Chemerin Research Articles

Chicken chemerin alone or in mixture with adiponectin-visfatin impairs progesterone secretion by primary hen granulosa cells

Adipokines including adiponectin (ADIPO), chemerin (CHEM) and visfatin (VISF) are involved in metabolism and reproductive functions. These three adipokines are present in ovarian cells in different preovulatory follicles in hens. We have previously shown that VISF and ADIPO are able to modulate in vitro steroid production by hen granulosa cells (GCs). It is, however, unclear whether CHEM acts on hen ovarian cells. In addition, no study has yet investigated the effect of a mixture of several adipokines such ADIPO, VISF and CHEM on GCs from different preovulatory follicles. In this study, we investigated the effect of CHEM alone and in combination with ADIPO and VISF on cell viability, proliferation and progesterone secretion in cultured granulosa cells (GCs) from the largest follicles F1 and smaller ones (F3/F4) in the presence of gonadotropins (oLH and oFSH) or hIGF-1. First, various concentrations of chemerin were examined (0, 12, 25, 50 and 100 ng/mL) and then we determined the response to CHEM (at 25 ng/mL) in combination with ADIPO (10 µg/mL) and VISF (100 ng/mL). Chemerin exposure did not affect F1 and F3/F4 granulosa cell viability and proliferation whatever the concentation and in the presence of the mixture. However, it reduced progesterone secretion in dose dependent manner in both F1 and F3/F4 follicles. Furthermore, this CHEM inhibitory effect was significantly higher when CHEM was combined with ADIPO and VISF. Furthermore, CHEM reduced significantly oLH and oFSH- induced progesterone secretion in F1 GCs and oFSH and hIGF-1-induced progesterone secretion in F3/F4 GCs. Interestingly, this inhibitory effect of CHEM was similar in F1 GCs when CHEM was in mixture with ADIPO and VISF whereas it was significantly higher in F3/F4 GCs. Taken together, CHEM impairs progesterone secretion in cultured hen GCs and this inhibitory effect can be potentiated when it is in combination with other adipokines.

Chronic noise exposure induces Alzheimer's disease-like neuropathology and cognitive impairment via ferroptosis in rat hippocampus.

Chronic noise exposure poses a remarkable public health concern, drawing attention to its impacts on the brain. Ferroptosis is involved in several brain-related diseases. However, the role of ferroptosis in the effects of chronic noise on the brain remains elusive. This study aimed to investigate the effects of chronic noise exposure on the brain and elucidate the underlying mechanisms. A chronic noise-induced cognitive impairment model in rats was constructed and validated. The pathological state and ferroptosis level of the rat hippocampus were determined using Western blotting and immunohistochemistry. Bioinformatics was employed to investigate the interrelationship between chronic noise exposure and genes. Genetic relationships were analyzed using Mendelian randomization (MR) analysis. Cytoscape was employed for the prediction of upstream molecular and drug targets. In vivo experiments revealed that chronic noise exposure could induce Alzheimer's disease (AD)-like neuropathological changes in rat hippocampus and cognitive impairment. Moreover, protein markers indicative of ferroptosis and levels of lipid peroxidation were quantified to elucidate underlying mechanisms. Thereafter, oxidative stress- and ferroptosis-related differentially expressed genes (DEGs) underwent functional enrichment and PPI network analyses. Additionally, 8 genes with diagnostic significance were identified. In MR analysis, retinoic acid receptor responder 2 (Rarres2) gene exhibited a negative genetic relationship with AD. Chronic noise exposure could induce AD-like neuropathological changes and cognitive impairment via ferroptosis. The results of MR analysis indicated that Rarres2 gene may act as a protective factor in AD. This gene may be upstream of ferroptosis and serve as a target for the prevention and treatment of chronic noise-induced cognitive impairment.

Evaluation of salivary Chemerin in oral leukoplakia, oral squamous cell carcinoma and healthy controls

Introduction: Chemerin is a multifunctional chemoattractant cytokine, encoded by RARRES2 gene. Its role in oral carcinogenesis is largely unexplored. Study was undertaken to evaluate the role of salivary chemerin as a potential biomarker in the early diagnosis of oral cancer and to elucidate the clinicopathologic and prognostic significance of chemerin in different grades of Oral Squamous Cell Carcinoma (OSCC) and oral leukoplakia. Materials and Methods: The study comprised 96 subjects, divided into 3 groups, each consisting of 32 subjects. These groups were clinically and histopathologically diagnosed with OSCC, oral leukoplakia, and healthy controls, respectively. The whole unstimulated saliva (1.5 mL) was collected from the subjects using passive drool technique and immediately centrifuged at 3000 rpm for 10 minutes. The salivary chemerin level was estimated using the competitive sandwich enzyme-linked immunosorbent assay method. The statistical analysis was performed using R software EZR version 1.32. Independent t-tests, analysis of variance tests, and Scheffe Multiple Comparisons were carried out to compare quantitative parameters. A receiver operating characteristic (ROC) curve was plotted to assess diagnostic accuracy of salivary chemerin. Results: Significantly higher levels of salivary chemerin were observed in OSCC and oral leukoplakia patients compared to healthy controls (P < 0.05). The study further established an increase in salivary chemerin concentration in different histological grades of OSCC and oral leukoplakia. ROC curve analysis suggested that salivary chemerin is a highly sensitive and specific indicator for early screening and detection of oral leukoplakia and OSCC. Conclusion: Salivary chemerin can be considered as a reliable and specific indicator for the early screening and detection of oral leukoplakia and OSCC and a highly sensitive biomarker which may aid in detection of malignant transformation of oral leukoplakia.

Circulating Chemerin Is Elevated in Women With Preeclampsia.

Preeclampsia is a severe complication of pregnancy. Chemerin is an adipokine secreted from adipose tissue and highly expressed in placenta. This study evaluated the biomarker potential of circulating chemerin to predict preeclampsia. Maternal plasma and placenta were collected from women with early-onset preeclampsia (<34 weeks), with preeclampsia and eclampsia, or before preeclampsia diagnosis (36 weeks). Human trophoblast stem cells were differentiated into syncytiotrophoblast or extravillous trophoblasts across 96 hours. Cells were cultured in 1% O2 (hypoxia) or 5% O2 (normoxia). Chemerin was measured by enzyme-linked immunosorbent assay (ELISA) and RARRES2 (gene coding chemerin) by reverse transcription-quantitative polymerase chain reaction. Circulating chemerin was increased in 46 women with early-onset preeclampsia (<34 weeks) compared to 17 controls (P < .0006). Chemerin was increased in placenta from 43 women with early-onset preeclampsia compared to 24 controls (P < .0001). RARRES2 was reduced in placenta from 43 women with early-onset preeclampsia vs 24 controls (P < .0001). Chemerin was increased in plasma from 26 women with established preeclampsia (P = .006), vs 15 controls. Circulating chemerin was increased in 23 women who later developed preeclampsia vs 182 who did not (P = 3.23 × 10-6). RARRES2 was reduced in syncytiotrophoblast (P = .005) or extravillous trophoblasts (P < .0001). Hypoxia increased RARRES2 expression in syncytiotrophoblast (P = .01) but not cytotrophoblast cells. Circulating chemerin was elevated in women with early-onset preeclampsia, established preeclampsia, and preceding preeclampsia diagnosis of preeclampsia. RARRES2 was dysregulated in placenta complicated by preeclampsia and may be regulated through hypoxia. Chemerin may have potential as a biomarker for preeclampsia but would need to be combined with other biomarkers.

Chemerin and Chemokine-like Receptor 1 Expression in Ovarian Cancer Associates with Proteins Involved in Estrogen Signaling

Chemerin, a pleiotropic adipokine coded by the RARRES2 gene, has been reported to affect the pathophysiology of various cancer entities. To further approach the role of this adipokine in ovarian cancer (OC), intratumoral protein levels of chemerin and its receptor chemokine-like receptor 1 (CMKLR1) were examined by immunohistochemistry analyzing tissue microarrays with tumor samples from 208 OC patients. Since chemerin has been reported to affect the female reproductive system, associations with proteins involved in steroid hormone signaling were analyzed. Additionally, correlations with ovarian cancer markers, cancer-related proteins, and survival of OC patients were examined. A positive correlation of chemerin and CMKLR1 protein levels in OC (Spearman's rho = 0.6, p < 0.0001) was observed. Chemerin staining intensity was strongly associated with the expression of progesterone receptor (PR) (Spearman´s rho = 0.79, p < 0.0001). Both chemerin and CMKLR1 proteins positively correlated with estrogen receptor β (ERβ) and estrogen-related receptors. Neither chemerin nor the CMKLR1 protein level was associated with the survival of OC patients. At the mRNA level, in silico analysis revealed low RARRES2 and high CMKLR1 expression associated with longer overall survival. The results of our correlation analyses suggested the previously reported interaction of chemerin and estrogen signaling to be present in OC tissue. Further studies are needed to elucidate to which extent this interaction might affect OC development and progression.

The role of Chemerin in human diseases.

Chemerin is a protein encoded by the Rarres2 gene that acts through endocrine or paracrine regulation. Chemerin can bind to its receptor, regulate insulin sensitivity and adipocyte differentiation, and thus affect glucose and lipid metabolism. There is growing evidence that it also plays an important role in diseases such as inflammation and cancer. Chemerin has been shown to play a role in the pathogenesis of inflammatory and metabolic diseases caused by leukocyte chemoattractants in a variety of organs, but its biological function remains controversial. In conclusion, the exciting findings collected over the past few years clearly indicate that targeting Chemerin signaling as a biological target will be a major research goal in the future. This article reviews the pathophysiological roles of Chemerin in various systems and diseases,and expect to provide a rationale for its role as a clinical therapeutic target.

The effect of oestradiol and progesterone on chemerin system expression in the porcine endometrium during early pregnancy and the mid-luteal phase of the oestrous cycle

Chemerin is an adipokine which is the product of the RARRES2 gene expressed mainly in adipose tissue. This hormone exerts biological effects via three metabotropic receptors: chemokine like receptor 1 (CMKLR1), G protein-coupled receptor 1 (GPR1), and C–C chemokine receptor-like 2 (CCRL2). Chemerin exerts pleiotropic effects and participates in the regulation of many processes, such as blood pressure control, immune system regulation, inflammation, and angiogenesis. There is a growing body of evidence to indicate that chemerin is involved in the regulation of reproductive system functions. However, little is known about the regulation of chemerin system (chemerin and its receptors) expression. The authors hypothesized that steroid hormones affect the expression of the chemerin system in the uterus of domestic pigs. Thus, the aim of this study was to investigate the influence of steroids, oestradiol (E2), and progesterone (P4), on the gene (qPCR) and protein (Western blot) expression of chemerin receptors, RARRES2 gene expression as well as chemerin secretion (ELISA) by endometrial slices during early pregnancy (days 10 to 11, 12 to 13, 15 to 16, and 27 to 28) and the mid-luteal phase of the oestrous cycle (days 10 to 11). Both steroid hormones modulated the expression of chemerin receptor genes and proteins, as well as the abundance of RARRES2 mRNA transcripts. The study also demonstrated that E2 increased chemerin protein secretion by endometrial cells during the maternal recognition of pregnancy (days 12 to 13) and decreased its release during embryo implantation (days 15 to 16). P4 had no significant effect on chemerin levels during the studied periods of gestation and the oestrous cycle. These observations suggest that the effects of E2 and P4 on the chemerin system are dependent on the period of gestation or the oestrous cycle. Our results support the hypothesis that the hormonal environment could modulate the expression of the chemerin system in the endometrium.

Chemerin Forms: Their Generation and Activity.

Chemerin is the product of the RARRES2 gene which is secreted as a precursor of 143 amino acids. That precursor is inactive, but proteases from the coagulation and fibrinolytic cascades, as well as from inflammatory reactions, process the C-terminus of chemerin to first activate it and then subsequently inactivate it. Chemerin can signal via two G protein-coupled receptors, chem1 and chem2, as well as be bound to a third non-signaling receptor, CCRL2. Chemerin is produced by the liver and secreted into the circulation as a precursor, but it is also expressed in some tissues where it can be activated locally. This review discusses the specific tissue expression of the components of the chemerin system, and the role of different proteases in regulating the activation and inactivation of chemerin. Methods of identifying and determining the levels of different chemerin forms in both mass and activity assays are reviewed. The levels of chemerin in circulation are correlated with certain disease conditions, such as patients with obesity or diabetes, leading to the possibility of using chemerin as a biomarker.

Chemerin Effect on the Endometrial Proteome of the Domestic Pig during Implantation Obtained by LC-MS/MS Analysis.

Chemerin (CHEM) is a hormone mainly expressed in adipocytes involved in the regulation of energy homeostasis and inflammatory response. CHEM expression has been demonstrated in the structures of the porcine hypothalamic-pituitary-gonadal axis, as well as in the uterus, trophoblasts and conceptuses of pigs. In this study, we performed high-throughput proteomic analyses (liquid chromatography with tandem mass spectrometry, LC-MS/MS) to examine the influence of CHEM (400 ng/mL) on differentially regulated proteins (DRPs) in the porcine endometrial tissue explants during implantation (15 to 16 days of gestation). Among all 352 DRPs, 164 were up-regulated and 188 were down-regulated in CHEM-treated group. DRPs were assigned to 47 gene ontology (GO) terms (p-adjusted < 0.05). Validation of four DRPs (IFIT5, TGFβ1, ACO1 and PGRMC1) by Western blot analysis confirmed the veracity and accuracy of the LC-MS/MS method used in the present study. We suggest that CHEM, by modulating various protein expressions, takes part in the endometrial cell proliferation, migration and invasion at the time of implantation. It also regulates the endometrial immune response, sensitivity to P4 and the formation of new blood vessels. Additionally, CHEM appears to be an important factor involved in endothelial cell dysfunction during the pathogenesis of preeclampsia. The identification of a large number of DRPs under the influence of CHEM provides a valuable resource for understanding the molecular mechanisms of this hormone action during implantation, which is a prerequisite for better control of pig reproduction.

Chemerin effect on transcriptome of the porcine endometrium during implantation determined by RNA-sequencing†.

It is well known that the body's metabolism and reproduction are closely related. Chemerin (CHEM) is one of many biologically active proteins secreted by the adipose tissue involved in the regulation of the energy homeostasis of the organism. In the present study, RNA-sequencing was performed to investigate the differentially expressed genes (DEGs), long non-coding RNAs (lncRNAs), and alternatively spliced (AS) transcripts in the cultured porcine endometrium exposed to chemerin for 24hours (CHEM; 400ng/mL) collected during the implantation period (15-16days of gestation). High-throughput sequencing of transcriptomes was performed on the Illumina NovaSeq 6000 platform (Illumina, USA). In the current study, among all 130 DEGs, 58 were upregulated and 72 were downregulated in the CHEM-treated group. DEGs were assigned to 73 functional annotations. Twelve identified lncRNAs indicated a difference in the expression profile after CHEM administration. Additionally, we detected 386 differentially AS events encompassed 274 protein-coding genes and 2 lncRNAs. All AS events were divided into five alternative splicing types: alternative 3' splice site (A3SS), 5' splice site (A5SS), mutually exclusive exons (MXE), retention intron (RI), and skipping exon (SE). Within all AS events, we identified 42 A3SS, 43 A5SS, 53 MXE, 9 RI, and 239 SE. In summary, CHEM affects the transcriptomic profile of the porcine endometrium, controlling the expression of numerous genes, including those involved in the cell migration and adhesion, angiogenesis, inflammation, and steroidogenesis. It can be assumed that CHEM may be an important factor for a proper course of gestation and embryo development.

The Association of Serum Circulating Neuropeptide Q and Chemerin Levels with Cardiometabolic Risk Factors among Patients with Metabolic Syndrome

The potential involvement of neuropeptide Q (NPQ) and chemerin (CHEM) in metabolic disorders is yet to be fully elucidated. The aim of this study was to evaluate serum concentrations of NPQ and CHEM and to establish their relationship with cardiometabolic risk factors among individuals with metabolic syndrome. A total of 66 patients with metabolic syndrome (MetS) and 83 healthy volunteers (non-MetS) underwent biochemical, blood pressure, and anthropometric measurements. The concentration of NPQ in the MetS group was significantly lower (0.47 (0.34 ; 0.54) vs. 0.52 (0.43 ; 0.60) ng/mL, p = 0.015) than in non-MetS, while there were no differences in CHEM level. In the entire study population, we observed several negative correlations between NPQ concentration and waist-hip ratio (WHR), visceral adipose tissue, diastolic blood pressure (DBP), triglycerides (TG) along with a positive correlation with high-density lipoprotein (HDL), total muscle mass, and CHEM. Moreover, a negative correlation was observed in the MetS group between NPQ and glycemia. CHEM showed no significant correlations with cardiometabolic risk factors in the study population. In a multiple regression model, the total muscle mass proved to be an independent factor determining NPQ concentration in the population (p < 0.00000001, R2adj = 28.6%). NPQ seems to protect against metabolic disorders correlated with obesity. Thus, it is worth considering NPQ level as a candidate protective biomarker of metabolic syndrome complications.

Adipokine, gut and thyroid hormone responses to probiotic application in chukar partridges (Alectoris chukar) exposed to heat stress.

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.

Genetic parameters and weighted single-step genome-wide association study for supernumerary teats in Holstein cattle

Supernumerary teats (SNT) are a common epidermal abnormality of udders in mammals. The SNT negatively affect machine milking ability, udder health, and animal welfare and sometimes act as reservoirs for undesirable bacteria, resulting in economic losses on calves and lactating cows due to the cost of SNT removal surgery, early culling, and low milk yield. This study aimed to analyze the incidence and genetic parameter of SNT and detect SNT-related genes in Chinese Holstein cattle. In this study, the incidence of SNT was recorded in 4,670 Chinese Holstein cattle (born between 2008 and 2017) from 2 farms, including 734 genotyped cows with 114,485 SNPs. The SNT had a total frequency of 9.8% and estimated heritability of 0.22 (SE = 0.07), which were obtained using a threshold model in the studied Chinese Holstein population. Furthermore, we calculated approximate genetic correlations between SNT and the following indicator traits: 12 milk production, 28 body conformation, 5 fertility and reproduction, 5 health, and 9 longevity. Generally, the estimated correlations, such as 305-d milk yield for third parity (-0.55; SE = 0.02) and age at first calving in heifer (0.19; SE = 0.03), were low to moderate. A single-step GWAS was implemented, and 10 genes associated with SNT located in BTA4 were identified. The region (112.70-112.90 Mb) on BTA4 showed the highest genetic variance for SNT. The quantitative trait loci on BTA4 was mapped into the RARRES2 gene, which was previously shown to affect adipogenesis and hormone secretion. The WIF1 gene, which was located in BTA5, was also considered as a candidate gene for SNT. Overall, these findings provide useful information for breeders who are interested in reducing SNT.

The Comparison of Predictive Value Among Chemerin, IL-18 and Hormonal Parameters in Assessing the Risk of Metabolic Syndrome in Men.

Chemerin (CHEM) is a new proinflammatory adipokine involved in the immune, metabolic and reproductive processes. Low–grade state inflammation (LGSI) is a key element in the pathogenesis of metabolic syndrome (MS). Low SHBG is a good marker of male hypogonadism in MS. This study evaluated the prognostic value of selected adipokine, LGSI, and androgenic parameters in predicting the risk of MS among men. One hundred thirty-two random men aged 40 to 70 years old were enrolled. Measurements of anthropometric indices, blood pressure, and laboratory tests were carried out. A total of 62 men (47%) were diagnosed with MS. Chemerin concentrations were higher in men diagnosed with MS compared to healthy: 89.48 (78.12–112.10) vs. 77.9 (65.12–98.64) ng/mL; p = .002. Men diagnosed with MS presented with lower levels of total testosterone: 5.75 (4.00–6.57) vs. 6.40 (5.50–8.40) ng/mL; p = .0014 and SHBG: 46.58 (35.13–66.28) vs. 71.97 (56.1–92.7) nM/L; p < 0.000001. Elevated LGSI indices were demonstrated in men with MS as opposed to healthy [IL–18: 530.64 (409.12–640.56) vs. 418.85 (348.14–496.44) pg/mL; p = .000033 and hs–CRP: 2.15 (0.97–4.26) vs. 1.01 (0.41–2.68) ng/mL; p = .0057)]. In multivariate regression analysis, the highest negative predictive value in assessing the risk of MS was SHBG serum concentration, while the highest positive predictive values were: IL-18, hypertriglyceridemia, and waist circumference. Decreased SHBG levels, combined with elevated IL-18 concentrations in men showing hypertriglyceridemic waist phenotype, significantly increase the risk of MS.

Variants in the RARRES2 gene are associated with serum chemerin and increase the risk of diabetic kidney disease in type 2 diabetes

Genetic susceptibility plays an important role in the pathogenesis of diabetic kidney disease (DKD). Recent studies have suggested that chemerin (encoded by the RARRES2 gene) is a risk factor for the development of DKD. We investigate the relationship between RARRES2 single nucleotide polymorphisms (SNPs) and DKD and their correlation with serum chemerin levels in Chinese individuals with type 2 diabetes (T2D). A total of 256 individuals with T2D were enrolled in this case-control study and classified into normo-, micro- and macroalbuminuria groups according to their urinary albumin/creatinine ratio (UACR). All exons of the RARRES2 gene were sequenced by polymerase chain reaction-direct sequencing, and 7 SNPs were genotyped. We found that the minor alleles of rs1047207, rs1047575 and rs1047586 were significantly associated with macroalbuminuria. Carriers of the minor allele of rs1047575 and rs1047586 also had higher urinary albumin (U-Alb) and UACR levels under both homo- and heterozygotic conditions than carriers of the major allele under the homozygotic condition. The minor alleles of rs1047207, rs1047575 and rs1047586 were significantly associated with increased serum chemerin levels under the homozygotic condition. These SNPs in the RARRES2 gene probably affect chemerin expression and likely confer susceptibility to albuminuria in individuals with T2D.

Expression of Chemerin and Its Receptors in the Porcine Hypothalamus and Plasma Chemerin Levels during the Oestrous Cycle and Early Pregnancy.

Chemerin (CHEM) may act as an important link integrating energy homeostasis and reproductive functions of females, and its actions are mediated by three receptors: chemokine-like receptor 1 (CMKLR1), G protein-coupled receptor 1 (GPR1), and C-C motif chemokine receptor-like 2 (CCRL2). The aim of the current study was to compare the expression of CHEM and its receptor (CHEM system) mRNAs (quantitative real-time PCR) and proteins (Western blotting and fluorescent immunohistochemistry) in the selected areas of the porcine hypothalamus responsible for gonadotropin-releasing hormone production and secretion: the mediobasal hypothalamus, preoptic area and stalk median eminence during the oestrous cycle and early pregnancy. Moreover, plasma CHEM concentrations were determined using ELISA. The expression of CHEM system has been demonstrated in the porcine hypothalamus throughout the luteal phase and follicular phase of the oestrous cycle, and during early pregnancy from days 10 to 28. Plasma CHEM levels and concentrations of transcripts and proteins of CHEM system components in the hypothalamus fluctuated throughout pregnancy and the oestrous cycle. Our study was the first experiment to demonstrate the presence of CHEM system mRNAs and proteins in the porcine hypothalamus and the correlations between the expression levels and physiological hormonal milieu related to the oestrous cycle and early pregnancy.

Circulating Chemerin Levels, but not the RARRES2 Polymorphisms, Predict the Long-Term Outcome of Angiographically Confirmed Coronary Artery Disease.

Chemerin, a novel adipokine, has been associated with metabolic, inflammatory, and atherosclerotic diseases. We aimed to determine the genetic basis of chemerin levels by conducting a genome-wide association study (GWAS) and to investigate the role of RARRES2 polymorphisms and circulating chemerin levels in the long-term outcome of coronary artery disease (CAD). A total of 2197 participants from the Taiwan Biobank (TWB) were recruited for the GWAS analysis, and 481 patients with angiographically confirmed CAD were enrolled for long-term outcome analysis. One locus of genome-wide significance with a single independent association signal was identified in the GWAS for chemerin levels with the peak association at the RARRES2 gene promoter region polymorphism rs3735167 (p = 2.35 × 10−21). In the CAD population, borderline significance was noted between RARRES2 polymorphisms and chemerin levels, whereas high chemerin levels were associated with obesity, female sex, diabetes mellitus, hypertension, current smoking, high platelet and leukocyte counts, anemia, impaired renal function, high C-reactive protein (CRP) levels, and multi-vessel disease. Kaplan–Meier survival curves indicated that the patients with high chemerin and CRP levels, but not those with RARRES2 polymorphisms, had a lower survival rate and higher combined cerebral and cardiovascular event rates. Combined chemerin and CRP levels further revealed a stepwise increase in poor clinical outcomes from low- to high-risk subgroups. In conclusion, rs3735167 is the lead RARRES2 polymorphism for chemerin levels in Taiwanese. Chemerin levels, but not the rs3735167 genotypes, predicted the long-term outcome of CAD, especially when combined with CRP levels.

Serum chemerin and its association with coronary heart disease in diabetic and nondiabetic patients

Objective Chemerin is a novel adipokinine that is associated with inflammation and adipogenesis. Our aim was to study the relationship between serum chemerin and coronary artery disease (CAD) in angiographically documented participants and participants without CAD among patients with diabetes mellitus and those without diabetes mellitus. Background Chemerin is one of the adipokines that is linked to fat metabolism and thought to be linked to atherosclerosis and CAD. Patient and methods This cross-sectional study was conducted on 80 patients recruited from among patients presenting to the catheter laboratory of Sharq Al-Madina Hospital in Alexandria. Participants were divided into the following groups: group 1 included 20 diabetic patients with CAD; group 2 included 20 diabetic patients without CAD; group 3 included 20 nondiabetic patients with CAD; and group 4 included 20 participants as controls. Patients of groups 1 and 3 had angiographically documented CAD. Serum chemerin, glycemic control parameters (fasting blood sugar, glycated hemoglobin, fasting insulin, and homeostasis model assessment for insulin resistance), lipid profile, and urinary albumin–creatinine ratio were assessed. Results The results of the present study showed that there was a statistically significant increase in mean serum chemerin level in group 1 compared with groups 2 and 4 (P = 0.007and 0.001, respectively), as well as compared with group 3, but this increase was not statistically significant. There was also a statistically significant increase in serum chemerin in group 3 compared with groups 2 and 4 (P = 0.001 and 0.003, respectively). However, there was no statistically significant difference between the two CAD groups (groups 1 and 3) with regard to the Gensini score. There was no statistically significant correlation among the other studied parameters. Conclusion Serum chemerin level was increased in CAD patients, irrespective of whether they were diabetic or nondiabetic, but did not increase as the severity of CAD increased when assessed by the Gensini score.

Serum omentin-1 and chemerin concentrations in pancreatic cancer and chronic pancreatitis.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by very poor prognosis. It is caused by asymptomatic course of the disease at early stage. Symptomatic PDAC means usually advanced stage of the disease, making radical treatment impossible. Finding of biological PDAC marker could improve PDAC treatment through early diagnosis. In our study, we investigated two adipokines: omentin and chemerin concentration in PDAC, chronic pancreatitis (CP) and healthy individuals. We examined 27 PDAC patients, 10 CP patients and 36 controls. To determine concentration of adipokines we used ELISA immunoenzymatic assay. Level of both adipokines was increased when comparing control group to PDAC patients. Additionally, chemerin concentration in CP group was elevated comparing to control. To evaluate both adipokines as potential PDAC biomarkers we performed ROC analysis. Chemerin (AUC = 0.913) displayed better discriminant ability than omentin-1 (AUC = 0.73). Some authors believe that chemerin may promote tumour growth by stimulating angiogenesis and is supposed to be a factor recruiting mesenchymal stroma cells (MSC) in tumour regions. Omentin-1 can inhibit tumourigenesis by TP53 stimulation. On the other hand, according to some studies, omentin-1 may promote cancer proliferation via Akt signalling pathway. Results from our study showed significantly elevated level of chemerin and omentin-1 in PDAC patients. Therefore, we believe that both investigated adipokines may provide promising and novel pharmacological insights for oncological diagnosis in the near future.

Changes of Chemerin Production in Obese Patients with Different States of Carbohydrate Metabolism

Chemerin is an adipose tissue mediator involved in the regulation of many processes, including lipogenesis, inflammatory responses, etc. The role of chemerin in the development of insulin resistance still needs better understanding. The aim of the study was to investigate chemerin production in obese patients with different states of carbohydrate metabolism. The study included 155 patients with diagnosed obesity and 34 patients with overweight. The control group 1 consisted of 43 conditionally healthy donors without obesity. For comparison of the research data on evaluation of tissue-specific mRNA expression of the genes IL-6, TNF-α, RARRES2, (encoding IL-6, TNF-α, and chemerin, respectively) control group 2 consisting of 30 non-obese was also included into this study. The relative level of mRNA expression of the genes IL-6, TNF-α and RARRES2 (encoding IL-6, TNF-α and chemerin, respectively) was carried out using real time PCR. Concentrations of IL-6, TNF-α, and chemerin were measured in serum/plasma using an enzymelinked immunosorbent assay (ELISA). Significant differences were found in the plasma level of chemerin and tissue-specific patterns of RARRES2 gene expression in obese patients; these changes depended on the degree of obesity and the state of carbohydrate metabolism. Opposite associations between RARRES2 gene expression and expression TNF-α and IL-6 genes have been recognized in adipose tissues of different localization: in obese patients (BMI ≤ 40 kg/m2) without type 2 diabetes mellitus (DM2) they were negative, while in obese patients with DM2 diabetes they were positive. The recognized correlations between the plasma content of chemerin and the expression level of its gene in biopsies with various parameters of carbohydrate and lipid metabolism, and proinflammatory molecules indicate chemerin involvement in metabolic and immune processes in obesity.