the Newcastle–Ottawa Quality Assessment Scale. The pooled effect size was estimated based on the random effects model, and the standard mean differences (SMD) with a 95% confidence interval (CI) were reported. A total of 88 studies met the inclusion criteria and were included in the current systematic review and meta-analysis. The results of the analysis showed that serum levels of vaspin (SMD 0.69; 95% CI, 0.22 to 1.17; P = 0.004; I2 = 90.6%), chemerin (SMD 1.87; 95% CI, 1.35 to 2.40; P

Recent studies have revealed that fatty tissue, so far considered an energy storage organ, is also the source of many substances called adipokines, including chemerin which plays many important functions in the body. Chemerin stimulates adipocytes maturation and differentiation, as well as acts as a chemoattractant, which stimulates innate and acquired immunity. This adipokine participates in the early stages of acute inflammation as well as its suppression by reacting with the CMKLR1 receptor. In various diseases associated with inflammatory processes, the level of chemerin in the serum increases. It is also considered a marker for benign and malignant tumors. Explanation of the pathomechanisms involving this adipokine is of a high importance and may contribute to the development of new possibilities in the treatment of many diseases. The article presents the latest information on the role of chemerin in various pathological states, particularly in psoriasis.

A higher ratio of M1/M2 macrophages and an elevated chemerin level are both related to increased risk of preeclampsia. However, the crosstalk between these two events and their collective contribution to preeclampsia are not well understood. In this study, we assessed the impacts of chemerin chemokine-like receptor 1 (CMKLR1)/p-Akt/CEBPα axis in regulating macrophage polarization and mediating the pathogenic effects of chemerin on preeclampsia. We showed that chemerin, in a dose- and time-dependent manner, stimulated M1 macrophage polarization, inhibited macrophage-induced trophoblast invasion and migration, and suppressed macrophage-mediated angiogenesis. All these chemerin-induced phenotypes are essentially mediated by sequentially CMKLR1, Akt activation, and CEBPα. Mechanistically, CEBPα acted as a transcriptional activator for both IRF8 and chemerin. In vivo, chemerin aggravated preeclampsia, while α-NETA, an inhibitor for CMKLR1, significantly suppressed M1 macrophage polarization and alleviated preeclampsia. In summary, chemerin, by activating CMKLR1/Akt/CEBPα axis, forms a positive feedback loop, promotes M1 macrophage polarization, suppresses trophoblast migration/invasion and angiogenesis, and contributes to preeclampsia. Therefore, targeting chemerin signaling may benefit the prevention and/or treatment of preeclampsia.

Background and Purpose: Unstable carotid plaques are a common cause of ischemic strokes. Identifying markers that reflect/contribute to plaque instability has become a prominent focus in cardiovascular research. The adipokines, resistin and chemerin, and ChemR23 (chemerin receptor), may play a role in carotid atherosclerosis, making them potential candidates to assess plaque instability. However, the expression and interrelationship of resistin and chemerin (and ChemR23) protein and mRNA within the carotid atherosclerotic plaque remains elusive. Thus, we investigated herein, the association between plaque mRNA and protein expression of resistin and chemerin (and ChemR23) and carotid plaque instability in humans, and whether sex differences exist in the relationship between these adipokines and plaque instability. Methods: Human carotid plaques were processed for immunohistochemical/mRNA analysis of resistin, chemerin, and ChemR23. Plaque instability was assessed by gold-standard histological classifications. A semi-quantitative scoring system was used to determine the intensity of adipokine expression on macrophages/foam cells, as well as the percentage of inflammatory cells stained positive. Plaque adipokine protein expression was also digitally quantified and mRNA expression was assessed by qRT-PCR. Results: Resistin and chemerin mRNA expression was 80% and 32% lower, respectively, in unstable versus stable plaques ( P P P Conclusions: This study examined the relationship between resistin, chemerin, and ChemR23, and carotid plaque instability, with a specific analysis at the plaque level. We reported a positive association between plaque instability and protein levels of resistin, chemerin, and ChemR23 but a negative association with resistin and chemerin mRNA expression. This suggests these adipokines exert proinflammatory roles in the process of carotid atherosclerosis and may be regulated via a negative feedback regulatory mechanism.

Background: Chemerin has been newly defined to be released from mature adipocytes and the chemerin concentrations in human serum augmented with obesity. There is a subclinical chronic low-grade inflammatory response where insulin resistance (IR) may develop. The aim of this study is to expound the prospective role of chemerin the in inflammation. Also, investigate relation between chemerin and serum lipid, glucose, body fat percentage, and metabolic parameters in obese and lean women with IR. Lymphocytes and neutrophils play a major role in inflammation and comprise the first line of defense against infection. The ratio of absolute neutrophil count to lymphocyte count, the neutrophil-to-lymphocyte ratio (NLR), determined as is a novel inflammatory biomarker utilized as a prognostic factor in numerous diseases Methods: This study was designed to investigate serum chemerin, NLR, and high-sensitive C-reactive protein (hsCRP) levels in 50 obese women with IR and 50 lean healthy women. Results: Obese group had significant higher levels of serum chemerin, NLR, hsCRP levels and metabolic parameters than lean one. Chemerin also correlated positively with NLR inflammatory marker and body mass index (BMI). Neutrophil‐to‐lymphocyte ratio was related to pro‐inflammatory Conclusion: The present study elucidates that chemerin levels are concomitant with obesity and IR and could play a role in the inflammation, having key aspects of metabolic syndrome.

Objective: Gestational diabetes mellitus (GDM) is a medical complication of pregnancy. The aim of this study was to evaluate the correlations between the salivary and blood levels of oxidative stress markers and an adipokine chemerin, which play a role in the pathogenesis of GDM. Materials and methods: Study groups (Control (n = 29), GDM (n = 22)) had been assessed clinically healthy oral hygiene, according to the age range between 25 and 40 years, BMI

Background: Attempts have been made to recognize noninvasive markers for the identification of non-alcoholic fatty liver disease (NAFLD). Chemerin is a newly defined adipokine linked to insulin resistance and adipogenesis. Objective: This study intended to evaluate the diagnostic ability of serum chemerin compared with NAFLD fibrosis score as a noninvasive marker for the diagnosis and grading of NAFLD. Patients and methods: We enrolled 60 NAFLD patients and categorized them into 3 subgroups based on the fatty liver grade by ultrasound. Thirty healthy participants were recruited as a control group. ELISA method was used for serum chemerin levels measurement. Results: Serum chemerin levels were significantly higher in NAFLD cases than controls (p ≤ 0.001). Furthermore, these levels were positively correlated with the fatty liver grade (p ≤ 0.001). Serum chemerin was comparable to NAFLD fibrosis score as regards NAFLD diagnosis (p ≤ 0.001). Patients within the gray zone of NAFLD fibrosis score had a significantly higher serum chemerin levels in comparison to patients under the gray zone (p ≤ 0.001). Conclusion: Serum chemerin is a promising marker for diagnosing and grading of NAFLD. More research is required to determine its definitive clinical benefit in patients with NAFLD.

Background The homing capacity of human mesenchymal stem cells (hMSCs) to the injured sites enables systemic administration of hMSCs in clinical practice. In reality, only a small proportion of MSCs are detected in the target tissue, which is a major bottleneck for MSC-based therapies. We still don’t know the mechanism how MSCs are chemo-attracted to certain target organ and engrafted through trans-endothelial migration. In this study, we aimed to determine the mechanism how the circulating hMSCs home to the injured liver. Methods and results When we compare the cytokine array between normal and injured mouse liver at 1-day thioacetamide (TAA)-treatment, we found that chemerin, CXCL2, and CXCL10 were higher in the injured liver than normal one. Among three, only chemerin was the chemoattractant of hMSCs in 2D- and 3D-migration assay. Analysis of the signal transduction pathways in hMSCs showed that chemerin activated the phosphorylation of JNK1/2, ERK1/2 and p38, and finally upregulated CD44, ITGA4, and MMP-2 that are involved in the transendothelial migration and extravasation of MSCs. Upstream transcription regulators of CD44, ITGA4, and MMP-2 after chemerin treatment were MZF1, GATA3, STAT3, and STAT5A. To develop chemerin as a chemoattractant tool, we cloned gene encoding the active chemerin under the CMV promoter (CMV-aChemerin). We analyzed the migration of hMSCs in the 3D model for space of the Disse, which mimics transmigration of hMSCs in the liver. CMV-aChemerin-transfected hepatocytes were more effective to attract hMSC than control hepatocytes, leading to the enhanced transendothelial migration and homing of hMSCs to liver. The homing efficiency of the intravascularly-delivered hMSCs to liver was evaluated after systemic introduction of the CMV-aChemerin plasmid packed in liposome-vitamin A conjugates which target liver. CMV-aChemerin plasmid targeting liver significantly enhanced homing efficiency of hMSCs to liver compared with control plasmid vector. Conclusions Chemerin is the newly found chemoattractant of hMSCs and may be a useful tool to manipulate the homing of the intravascularly-administered hMSC to the specific target organ.

This study was undertaken to elucidate the effect of omega-3 and omega-6 supplementation on the levels of different adipokines and cytokines, as well as the antioxidant system, in relation to male reproductive hormones and testicular functions. Adult male Sprague-Dawley rats were daily gavaged with either physiological saline (control group), sunflower oil (omega 6 group; 1 mL/kg body weight), or fish oil (omega-3 group; 1000 mg/kg body weight) for 12 weeks. The administration of omega-3 or omega-6 resulted in decreased serum concentrations of kisspeptin 1, gonadotropin-releasing hormone, luteinizing hormone, follicle-stimulating hormone, and testosterone. In addition, it downregulated the mRNA expression levels of steroidogenic genes. The intratesticular levels of apelin, adiponectin, and irisin were elevated while chemerin, leptin, resistin, vaspin, and visfatin were declined following the administration of either omega-3 or omega-6. The testicular concentration of interleukin 10 was increased while interleukin 1 beta, interleukin 6, tumor necrosis factor α, and nuclear factor kappa B were decreased after consumption of omega-3 or omega-6. In the testes, the levels of superoxide dismutase, catalase, glutathione peroxidase 1, and the total antioxidant capacity were improved. In conclusion, the administration of omega-3 or omega-6 adversely affects the process of steroidogenesis but improves the antioxidant and anti-inflammatory status of the reproductive system via modulating the levels of testicular adipokines.

Metabolic syndrome includes the following symptoms: obesity, hyperlipidemia, hypertension, insulin resistance, and cardiovascular disease. The purpose of this review is to elucidate the role of adipokines in the regulation of the L-arginine-NO-synthas-NO signaling pathway in the pathogenesis of metabolic syndrome. The main questions raised in the review are: how adipokine secretion changes, how the level of their receptors is regulated, and which signaling pathways are involved in the transmission of adipokine signals when coupled to the L-arginine-NO-synthase-NO signaling cascade. Adipokines are peptide hormones that transmit a signal from adipose tissue to targets in the brain, blood vessels, liver, pancreas, muscles, and other tissues. Some adipokines have anti-inflammatory and insulin-sensitive effects: adiponectin, omentin, adipolin, chemerin, progranulin. Others have the negative inflammatory effect in the development ofmetabolic syndrome: visfatin, vaspin, apelin. Adipokines primarily regulate the expression and activity of endothelial NO-synthase. They either activate an enzyme involving 5-AMP protein kinase or Akt kinase, increasing its activity and synthesis of NO in the tissues of healthy patients: adiponectin, adipolin, omentin, or inhibit the activity of eNOS, which leads to a decrease in NO-synthase and suppression of mRNA bioavailability: vaspin, visfatin, apelin in metabolic syndrome, and a decrease in its activity leads to dissociation and endothelial dysfunction. It should be noted that the bioavailability of NO formed by NO-synthase is affected at many levels, including: the expression ofNO-synthase mRNA and its protein; the concentration of L-arginine; the level of cofactors of the reaction; and to detect the maximum activity of endothelial NO-synthase, dimerization of the enzyme is required, posttranslational modifications are important, in particular, phosphorylation of endothelial NO-synthase by serine 1177 with the participation of 5-AMP protein kinase, Akt kinase and other kinases. It should be noted that the participation of adiponectin, omentin, and kemerin in the regulation of the L-arginine-NO-synthase-NO cascade in metabolic syndrom opens up certain opportunities for the development of new approaches for the correction of disorders observed in this disease. The review analyzes the results of research searching in PubMed databases, starting from 2001 and up to 2020 using keywords and adipokine names, more than half of the references of the last 5 years.

Objectives This animal study aimed to demonstrate the synergistic effect of high-intensity interval training (HIIT) and alcoholic extract of nettle on serum chemerin and beta cells function in type 2 diabetic male rats. Methods Thirty-two STZ-induced diabetic male Wistar rats were randomly divided into four groups including the control group, the supplemented group with 200 mg/day of nettle, the training group with five sessions per week of HIIT, and the group with combined nettle and HITT intervention. Body weight, lipid profile, beta cells function, and chemerin level were assessed after eight weeks of the intervention. Results The values of chemerin significantly decreased in combined HIIT and nettle intervention group compared to the control group (p=0.001). The levels of glucose and insulin decreased significantly in nettle group, exercise group, and combined HIIT and nettle group (p=0.001). Conclusions The present study found that intense interval exercise with the consumption of alcoholic extract of nettle can affect the performance of beta cells, glucose, and insulin. Future human studies are warranted.

The exact role of adipokines in the pathogenesis of gestational diabetes mellitus (GDM) still remains not fully clear, and multiple studies have analyzed their potential contribution to the pathophysiology of this pregnancy complication. This study is aimed at evaluating serum chemerin, lipocalin 2, and apelin concentrations in GDM and healthy pregnant patients, assessing the correlation between these adipokines, and suggesting the potential role of these cytokines in the diagnosis and pathophysiology of GDM. The study comprised 237 pregnant women: 153 with GDM and 84 with physiological pregnancy. Serum concentrations of chemerin, lipocalin 2, and apelin were obtained at 24–29 weeks of gestation. The mean concentrations of chemerin and lipocalin 2 were significantly higher in the GDM group. The concentration of apelin was slightly higher in the GDM group, but not statistically significant. The strong positive correlation between chemerin and lipocalin 2 concentrations was noticed in both groups. Our data suggest that maternal chemerin and lipocalin 2 may play a significant role in the pathophysiology of GDM. We imply that these adipokines could potentially be established as novel biomarkers for the early identification of GDM. However, more studies are needed to analyze the effect of these adipokines on glucose metabolism during early pregnancy.

Obesity is associated with a series of health problems. Adipocytes are a huge repository of energy as well as an important source of many adipokines. In obesity, adipocytes are dysfunctional with excessive production and secretion of pro-inflammatory adipokines, such as tumor necrosis factor α (TNF-α), leptin, and chemerin. Recent studies have revealed that chemerin plays an important role in modulating physiologic as well as pathophysiologic processes. For example, chemerin stimulates maturation and differentiation of pre-adipocytes, acts as a chemoattractant and facilitates innate and acquired immunity. Furthermore, chemerin participates in the early stage of acute inflammation by reacting with the ChemR23 receptor. In various inflammatory diseases, the serum chemerin is significantly increased. Additionally, chemerin is also considered as an important biomarker for benign and malignant tumors. Thus, elucidating the pathologic mechanisms of chemerin action may facilitate the development of new therapeutic modalities to treat diverse inflammatory diseases. In this review, we summarize current knowledge of chemerin and its role as an important regulator in modulating various inflammatory diseases. Mechanisms underlying chemerin function in diverse diseases are explored to better understand its biochemistry and mechanisms of action.

Chemerin and resistin are two adipocytokines involved in inflammatory processes that may paly a role in the development of endometriosis. The purpose of the current study was to examine the levels of chemerin and resistin in the follicular fluid (FF) of endometriosis patients and additionally, assess the association of FF chemerin and resistin with the severity of endometriosis and the number of mature oocyte and embryos. A total of 80 reproductive-aged women who underwent intracytoplasmic sperm injection and embryo transfer were evaluated in this study. FF samples were obtained from subjects with (n = 40) and without endometriosis (n = 40). The concentrations of chemerin and resistin were examined using ELISA. The Resistin FF level was significantly (p-value=.03) higher in women with endometriosis than women without endometriosis, while the effect size was medium (d = 0.47). There was no significant difference in Chemerin concentration between the two groups of this study. Results also showed a tendency towards the increase of FF values of resistin and chemerin in endometriosis patients with stage III-IV than stage I-II; however, this difference was not significant. No significant correlations were found between FF levels of resistin and chemerin with the number of mature oocyte and embryos. Thus, elevated FF resistin levels may be associated with endometriosis.IMPACT STATEMENTWhat is already known on this subject? To our knowledge, no studies have investigated chemerin levels in follicular fluid of infertile women with endometriosis undergoing ICSI. Although follicular fluid levels of resistin have been previously studied in endometriosis, it has not been studied yet whether its level is associated with the number of oocyte and embryos.What do the results of this study add? Our results indicate that significantly increased resistin levels in follicular fluid may be associated with the presence of endometriosis.What are the implications of these findings for clinical practice and/or further research? The findings are promising in that significantly increased resistin levels may add to the knowledge of the pathophysiology of endometriosis.

Adipokines, especially chemerin, can interact with cytokines and other molecules in inflammation. To date, there is insufficient information regarding a possible correlation between functional disability and chemerin and other pro-inflammatory molecules in rheumatoid arthritis (RA). To identify the association of functional disability with serum chemerin and other pro-inflammatory molecules, including other adipokines, cytokines and E-selectin, in patients with RA. Cross-sectional study. Assessment: disease activity (DAS28-ESR) and functional disability (HAQ-DI). We compared the adipokines (chemerin, leptin, adiponectin, resistin, and visfatin), cytokines (TNF-α, IL-6, IL-1β, and IL-18) and E-selectin levels between RA with functional disability and RA non-disabled patients. Of 82 patients with RA, 43 (52%) had functional disability. The RA with functional disability group had higher chemerin (140 vs. 112 ng/mL, p = 0.007) than the non-disabled RA group. Chemerin correlated with the HAQ-DI (rho = 0.27, p = 0.02) and DAS28-ESR (rho = 0.21, p = 0.05). Severe activity correlated with IL-6 (rho = 0.33, p = 0.003) and E-selectin (rho = 0.23, p = 0.03) but not with disability. No other pro-inflammatory molecules correlated with HAQ-DI. High chemerin levels were associated with functional disability in RA, whereas no other molecules correlated with loss of function. These results encourage further studies assessing new roles of chemerin as a marker of impairment in RA.

Background: Elevated levels of chemerin can predict future ischemic cerebrovascular disease. Although chemerin is thought to play a role in atherosclerotic inflammation, whether circulating chemerin levels are associated with the severity of atherosclerosis remains to be determined. Objectives: Through the use of carotid Doppler ultrasonography, our aim in this study was to investigate the relationships of serum chemerin levels with carotid intima-media thickness (CIMT) as an indicator of generalized atherosclerosis. Methods: This study compared 40 patients with ischemic stroke and 40 healthy subjects. Measurements were made at end-diastole using color Doppler ultrasonography (CDUS) after a 5-min rest interval in a quiet and dark room. CIMT was defined as the distance between the innermost edge of the luminal echo to the innermost edge of the media/adventitia echo. CIMT was measured in the posterior wall of both common carotid arteries within 1 cm proximally to the bulbus. Three measurements were made on both sides and the average measurement was taken as the CIMT. Serum chemerin levels were determined in all patients and healthy subjects. Results: Serum chemerin levels were significantly higher in the patient group than in the control group (p=0.004). Serum chemerin levels were positively correlated with CIMT (p

Monocyte chemoattractant protein-1 (MCP-1) is the first discovered and most extensively studied chemotactic cytokines (CC = chemokine). Many studies on its role in the etiologies of obesity- and diabetes-related diseases have been increased exponentially during the past two decades. MCP-1, a chemokine involved in monocyte chemotaxis can be consistently found at high levels in the patients with type 2 diabetes mellitus. MCP1 may be an early predictor of complications of diabetes. Objective: Assessment of the levels of MCP-1 and other biochemical markers in diabetic subjects compared to a healthy group, which in turn can be beneficial to clarify the correlations of MCP-1 levels in diabetes mellitus with other clinical and biochemical parameters. Patients and methods: Eighty-one participants including both male and female, of cross-matched ages ranging between 30 – 60 years old were included in this study. They were divided into three equal groups: group I (control group), group II (recently diagnosed T2DM) and group III (old diagnosed T2DM more than 10 years). Results: The highest level of MCP-1 was found in the old diagnosed diabetic group while the lowest level was found in the non-diabetic control group. The LSD statistical analysis showed there was significant difference between all groups of the study. Our results showed that serum MCP-1 was elevated in cases of the group 3 (old diagnosed diabetic patients) who were suffering from diabetic nephropathy (9/27), diabetic retinopathy (9/27) and the last 9/27 were suffering of neuropathy. Conclusion: The MCP-1 level is increased in type 2 Diabetic patients and significantly increased with the progression of diabetes complications as diabetic retinopathy, diabetic nephropathy and diabetic neuropathy.

The antidepressant effect of eicosapentaenoic acid-derived bioactive lipid, resolvin E1 (RvE1), was examined in a murine model of chronic pain-induced depression using a tail suspension test. Because RvE1 reportedly possesses agonistic activity on a chemerin receptor ChemR23, we also examined the antidepressant effect of chemerin. Two weeks after surgery for unilateral spared nerve injury to prepare neuropathic pain model mice, immobility time was measured in a tail suspension test. Chronic pain significantly increased immobility time, and this depression-like behavior was attenuated by intracerebroventricular injection of RvE1 (1 ng) or chemerin (500 ng). These results demonstrate that RvE1 exerts an antidepressant effect in a murine model of chronic pain-induced depression, which is likely to be via ChemR23. RvE1 and its receptor may be promising targets to develop novel antidepressants.

The intrauterine environment and early-life nutrition are regulated by maternal biomarkers in the blood and breast milk. We aimed to explore epigenetic modifications that may contribute to differential chemerin expression in maternal plasma, colostrum, and breast milk and find its association with fetal cord blood and infant weight at 6 weeks postpartum. Thirty-three gestational diabetes mellitus (GDM) mothers and 33 normoglycemic mothers (NGT) were recruited. Two maternal blood samples (28th week of gestation and 6 weeks postpartum), cord blood, colostrum, and mature milk were collected. Methylation-specific polymerase chain reaction and enzyme-linked immunosorbent assay were conducted. The weight of the babies was measured at birth and 6 weeks postpartum. Serum chemerin levels at the 28th gestational week and 6 weeks postpartum were significantly lower for the NGT group as compared to the GDM group; (P < 0.05). Higher colostrum chemerin concentrations were observed in the GDM group and remained elevated in mature milk as compared to NGT (P < 0.05). Colostrum and breast milk chemerin levels showed an independent association with infant weight at 6 weeks postpartum (r = 0.270; P = 0.034) (r = 0.464; P < 0.001). Forty percent GDM mothers expressed unmethylated chemerin reflecting increased chemerin concentration in the maternal blood. This pattern was also observed in newborn cord blood where 52% of samples showed unmethylated chemerin in contrast to none in babies born to normoglycemic mothers. The results of this study highlight the critical importance of altered chemerin regulation in gestational diabetic mothers and its effect during early life period and suggest a possible role in contributing to childhood obesity.

Clear cell renal cell carcinoma (ccRCC) is characterized by accumulation of neutral lipids and adipogenic transdifferentiation. We assessed adipokine expression in ccRCC and found that tumor tissues and patient plasma exhibit obesity-dependent elevations of the adipokine chemerin. Attenuation of chemerin by several approaches led to significant reduction in lipid deposition and impairment of tumor cell growth in vitro and in vivo. A multi-omics approach revealed that chemerin suppresses fatty acid oxidation, preventing ferroptosis, and maintains fatty acid levels that activate hypoxia-inducible factor 2α expression. The lipid coenzyme Q and mitochondrial complex IV, whose biogeneses are lipid-dependent, were found to be decreased after chemerin inhibition, contributing to lipid reactive oxygen species production. Monoclonal antibody targeting chemerin led to reduced lipid storage and diminished tumor growth, demonstrating translational potential of chemerin inhibition. Collectively, the results suggest that obesity and tumor cells contribute to ccRCC through the expression of chemerin, which is indispensable in ccRCC biology. Significance: Identification of a hypoxia-inducible factor–dependent adipokine that prevents fatty acid oxidation and causes escape from ferroptosis highlights a critical metabolic dependency unique in the clear cell subtype of kidney cancer. Targeting lipid metabolism via inhibition of a soluble factor is a promising pharmacologic approach to expand therapeutic strategies for patients with ccRCC. See related commentary by Reznik et al., p. 1879. This article is highlighted in the In This Issue feature, p. 1861

Elevated serum concentrations of chemerin is a significant factor in the development of metabolic disorders.This systematic review and meta-analysis evaluated the influence of exercise training on serum concentrations of chemerin in patients with metabolic diseases.Thirteen studies including 463 participants were included and analysed using a random-effects model to calculate weighted mean differences with 95% confidence intervals.Results indicated that exercise training significantly decreased serum concentrations of chemerin in patients with metabolic diseases when compared with controls. Subgroup analysis showed that exercise training resulted in decreases in serum concentrations of chemerin in men, however, this was not significant in women. Moreover, subgroup analyses based on the type of exercise did not reveal differential effects on serum concentrations of chemerin.Exercise training may produce improvements in serum concentrations of chemerin in patients with metabolic diseases. Further longer-term studies are needed to confirm these findings.

WstępChemeryna jest hormonem wydzielanym przez adipocyty. W ostatnim czasie zwraca się uwagę na jej właściwości prozapalne i związane z karcynogenezą. Celem pracy było zbadanie stężeń chemeryny w surowicy i ślinie osób zdrowych oraz chorych z rakiem jelita grubego (RJG) w II i III stopniu zawansowania według klasyfikacji TNM (tumor, node, metastasis), a także ocena związku uzyskanych wartości z otyłością oraz wybranymi parametrami kliniczno-patologicznymi.Materiał i metodyDo badania zakwalifikowano 52 osoby, które podzielono na dwie równe grupy – kontrolną i badaną z nowotworem w II stopniu zaawansowania z cechą N0 oraz w III stopniu z cechą N+ według klasyfikacji TNM. Wewnątrz grup wyróżniono podgrupy osób o prawidłowej masie ciała (18,5 ≤ BMI < 25) oraz osoby otyłe i z nadwagą (BMI ≥ 25). Stężenia chemeryny w surowicy i ślinie oznaczano metodami immunoenzymatycznymi.WynikiMediany stężeń chemeryny były istotnie wyższe w grupie badanej w porównaniu z grupą kontrolną, zarówno w surowicy (384,36 ng/ml wobec 170,53 ng/ml), jak i ślinie (15,45 ng/ml wobec 4,57 ng/ml; p < 0,0001). W żadnej grupie w podgrupach z BMI powyżej i poniżej 25 nie znaleziono istotnych różnic w stężeniach badanej adipokininy. Nie odnotowano również istotnych różnic stężeń chemeryny w surowicy i ślinie między nowotworami w II i III stopniu zaawansowania TNM (p = 0,82 i p = 0,52).WnioskiOcena stężeń chemeryny w surowicy i ślinie u pacjentów z RJG sugeruje, że badana adipokina może być cennym biomarkerem wczesnej diagnostyki tego nowotworu. Wpływ BMI na uzyskane wyniki stężeń w surowicy i ślinie wydaje się nieistotny u chorych z RJG. Wydaje się, że w pewnych przypadkach łatwo akceptowane przez chorych badanie śliny może zastąpić badanie surowicy.

Objective This study aims to analyse the association of chemerin levels with several metabolic, biochemical and haematological parameters in a large Taiwanese population with relative healthy status. Design Cross-sectional study. Methods Data of 4101 healthy participants without history of hypertension, diabetes, dyslipidaemia and renal insufficiency from Taiwan Biobank were analysed. The demographic, biochemical and haematologic parameters were retrieved from the database. Chemerin levels were measured using commercially available enzyme-linked immunosorbent assay. Univariate and multivariate analysis was performed to test the independent correlates of chemerin. Results In the univariate analysis, circulating chemerin levels were positively associated with body mass index (BMI), waist circumference, waist-to-hip ratio (WHR), systolic (SBP) and diastolic blood pressure (DBP), haemoglobin A1C (HbA1C), total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), creatinine, uric acid, alanine aminotransferase (ALT), gamma-glutamyl transferase (γ-GT), leucocyte and platelet counts both in men and women and negatively associated with high-density lipoprotein cholesterol (HDL-C), estimated glomerular filtration rate (eGFR) and total bilirubin. In the multivariate analysis, BMI, HbA1C, triglyceride, uric acid, γ-GT and platelet counts predicted chemerin levels independently both in men and in women with positive correlation, while eGFR, total bilirubin and HDL-C predicted circulating chemerin levels independently with negative correlation. Conclusions Chemerin level is independently associated with multiple metabolic, biochemical and haematological parameters. This study provides further evidence on the molecular basis linking obesity with several human diseases.

To investigate the relationship of Children’s Dietary Inflammatory Index (C-DII™) scores with body fat distribution and serum adipokines in Brazilian schoolchildren. This population-based cross-sectional study enrolled 378 schoolchildren aged 8 and 9 years from Vicosa, Minas Gerais, Brazil. Food consumption was assessed using three 24-h dietary recalls from which C-DII scores were calculated. Serum adipokines [adiponectin, leptin, retinal-binding protein 4 (RBP4), and chemerin] were analyzed in blood samples. Sociodemographic characteristics and sedentary behavior were assessed using a semi-structured questionnaire. Total, truncal, android and gynoid body fat were evaluated by dual-energy X-ray absorptiometry (DXA). We compared the distributions of adiposity measures and serum adipokines by C-DII categories with linear regression, adjusting for potential confounders. The mean sample C-DII was 0.59 ± 0.94 and ranged from − 2.16 to + 2.75. The C-DII was not associated with central and total body fat. However, the C-DII was modestly inversely associated with adiponectin and RBP4, and modestly directly associated with chemerin. These results remained significant after adjusting for body fat. Every 1 SD of C-DII was related, respectively, to a − 0.8 (− 1.5, − 0.03) and to a − 0.1 (− 0.2, − 0.05) units lower mean of adiponectin and RBP4, and to 7.2 (0.3, 14.1) units higher of chemerin. Higher C-DII score was modestly inversely and directly associated with anti- and pro-inflammatory adipokines, respectively, in Brazilian children. The development of public health policies is needed to promote healthy eating habits during childhood to prevent the early onset of systemic inflammation and ill health effects later in life.

International audience; Adipokines are a large group of polypeptide hormones secreted by white adipose tissue able to interact through different receptors with several organs, including liver, central nervous system and gonads. In this review, we will focus on the adipokines that mediate their effects through G protein-coupled receptors, namely apelin and chemerin. Firstly, we will review their structure and that of their receptors (APJ for apelin, CMKLR1, GPR1 and CCRL2 for chemerin), as well as their tissue distribution and molecular mechanisms. In the second part of the review we will focus more in detail on the known metabolic and reproductive effects of these receptors, in both physiological and pathological conditions, underlining their relevant potential clinical implications.

Background The influence of serial changes of adipokines on maternal glucose metabolism from pregnancy to postpartum periods in women with previous gestational diabetes mellitus (pGDM) has not been thoroughly explored. We tried to examine the relationship between the serial changes of adipokines and the development of diabetes mellitus (DM) in women with pGDM. Methods We longitudinally measured following adipokines: high molecular weight (HMW) adiponectin, retinol-binding protein-4 (RBP-4), lipocalin-2, and chemerin, during pregnancy, and at 2 months and 3 years after delivery. Based on glucose status at postpartum 3 years, we divided into three groups: normal glucose tolerance (GDM-NGT, n=20), impaired glucose tolerance (GDM-IGT, n=23), and GDM-DM (n=22). We analyzed the correlations between adipokines and various metabolic parameters. Results Plasma HMW adiponectin levels were not different among the three groups during pregnancy. However, HMW adiponectin levels increased at 3 years after the delivery in women with GDM-NGT compared with women with GDM-DM. In the GDM-IGT group, HMW adiponectin levels increased at 2 months postpartum compared to pregnancy period. In contrast, HMW adiponectin levels showed no alternation after parturition in women with GDM-DM. HMW adiponectin was negatively correlated with body mass index and a homeostasis model assessment of insulin resistance. Other adipokines such as RBP-4, lipocalin-2, and chemerin neither showed any differences among the groups nor any significant correlations with 3 years postpartum status of glucose intolerance. Conclusion Serial changes of HMW adiponectin are associated with the maintenance of glucose metabolism in women with pGDM after delivery.

Metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD) are emerging threats in Pakistan. The prevalence of MetS is reported to be 18–46% in general population. Adipokines and their genetic polymorphisms are now considered as risk factors for these conditions. Chemerin modulates glucose and lipid homeostasis, nesfatin-1 acts as an anorexigenic peptide, desnutrin regulates adipose tissue fatty acid oxidation, adipocyte fat content, and size. Therefore, this study was designed to identify the molecular and genetic differences in the above-mentioned biomarkers in metabolic syndrome positive and negative individuals. This cross-sectional study was carried out at the Aga Khan University during October 2018 till August 2019. MetS positive (n = 92) versus negative (n = 208) adults aged between 18 and 50 years of age were recruited. MetS was diagnosed on the basis of National Cholesterol Education Program Adult Control Panel III criteria. Serum adipokine levels, lipid profile, blood glucose, and insulin were measured. Fatty liver was detected by ultra-sonographic scans. Chemerin rs17173608 polymorphism was determined by tetra-arm polymerase chain reaction. Higher chemerin (37.87 ± 13.60 vs. 24.03 ± 12.32 pg/ml), low desnutrin (103.08 ± 5.84;270.19 ± 25.67 pg/ml), and nesfatin levels (276.49 ± 31.09; 754.34 ± 57.77 pg/ml) were seen in Mets/NAFLD positive versus negative individuals, respectively. Serum chemerin showed a moderate positive correlation with MetS and fatty liver while desnutrin showed weak correlation with MetS, whereas nesfatin showed a moderate correlation with MetS and fatty liver (p < 0.05). Each unit increases in chemerin, and decrease in desnutrin was associated with higher odds of developing NAFLD (p < 0.05). The variant rs17173608 showed association with MetS phenotype (1.841 (1.101–3.078); p = 0.020). Presence of the minor “G” allele was seen to increase the risk of developing MetS by 1.567 (p < 0.012). High chemerin and low desnutrin are linked to fatty liver changes and MetS in a subset of local population. The presence of chemerin “G” allele increases the risk of developing MetS even further in the same individuals. Further studies are required for an in-depth analysis of the mechanism through which these biomarkers cause the effect.

Aims: Hemostasis and serum levels of adipokines in the body are affected by physical activity and overweight. The present study investigates the effect of the Pilates exercise program on serum levels of resistin, visfatin, and chemerin in overweight women Methods & Materials: In this quasi-experimental study, 28 women with overweight voluntarily participated and were randomly divided into two groups of exercise (n=14) and control (n=14). The Pilates exercise program was presented to the exercise group for 8 weeks, 3 sessions per week, while the control group performed no exercise. Blood samples were taken before the intervention and 48 hours after the intervention in a fasting state to measure the serum levels of resistin, visfatin, and chemerin. The t-test was used for intra-group comparison and ANCOVA for inter-group comparison of the variables. The obtained data were analyzed in SPSS v. 23, considering a significance level of P

Diabetes mellitus and obesity are very similar in terms of pathogenesis and pathophysiology. Most obese patients have adipose tissue dysfunction caused by genetic and environmental factors. Adipose tissue is the source of adipokines secreted from adipocytes. Vaspin, Visfatin and Chemerin are adipokines discovered in recent years. The study consists of 43 non-diabetic obese and 51 diabetic obese individuals. The PCR-RFLP method and agarose gel electrophoresis techniques were used to detect gene polymorphisms of Chemerin rs17173608, Vaspin rs2236242 and Visfatin rs2110385 from DNA samples. In our study, when diabetic obese and non-diabetic obese patient groups were examined in terms of Vaspin gene polymorphism, statistically significant results were obtained (22% → 7%, p=0.048, respectively). The distribution of Chemerin or Visfatin gene variants were not different in study groups (p>0.05). Our results indicate that Chemerin rs17173608 and Visfatin rs2110385 gene polymorphisms were not risk factors for development of diabetes in obese individuals, however, Vaspin rs2236242 gene polymorphism may be a contributory risk of development of diabetes in obese individuals.

Polycystic ovary syndrome (PCOS) involves abnormalities in ovarian, reproductive, and metabolic systems. Genetic polymorphisms associated with individual differences and variations might be related to complex disorders with unknown causes, including PCOS. Several leading genetic markers with known cellular functions have been identified among Iranian women presenting with PCOS. In particular, the existing evidence shows a significant relationship between PCOS and the following genetic polymorphisms: rs2275913 (interleukin-17A), rs9927163 (interleukin-32), Pro12Ala (peroxisome proliferator-activated receptor-γ), rs17173608 (chemerin), rs2236242 (vaspin), ApaI (vitamin D receptor), and rs7895833 (sirtuin 1). In addition, a higher risk of PCOS is associated with the rs2910164 (microRNA 146a), rs2241766 (adiponectin), -34 T/C (cytochrome 17), and rs1800682 (Fas) polymorphisms. Furthermore, protective effects against PCOS have been reported for the A4223C polymorphism of adenosine deaminase 1. Overall, the available data indicate that Iranian women with PCOS have a higher prevalence of polymorphisms in inflammation- and metabolism-related genes, but not in insulin-related genes. More extensive studies are needed to identify the ethnicity-related genetic associations in PCOS.

This trial evaluated the effects of thylakoid-rich spinach extract supplementation combined with a hypocaloric diet on body composition and serum levels of neopterin, chemerin, and omentin-1 in obese women with polycystic ovary syndrome (PCOS). In this randomized controlled trial, 48 obese women with PCOS, aged 20-45 years old, were recruited and randomly divided into thylakoid (n = 24) and placebo (n = 24) groups. They received a low-calorie diet with 5 g/day thylakoid-rich spinach extract or a low-calorie diet with 5 g/day placebo for 12 weeks. The mean age of the participants of the thylakoid group was 31.86 years, and the placebo group was 32.04 years. Thylakoid-rich spinach extract supplementation with a low-calorie diet increased serum levels of omentin-1 (10.90 vs. 3.87 ng/L; p < .001) and decreased fat mass (-5.19 vs. -1.35 kg; p < .001) and serum levels of neopterin (-0.66 vs. -0.38 nmol/L; p = .003) and chemerin (-41.24 vs. -11.26 ng/L; p < .001) in the thylakoid group compared to the placebo group. A significant improvement in omentin-1, chemerin, and neopterin by thylakoid-rich spinach extract supplementation was under the influence of weight change and insulin resistance status throughout the study. A significant decrease in the other anthropometric indices and insulin resistance was also observed in the thylakoid group, compared to the placebo group (p < .001, for all parameters). Thylakoid-rich spinach extract combined with a low-calorie diet increased circulating omentin-1 and decreased fat mass, abdominal obesity, as well as circulating chemerin, neopterin, and insulin in obese women with PCOS.

BACKGROUND Periodontitis and orthodontic treatment can lead to inflammatory root resorption (IRR) through an unclear mechanism. Chemerin, a novel chemoattractant protein, is closely associated with inflammation, affects osteoblast and osteoclast differentiation, and may play a role in IRR. We aimed to explore possible roles of the chemerin/ChemR23 interaction in cementoblast function and IRR and reveal a new IRR therapeutic target. METHODS Cementoblast function-related gene and protein expression in the immortalized murine cementoblast cell line OCCM-30 after treatment with chemerin and siChemR23 was examined by qRT-PCR and Western blotting. The roles of the MAPK and PI3K-Akt signaling pathways were studied using specific inhibitors. Cementoblast cytokine production under different treatment conditions was measured by enzyme-linked immunosorbent assay and qRT-PCR. Additionally, we modeled IRR in wild-type and chemerin-overexpressing mice and injected transgenic mice with anti-ChemR23 antibody to block ChemR23. We then calculated the root resorption volume and examined periodontal tissue cathepsin K, Runx2, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) expression. RESULT Chemerin suppressed cementoblast differentiation and mineralization and exerted a proinflammatory effect on cementoblasts. These effects were partially reversed by siChemR23 and reversed to different extents by p38, Erk1/2 and PI3K-Akt pathway inhibition, suggesting p38, Erk1/2 and PI3K-Akt pathways as signaling pathways downstream of chemerin/ChemR23. In vivo, chemerin overexpression worsened IRR. Moreover, chemerin expression was positively correlated with TNF-α, IL-6, and cathepsin K expression and negatively correlated with Runx2 expression. ChemR23 downregulation reversed these effects. CONCLUSION Chemerin/ChemR23 induced TNF-α and IL-6 expression dependent on Erk1/2, p38 MAPK, and PI3K-Akt signaling pathway activation, thereby regulating cementoblast function and affecting IRR.

Targeted proteomics has advantages over earlier conventional technologies for protein detection. We developed and validated an LC/MRM-MS-based targeted proteomic method combined with immunoaffinity precipitation for the enrichment and detection of low abundance chemerin isoforms in human biofluids. After tryptic digestion, each chemerin isoform was characterized by isoform-specific peptides, and the absolute quantification was achieved by using stable isotope-labeled peptides as internal standards. In serum, follicular fluid and synovial fluid, a total of 6 chemerin isoforms were identified and quantified, among which a novel natural isoform 153Q was discovered for the first time. The relative content of the six chemerin isoforms in human serum was 157S ≫ 156F ≫ 158K > 154F ≥ 155A > 153Q in the ratio of 25:17:5:2.5:2.2:1, respectively. The absolute contents were in the range of 88–3.5 ng/mL. This distribution remained consistent among the 3 biofluids analyzed. Total chemerin were found to be increased in both polycystic ovary syndrome (serum and follicular fluid) and rheumatoid arthritis (serum) patients. However, chemerin isoform analysis revealed that only 156F & 157S were increased in the former, while 155A, 156F & 157S were increased in the latter. This demonstrates the potential of this method in detailed characterization of changes in chemerin isoforms that may be of clinical relevance.

Background Chemerin a novel adipokine is linked to insulin resistance and adiposity which are major characteristics of polycystic ovary syndrome (PCOS). Results Chemerin level was found to be significantly higher in PCOS group than in control group (94.99 ± 12.52 ng/dl vs 73.41 ± 6.95 ng/dl) (P < 0.001) being the highest in obese PCO group, also chemerin positively correlated with BMI, fasting insulin, and HOMA-IR (P < 0.001), Multivariate linear regression analysis for factors affecting chemerin level in both PCO groups showed that the most important factor was fasting insulin (P = 0.042). Conclusion Chemerin correlates with insulin resistance and may be involved in the pathogenesis of insulin resistance in PCOS patients.

Background and aim Adipokines and hepatokines are proteins secreted by adipose tissue and the liver. To date, the levels of adipokines and hepatokines in cholelithiasis have only been evaluated in studies in adult patients. The purpose of our research was to assess the levels of circulating adipokines: chemerin, vaspin, progranulin, retinol-binding protein 4 (RBP-4) and hepatokine: fibroblast growth factor 21 (FGF-21) and to compare their concentrations in paediatric patients with and without cholelithiasis. Methods The prospective study included 54 children and adolescents diagnosed with gallstones and 26 controls. Fasting serum levels of adipokines and hepatokine were determined by enzyme-linked immunosorbent assays. Results The serum levels of chemerin, FGF-21 and RBP-4 were significantly higher in children and adolescents with gallstones compared to the control group. Elevated levels of triglycerides, RBP-4, and a homeostatic model for assessing insulin resistance (HOMA-IR) were observed in overweight or obese patients compared to patients with normal weight and cholelithiasis. Chemerin concentrations were increased in the normal-weight children and adolescents with cholelithiasis compared to the control group. Children and adolescents with gallstones and abnormal weight had significantly higher levels of chemerin, FGF-21 and RBP-4 than healthy controls. Conclusion Elevated serum chemerin levels were significantly higher in non-obese patients with cholelithiasis than in non-obese controls, suggesting a potential role of chemerin in the development of cholelithiasis in children and adolescents.