Chemerin Research Articles

The chemerin production changes in obese patients with different carbohydrate metabolism state

Chemerin is a mediator of adipose tissue involved in the regulation of many processes, including lipogenesis, and inflammatory response. The role of chemerin in the development of insulin resistance has been insufficiently studied and needs detailed 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 a diagnosis of obesity; 34 patients with overweight. The control group 1 consisted of 43 conditionally healthy donors who did not have obesity. For comparison of the results of a study to determine the levels of tissue-specific mRNA expression of the genes IL-6, TNF-a, RARRES2, (encoding IL-6, TNF-a and chemerin) in adipose tissue introduced a control group 2 - 30 patients without obesity. Study on the relative level of mRNA expression of the genes IL-6, TNF-a and RARRES2 (encoding IL-6, TNF-a and chemerin) was carried out using real time PCR. Concentrations of IL-6, TNF-a, and chemerin were measured in serum/plasma using an enzyme-linked immunosorbent assay (ELISA). We found significant differences in the plasma level of chemerin and tissue-specific features of RARRES2 gene expression in obese patients, depending on the degree of obesity and the state of carbohydrate metabolism. Multidirectional associations of RARRES2 gene expression with TNF-a and IL-6 genes in adipose tissues of different localization are shown: in obese patients (BMI £40 kg/m2) without type 2 diabetes - negative, and type 2 diabetes - positive. Identified relationship chemerin plasma content and the expression level of its gene in biopsies with various parameters of carbohydrate and lipid metabolism, proinflammatory molecules indicate chemerin involved in metabolic and immune processes in obesity.

The expression and clinical significance of Chemerin in cervical intraepithelial neoplasia and cervical cancer

Objective To investigate the expression of Chemerin in cervical intraepithelial neoplasia(CIN) and cervical cancer and its relation with clinicopathological characteristics. Methods The expression of Chemerin was determined with enzyme-linked immunosorbent assay (ELISA) in 35 cervical cancer cases, 20 cervical intraepithelial neoplasia cases and 20 normal persons. The association of serum level of Chemerin with clinicopathological charactersistics was analyzed. Results The level of Chemerin was the highest in cervical cancer cases [(2113.35±198.64)ng/L], higher in CIN [(1562.78±158.65)ng/L], and low in normal persons [(946.36±113.57)ng/L], showing significant difference among three groups. The serum level of Chemerin in cervical cancer were positively correlated with Federation International of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis (P<0.05). Serum Chemerin levels were increased with clinical FIGO stage and showed significantly positive correlation with FIGO stage (rs=0.92, P=0.000). Conclusions The expression of Chemerin in patients with cervical carcinoma is increased. Chemerin may be used as reference indicator to predict its progression in cervical carcinoma. Key words: Adipokines/ME; Cervical intraepithelial neoplasia/ME; Uterine cervical neoplasms/ME

High plasma chemerin is associated with renal dysfunction and predictive for cardiovascular events — Insights from phenotype and genotype characterization

The novel adipokine chemerin, encoded by the RARRES2 gene, has been suggested to be linked to insulin resistance and to the metabolic syndrome (MetS). However, no well-defined cardiovascular profile has been reported and the association with coronary artery disease (CAD) is a matter of debate. Because there is a relation between renal dysfunction and CAD, we analyzed plasma chemerin levels and the estimated glomerular filtration rate (eGFR) in 495 patients undergoing coronary angiography for the evaluation of established or suspected stable CAD.Chemerin levels were higher in patients with Type 2 diabetes mellitus (T2DM, n=111) and the metabolic syndrome (MetS, n=147) than in subjects without T2DM (191.5±72.9 vs. 169.7±64.7ng/ml, p=0.001) or the MetS (201.2±71.0 vs. 163,1ng/ml, p<0.001), but did not differ significantly between patients with significant CAD (n=247) and those without significant CAD (177.1±67.0 vs. 171.7±67.2ng/ml, p=0.193).Analysis of covariance using age, sex, and BMI as covariates showed that chemerin was significantly and independently associated with eGFR (F=49.6, p<0.001). After an 8-year follow-up period, patients with high chemerin levels were more often affected by cardiovascular events (HR=1.72 [95% CI 1.19–2.47], p=0.004), even after appropriate adjustment for age, gender, BMI, as well as eGFR (adjusted HR 1.51 [95% CI 1.03–2.23], p=0.037). Given the cardiometabolic role of chemerin, we also applied a Cardio-Metabo Chip analysis and revealed a genome-wide significant association with SNPs (rs55709438, rs2444030, and rs3098423) located at chromosomal region 15q15–23, which were associated with metabolic traits and eGFR.This study for the first time demonstrates that high chemerin concentrations are significantly associated with renal impairment and predictive of cardiovascular events and that 15q15–23 might have an impact on chemerin levels beyond common genetic variations in RARRES2.

Effects of chemerin on the proliferation of 3T3-L1 adipocytes

To explore the effects of chemerin on the proliferation of 333-Li preadipocytes and elucidate its possible mechanism. Recombinant lentivirus-mediated silencing or over-expression of chemerin gene were constructed in 3T3-L1 cells. The proliferation of 3T3-L1 cells was examined by the assays of methyl thiazolyl tetrazolium (MTT) and 5-bromo-2-deoxyuridine (BrdU) incorporation. The expressions of chemerin, ERK1, ERK2 and cyclinD1 in 3T3-L1 cells were detected by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The protein levels of chemerin, ERK1/2 and p-ERK1/2 were detected by Western blot. MT and BrdU results showed that absorbance (A) value and BrdU incorporation increased in chemerin over-expression group compared with over-expression control group [1. 09 ± 0. 08 vs 0. 90 ± 0. 09, (126. 5 ± 14. 6)% vs (100. 0 ± 7. 0) %, both P <0. 05]. The increase of A value and BrdU incorporation in chemerin over-expression group could be inhibited by PD98059, a blocker of ERK1/2 signal pathway. A value (0. 91 ± 0. 13) and BrdU incorporation [(104. 3 ± 10. 7)%] decreased compared with over-expression group (P <0. 05). They also decreased in chemerin gene silencing group compared to silencing control group [ 0. 72 ± 0. 11 vs 0. 90 ± 0. 09, (77. 6 ± 11. 8) % vs ( 99. 7 ± 6. 3) %, both P < 0. 05]. Quantitative real-time PCR revealed that over-expression group had a higher expression in chemerin, ERK, ERK2 and cyclinDl than over-expression control group (2. 77 ± 0. 31 vs 1. 01 ± 0. 12, 1. 39 ± 0. 19 vs 0. 76 ± 0. 30, 1. 46 ± 0. 14 vs 0. 88 ± 0. 14, 1. 44 ± 0. 17 vs 1. 03 0. 15, all P <0. 05). Chemerin gene silencing group had lower expressions of chemerin, ERKI, ERK2 and cyclinD1 than silencing control group (0. 35 ± 0. 12 vs 1. 25 ± 0. 31, 0. 64 ± 0. 15 vs 1. 03 ± 0. 14, 0. 56 ± 0. 10 vs 1. 06 ± 0. 29, 0. 66 ± 0. 13 vs 1. 09 0. 19, all P <0. 05). Western blot showed that the expressiond of chemerin, ERK1/2 and p-ERK1/2 increased in chemerin over-expression group versus over-expression control group (2. 18 ± 0. 32 vs 1. 18 ± 0. 14, 1. 37 ± 0. 05 vs 0. 97 ± 0. 12, 1. 06 ± 0. 09 vs 0. 56 ± 0. 08, all P < 0. 05). The expressiond of chemerin, ERK1/2 and p-ERK1/2 decreased in chemerin gene silencing group versus silencing control group (1. 00 ± 0. 07 vs 1. 40 ± 0. 17, 0. 87 ± 0. 15 vs 1. 20 ± 0. 12, 0. 49 ± 0. 07 vs 0. 91 ± 0. 11, all P < 0. 05). Chemerin may promote the proliferation of 3T3-L1 cells. And it may be achieved via an up-regulated expression of ERK1/2.

Insulin resistance and adipokines in obese adolescents with acanthosis nigricans

Objective To investigate the clinical characteristics,insulin resistance,and levels of adipokines in obese adolescents with acanthosis nigricans.Methods One hundred and thirty-five obese adolescents and 20 healthy participants were selected.All participants were divided into 3 groups with regard to the acanthosis nigricans:the acanthosis nigricans (AN)group,the simple obesity (Ob)group,and the control group.The clinical characteristics,results of OGTT test and levels of serum adipokines in the participants were recorded.Results The incidence of AN in obese adolescents was 44.4％.Body weight,body mass index,waist circumference,hip circumference,and waist-to-hip ratio were higher in the AN group.Insulin action index (IAI) in the AN group was lower than that in the OB group and control group.However,the level of fasting insulin and HOMA-IR was higher.The level of leptin was higher in the AN group than that in OB group and control group.However,the level of chemerin between the AN group and OB group was similar.Conclusions s AN was a biomarker of severe obesity and insulin resistance in obese adolescents.Higher levels of insulin and leptin might play an important role in the process of AN. Key words: Obesity; Acanthosis nigricans; Adipokines; Insulin resistance

Effects of metformin on chemerin expression in visceral adipose tissue of insulin-resistant rats

After 4 weeks old male Sprague-Dawley rats were fed with normal diet and high-fat diet for 10 weeks,the rats were treated with metformin (200 mg/kg) for 6 weeks. Insulin sensitivity was determined by hyperinsulinemic-euglycemic clamp technique.Realtime PCR and western blot were used to measure mRNA and protein levels of chemerin in perirenal adipose tissue of rats.The results showed that the expressions of chemerin mRNA and protein were higher in high-fat diet-induced insulin resistant rats compared with rats fed with normal diet ( both P＜0.05 ),and these incremental findings were diminished by metformin treatment ( both P＜0.01 ).The levels of chemerin mRNA and protein were correlated well with the epididymis fat mass index. Key words: Chemerin; Metformin; Insulin resistance; Rats; Visceral adipose tissue

Chemerin in hepatocelluar carcinoma: expressions and prognostic values

Objective To study the expressions of Chemerin in hepatocellular carcinoma (HCC) and HCC cell lines,and to demonstrate the relationship between the expressions and prognosis.Methods The expressions of Chemerin protein in normal hepatocellular tissues,HCC and their paired tissues were detected by immunohistochemical staining of SABC; the expressions of Chemerin protein in HCC,cell lines and immortalized hepatocyte cell lines were detected by RT-PCR.Results The positive expression rates of Chemerin were 56.67％,90.00％,100％ in HCC,HCC cell line and normal hepatocellular tissues respectively,and the differences were significant (P＜0.05).The expressions of Chemerin mRNA in HCC paired tissues were higher than in HCC (P＜0.05).There was a higher expression of Chemerin mRNA in immortalized hepatocyte cell line LO2 ; but a lower expression in HCC cell lines.The expressions of Chemerin were related to lymph node metastasis,portal vein tumour thrombi,differentiation and TNM stage but not related to sex,age,tumour size,HBsAg and AFP.Conclusions Down-regulated expression of Chemerin may play an important role in the development,progression and metastasis of HCC.It may be a molecular marker for prognosis of HCC. Key words: Chemerin; Hepatocellular carcinoma; Prognosis

Exploring polymorphisms of the bovine RARRES2 gene and their associations with growth traits

Retinoic acid receptor responder 2 gene (RARRES2) encodes a novel adipokine protein that plays a crucial role in regulating several biological processes, including immune responses, adipocyte differentiation, type 2 diabetes and metabolic syndrome. In this paper, polymorphisms of the bovine RARRES2 gene were detected in 1300 individuals from six breeds by DNA pooling, CRS-PCR-RFLP and DNA sequencing methods. The results showed that NC_007302:g.117035859A>G, 117035706G>A and 117034290A>G were in the coding region, which resulted in three synonymous mutations and only 117033779C>G was in the 3' UTR. Additionally, associations of the four novel SNPs with growth traits were analyzed in Nanyang cattle up to 2 years of age. In P1-PvuII locus, individuals with genotype BC had greater body height and hucklebone width than those with genotype AA, AC and AB at the age of 24 months. In P3-BamHI locus, individuals with genotype AG had higher hucklebone width than those with genotype GG at the age of 24 months. However, no statistically significant differences were observed in P5-SmaI locus. These results indicated that RARRES2 gene might be a potential candidate gene for marker-assisted selection (MAS).

The expression of chemerin and chemerin receptor in rats with methionine-and choline-deficient diet induced nonalcoholic fatty liver disease

Objective To explore the expression of chemerin and chemerin receptor ( chemokine-like receptor 1, CMKLR1) during different periods of non-alcoholic fatty liver disease ( NAFLD) rat model induced by methionine- and choline-deficient ( MCD) diet. Methods Thirty-six Wistar rats were divided into control group and MCD group in random. After one week quarantine and acclimation period, these two groups were fed either normal chow or MCD diet. The animals were respectively sacrificed at the first week, the forth week, and the tenth week. The levels of alanine transaminase (ALT), blood lipid profile, liver function, and the content of triglyceride in liver were detected. HE staining was done to observe the morphologic change of liver. The mRNA expression changes of chemerin and CMKLR1 in liver were measured using real-time PCR, and the change in chemerin mRNA level was further confirmed in liver by Northern blot. Finally, the concentration of chemerin in serum was measured by Western blot. Results The mRNA level of chemerin decreased significantly after four and ten weeks MCD feeding, although no obvious changes were found at first week, similar changes were found in serum chemerin (1.00±0.11 vs 0.96±0.39; 1.00±0.12 vs 0.21 ±0.77; 1.00±0.42 vs 0.21 ±0. 11). Contrasting with the change of chemerin(1.00±0.08 vs 0.72±0.10;1.00±0.24 vs 0.63±0. 31 ;1.00±0.05 vs 0.50±0.13), the mRNA level of CMKLR1 increased after MCD feeding( 1.00±0. 14 vs 0. 84±0. 26; 1.00±0. 38 vs 1. 51 ±0. 33; 1. 01 ±0. 13 vs 1. 84 ± 0. 39 ). Conclusion The change of chemerin and its receptor may participate in the process of the nonalcoholic fatty liver disease. Key words: Methionine- and choline-deficient diet; Chemerin; CMKLR1; Nonalcoholic fatty liver disease

MRNA expressions of chemerin and its receptor 1 in adipose tissue of OLETF rats

The mRNA expressions of chemerin and its receptor CMKLR1 in adipose tissue of OLETF rats and LETO rats were detected by real-time PCR. The results showed that the two genes mRNA expressions in subcutaneous and visceral adipose tissue in OLETF group were significantly higher than those in LETO group (P< 0.05 or P<0.01) and expressions of them in visceral adipose tissue were higher than those in subcutaneous adipose tissue(P<0. 05 or P<0. 01), suggesting that chemerin and CMKLR1 may be involved in the pathogenesis of obesity, insulin resistance, and type 2 diabetes mellitus. Key words: OLETF; Chemerin; CMKLR1; Real-time PCR; Gene expression