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Chemerin is an adipokine that contributes to metabolism regulation. Nucleus tractus solitarius (NTS) is the first relay station in the brain for accepting various visceral afferent activities for regulating cardiovascular activity. However, the roles of chemerin in the NTS in regulating sympathetic activity and blood pressure are almost unknown. This study aimed to determine the role and potential mechanism of chemerin in the NTS in modulating sympathetic outflow and blood pressure. Bilateral NTS microinjections were performed in anaesthetized adult male Sprague–Dawley rats. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) were continuously recorded. Chemerin and its receptor chemokine‐like receptor 1 (CMKLR1) were highly expressed in caudal NTS (cNTS). Microinjection of chemerin‐9 to the cNTS increased RSNA, MAP and HR, which were prevented by CMKLR1 antagonist α‐NETA, superoxide scavenger tempol or N‐acetyl cysteine, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors diphenyleneiodonium or apocynin. Chemerin‐9 increased superoxide production and NADPH oxidase activity in the cNTS. The increased superoxide production induced by chemerin‐9 was inhibited by α‐NETA. The effects of cNTS microinjection of chemerin‐9 on the RSNA, MAP and HR were attenuated by the pretreatment with paraventricular nucleus (PVN) microinjection of NMDA receptor antagonist MK‐801 rather than AMPA/kainate receptor antagonist CNQX. These results indicate that chemerin‐9 in the NTS increases sympathetic outflow, blood pressure and HR via CMKLR1‐mediated NADPH oxidase activation and subsequent superoxide production in anaesthetized normotensive rats. Glutamatergic inputs in the PVN are needed for the chemerin‐9‐induced responses. [ABSTRACT FROM AUTHOR]

Adipose tissues produce a variety of biologically active compounds, including cytokines, growth factors and adipokines. Adipokines are important as they function as endocrine hormones that are related to various metabolic and reproductive diseases. The goal of this review was to summarise the role of asprosin, a recently discovered adipokine, and compare its role in ovarian steroidogenesis with that of other adipokines including adiponectin, leptin, resistin, apelin, visfatin, chemerin, irisin, and gremlin 1. The summary of concentrations of these adipokines in humans, rats and other animals will help researchers identify appropriate doses to test in future studies. Review of the literature indicated that asprosin increases androstenedione production in theca cells (Tc), and when cotreated with FSH increases oestradiol production in granulosa cells (Gc). In comparison, other adipokines (1) stimulate Gc oestradiol production but inhibit Tc androgen production (adiponectin), (2) inhibit Gc oestradiol production and Tc androstenedione production (leptin and chemerin), (3) inhibit Gc steroidogenesis with no effect on Tc (resistin), (4) inhibit Gc oestradiol production but stimulate Tc androgen production (gremlin 1), and (5) increase steroid secretion by Gc, with unknown effects on Tc steroidogenesis (apelin and visfatin). Irisin has direct effects on Gc but its precise role (inhibitory or stimulatory) may be species dependent and its effects on Tc will require additional research. Thus, most adipokines have direct effects (either positive or negative) on steroid production in ovarian cells, but how they all work together to create a cumulative effect or disease will require further research. Adipose tissues produce a variety of biologically active compounds including adipokines, which function as endocrine hormones that are linked to various metabolic and reproductive diseases. The goal of this review was to provide an up-to-date summary of the role of some of these adipokines in mammalian reproduction and how they regulate ovarian steroid production. Understanding the effects of these adipokines on ovarian function will help formulate solutions for improved reproductive efficiency. Image by Leon Spicer. [ABSTRACT FROM AUTHOR]

We investigated the effects of tobacco smoke exposure and abnormal body weight on selected peptide hormones and their association with metabolic and hormonal disorders in women with polycystic ovary syndrome (PCOS). The study group included 88 women with PCOS and 28 women without the disease. In women with PCOS, chemerin, lipocalin, and apelin concentrations were influenced by overweight and obesity status, with the highest concentrations observed in those with a body mass index (BMI) ≥ 30.0. Exposure to tobacco smoke significantly increased only lipocalin-2 concentration. The disease itself did not affect the concentrations of chemerin, lipocalin, and apelin. Additionally, we found a positive correlation between chemerin concentration and fasting glucose, fasting insulin, and triglycerides levels, while a negative correlation was observed with high-density lipoprotein (HDL-C) concentration. In the smoking subgroup, chemerin concentration was positively correlated with free testosterone concentration and the free androgen index and negatively associated with sex hormone-binding globulin concentration. Our findings indicate that abnormal body weight has a stronger impact than tobacco smoke exposure on metabolic and hormonal disorders in women with PCOS, highlighting the important role of weight control in such individuals. However, smoking appears to be an additional factor that intensifies hormonal disorders associated with adipose tissue. [ABSTRACT FROM AUTHOR]

Introduction: Human chemerin is an adipokine that regulates chemotaxis, inflammation, and glucose metabolism. In addition, accumulating evidence suggests that chemerin promotes apoptosis, autophagy, and pyroptosis. However, there are no data on its impact on eryptosis. The current study aimed to analyze the effects of human active Glu-Ser chemerin on eryptosis in vitro. Materials and Methods: Human chemerin 0-2-10-50 µg/mL was incubated for 24 h with human erythrocytes (hematocrit 0.4%) obtained from eight healthy individuals. Flow cytometry-based determination of phospholipid scrambling, reactive oxygen species (ROS) production, and intracellular Ca levels was performed. To supplement data on ROS and Ca signaling in chemerin-mediated eryptosis, incubation in the presence or absence of antioxidants vitamin C and N-acetylcysteine and Ca-binding agent EGTA was carried out, respectively. Confocal microscopy-based techniques were used to detect reactive nitrogen species (RNS) generation, involvement of caspase-3 and caspase-8, as well as the state of lipid order in cell membranes of erythrocytes exposed to human Glu-Ser chemerin. Results: Our observations suggest that human Glu-Ser chemerin had no impact on eryptosis parameters at 2 µg/mL. However, chemerin stimulated phosphatidylserine externalization, ROS production, and Ca accumulation at higher concentrations suggesting activation of eryptosis. Ca uptake turned out to be at least partly required for chemerin-mediated eryptosis. Chemerin-mediated erythrotoxicity was additionally mediated by RNS, caspase-3, and caspase-8. Moreover, Glu-Ser chemerin promoted reduction in the liquid-ordered phase of cell membranes in erythrocytes. Conclusions: The present study first discloses that human chemerin can induce eryptosis via Ca-dependent mechanisms at concentrations noticeably exceeding circulating levels. Thus, chemerin-induced eryptosis can hardly contribute to eryptosis-mediated anemia in diseases associated with enhanced levels of chemerin in blood. [ABSTRACT FROM AUTHOR]

Introduction: Observational studies have demonstrated strong correlations between metabolic syndrome (MetS) and its related traits. To gain insight into the genetic architecture and molecular mechanism of MetS, we investigated the shared genetic basis of MetS and its related traits and further tested their causal relationships. Methods: Using summary statistics from genome-wide association analyses of about 72,000 subjects from the Korean Genome and Epidemiological Study (KoGES), we conducted genome-wide multi-trait analyses to quantify the overall genetic correlation and Mendelian randomization analyses to infer the causal relationships between traits of interest. Results: Genetic correlation analyses revealed a significant correlation of MetS with its related traits, such as obesity traits (body mass index and waist circumference), lipid traits (triglyceride and high-density lipoprotein cholesterol), glycemic traits (fasting plasma glucose and hemoglobin A1C), and blood pressure (systolic and diastolic). Mendelian randomization analyses further demonstrated that the MetS-related traits showing significant overall genetic correlation with MetS could be genetically determined risk factors for MetS. Discussion: Our study suggests a shared genetic basis of MetS and its related traits and provides novel insights into the biological mechanisms underlying these complex traits. Our findings further inform public health interventions by supporting the important role of the management of metabolic risk factors such as obesity, unhealthy lipid profiles, diabetes, and high blood pressure in the prevention of MetS. [ABSTRACT FROM AUTHOR]

Adipokines play essential roles in regulating a range of biological processes, but growing evidence indicates that they are also fundamental in immunological mechanisms and, primarily, inflammatory responses. Adipokines mediate their actions through specific receptors. However, although adipokine receptors are widely distributed in many cell and tissue types, limited data are available on their expression in mast cells (MCs) and, consequently, adipokine's significance in the modulation of MC activity within the tissues. In this study, we demonstrate that rat peritoneal MCs constitutively express the leptin receptor (i.e. LEPR), adiponectin receptors (i.e. ADIPOR1 and ADIPOR2) and the chemerin receptor (i.e. CMKLR1). We also found that LEPR, ADIPOR1, ADIPOR2 and CMKLR1 expression in MCs changes in response to stimulation by their specific ligands and some cytokines with potent proinflammatory properties. Furthermore, the involvement of intracellular signaling molecules in leptin‐, adiponectin‐ and chemerin‐induced MC response was analyzed. Overall, our findings suggest that adipokines leptin, adiponectin and chemerin can significantly affect the activity of MCs in various processes, especially during inflammation. These observations may contribute significantly to understanding the relationship between adipokines, immune mechanisms and diseases or conditions with an inflammatory component. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM) is a major public health concern worldwide. Although there are many possible causes of diabetes, the three most prevalent ones are insulin resistance, pancreatic cell damage, and insulin insufficiency. Visfatin, an adipocytokine with insulin-mimicking characteristics, and chemerin, an adipokine responsible for maintaining normal cholesterol and glucose levels, are linked to inflammation and immunological dysfunction in metabolic illnesses. Hence, in this study, we aimed to evaluate the possible association between type 2 diabetes mellitus (T2DM) and the adipokines visfatin and chemerin. Methods and Results: This study was conducted at the Al-Salam Teaching Hospital in Mosul from December 1, 2022, to the end of June 2023. The study included 65 patients of both sexes with T2DM aged between 35 and 80. Twenty-five healthy individuals of both sexes were chosen for a control group. Visfatin and chemerin levels in the serum were measured using an ELISA kit (Koma biotech, ELISA, USA) per the manufacturer's instructions. The levels of visfatin and chemerin in T2DM patients were significantly higher than in controls (1.478±0.631ng/ml and 158.768±36.941pg/ml vs. 0.538±0.151ng/ml and 71.272±12.994pg/ml, respectively, P=0.000 in both cases). The study showed no significant difference in the levels of chemerin and visfatin between females and males in T2DM patients. Among men, the visfatin levels were significantly higher in T2DM patients with diabetic retinopathy than in T2DM patients with such complications as cardiovascular disease and diabetic nephropathy. These features also occurred among women. Men and women with T2DM did not differ in the chemerin levels, depending on the nature of the diabetes complication. Conclusion: T2DM patients are characterized by significantly higher visfatin and chemerin levels than healthy controls. No differences in the levels of these adipokines that depend on the gender of diabetic patients have been found.

Induction of beige fat for thermogenesis is a potential therapy to improve homeostasis against obesity. β3-adrenoceptor (β3-AR), a type of G protein-coupled receptor (GPCR), is believed to mediate the thermogenesis of brown fat in mice. However, β3-AR has low expression in human adipose tissue, precluding its activation as a standalone clinical modality. This study aimed at identifying a potential GPCR target to induce beige fat. We found that chemerin chemokine-like receptor 1 (CMKLR1), one of the novel GPCRs, mediated the development of beige fat via its two ligands, chemerin and resolvin E1 (RvE1). The RvE1 levels were decreased in the obese mice, and RvE1 treatment led to a substantial improvement in obese features and augmented beige fat markers. Inversely, despite sharing the same receptor as RvE1, the chemerin levels were increased in obesogenic conditions, and chemerin treatment led to an augmented obese phenotype and a decline of beige fat markers. Moreover, RvE1 and chemerin induced or restrained the development of beige fat, respectively, via the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. We further showed that RvE1 and chemerin regulated mTORC1 signaling differentially by forming hydrogen bonds with different binding sites of CMKLR1. In conclusion, our study showed that RvE1 and chemerin affected metabolic homeostasis differentially, suggesting that selectively modulating CMKLR1 may be a potential therapeutic target for restoring metabolic homeostasis.

The adipokine chemerin contributes to exercise-induced improvements in glucose and lipid metabolism; however, the underlying mechanism remains unclear. We aimed to confirm the impact of reduced chemerin expression on exercise-induced improvement in glycolipid metabolism in male diabetic (DM) mice through exogenous chemerin administration. Furthermore, the underlying mechanism of chemerin involved in changes in muscle mitochondria function mediated by androgen/androgen receptor (AR) was explored by generating adipose-specific and global chemerin knockout (adipo-chemerin−/− and chemerin−/−) mice. DM mice were categorized into the DM, exercised DM (EDM), and EDM + chemerin supplementation groups. Adipo-chemerin−/− and chemerin−/− mice were classified in the sedentary or exercised groups and fed either a normal or high-fat diet. Exercise mice underwent a 6-wk aerobic exercise regimen. The serum testosterone and chemerin levels, glycolipid metabolism indices, mitochondrial function, and protein levels involved in mitochondrial biogenesis and dynamics were measured. Notably, exogenous chemerin reversed exercise-induced improvements in glycolipid metabolism, AR protein levels, mitochondrial biogenesis, and mitochondrial fusion in DM mice. Moreover, adipose-specific chemerin knockout improved glycolipid metabolism, enhanced exercise-induced increases in testosterone and AR levels in exercised mice, and alleviated the detrimental effects of a high-fat diet on mitochondrial morphology, biogenesis, and dynamics. Finally, similar improvements in glucose metabolism (but not lipid metabolism), mitochondrial function, and mitochondrial dynamics were observed in chemerin−/− mice. In conclusion, decreased chemerin levels affect exercise-induced improvements in glycolipid metabolism in male mice by increasing mitochondrial number and function, likely through changes in androgen/AR signaling. NEW & NOTEWORTHY: Decreased chemerin levels affect exercise-induced improvements in glycolipid metabolism in male mice by increasing mitochondrial number and function, which is likely mediated by androgen/androgen receptor expression. This study is the first to report the regulatory mechanism of chemerin in muscle mitochondria. [ABSTRACT FROM AUTHOR]

The lipid profile and adipokines of an adolescent may be affected by some parasite infections. Recently, it has been discovered that these parasites are connected to body mass index (BMI), lipids and adipokines. The current study, therefore, aimed to specify how Toxoplasma gondii (T. gondii) affect BMI, lipid profile and adipokines. This study was conducted in Al Madain hospital, Baghdad from October to December 2022. An ELISA test was performed to examine the antiT. gondii IgG and IgM for a group of adolescents attending the hospital. Based on this examination ninety adolescents were chosen to be involved in the study. They were separated in to two groups: individuals who tested positive for the parasite (n=45) and those who tested negative for the parasite, control group (n=45). All participating adolescents were subjected to some measurements which included body mass index (BMI), lipid profile parameters (cholesterol, triglycerides, HDL, LDL, and VLD) and adipokines (adiponectin and chemerin). Significant high BMI was noticed in T. gondii positive group (29.65±0.6 Kg/m²) compared to control. The results also indicated that there was a significant increase in all tests of the lipid profile among T. gondii positive group compared to the control. However, the matter reversed in HDL examination as its level increased significantly in the control compared to the T. gondii positive group. Finally, both adiponectin (78.6±0.037 ng/ml) and chemerin (3.43±0.1 ng/ml) raised up significantly in T. gondii positive group versus control group. [ABSTRACT FROM AUTHOR]

Chemerin acts as both a chemotactic agent and an adipokine that undergoes proteolytic cleavage, converting inactive precursors into their active forms before being subsequently inactivated. Elevated chemerin levels are linked to obesity and type 2 diabetes mellitus (T2D). This study aimed to elucidate the effects of T2D and obesity on chemerin levels by comparing plasma samples from individuals with a normal weight and T2D (BMI < 25; NWD group n = 22) with those from individuals who are overweight or obese and have T2D (BMI ≥ 25; OWD group n = 39). The total chemerin levels were similar in the NWD and OWD groups, suggesting that T2D may equalize the chemerin levels irrespective of obesity status. The cleavage of chemerin has been previously linked to myocardial infarction and stroke in NWD, with potential implications for inflammation and mortality. OWD plasma exhibited lower levels of cleaved chemerin than the NWD group, suggesting less inflammation in the OWD group. Here, we showed that the interaction between obesity and T2D leads to an equalization in the total chemerin levels. The cleaved chemerin levels and the associated inflammatory state, however, differ significantly, underscoring the complex relationship between chemerin, T2D, and obesity. [ABSTRACT FROM AUTHOR]

Recruitment and accumulation of reactive astrocytes around senile plaques are common pathological features of Alzheimer's disease (AD), with unclear mechanisms. Chemerin, an adipokine implicated in neuroinflammation, acts through its receptor, chemokine-like receptor 1 (CMKLR1), which also functions as a receptor for amyloid β (Aβ). The impact of the chemerin/CMKLR1 axis on astrocyte migration towards Aβ plaques is unknown. Here we investigated the effect of CMKLR1 on astrocyte migration around Aβ deposition in APP/PS1 mice with Cmklr1 knockout (APP/PS1-Cmklr1−/−). CMKLR1-expressed astrocytes were upregulated in the cortices and hippocampi of 9-month-old APP/PS1 mice. Chemerin mainly co-localized with neurons, and its expression was reduced in the brains of APP/PS1 mice, compared to WT mice. CMKLR1 deficiency decreased astrocyte colocalization with Aβ plaques in APP/PS1-Cmklr1−/− mice, compared to APP/PS1 mice. Activation of the chemerin/CMKLR1 axis promoted the migration of primary cultured astrocytes and U251 cells, and reduced astrocyte clustering induced by Aβ42. Mechanistic studies revealed that chemerin/CMKLR1 activation induced STING phosphorylation. Deletion of STING attenuated the promotion of the chemerin/CMKLR1 axis relative to astrocyte migration and abolished the inhibitory effect of chemerin on Aβ42-induced astrocyte clustering. These findings suggest the involvement of the chemerin/CMKLR1/STING pathway in the regulation of astrocyte migration and recruitment to Aβ plaques/Aβ42. [ABSTRACT FROM AUTHOR]

Adipose tissue is an active endocrine gland, synthesizing and secreting multiple signaling molecules termed adipokines. Following the detection of adipokines and their receptors in the mammary tissue of various species, it is indicated that adipokines play a role in the development of the mammary gland. The aim of the present study was to determine the concentration-dependent influence of three adipokines, leptin, adiponectin, and chemerin, on the viability, apoptosis, and secretory activity of BME-UV1 bovine mammary epithelial cells. The study confirmed that BME-UV1 cells contain the leptin receptor (Ob-R) protein, and express transcripts of adiponectin (ADIPOR1 and ADIPOR2) and chemerin (CMLKR1 and GPR1) receptors. Regardless of the administered dose, none of the three tested adipokines had an effect on the viability of BME-UV1 cells, and the number of apoptotic cells remained unchanged. However, chemerin (100 ng/mL) stimulated BME-UV1 cells to synthesize and secrete αS1-casein, the major protein component of milk. These results indicate that chemerin may be a potent regulator of the bovine mammary epithelial cells' functional differentiation, contributing, along with the major systemic hormones and local growth factors, to the development of the bovine mammary gland. [ABSTRACT FROM AUTHOR]

Endovascular stenting is a safer alternative to open surgery for use in treating cerebral arterial stenosis and significantly reduces the recurrence of ischemic stroke, but the widely used bare-metal stents (BMSs) often result in in-stent restenosis (ISR). Although evidence suggests that drug-eluting stents are superior to BMSs in the short term, their long-term performances remain unknown. Herein, we propose a potential vascular stent modified by immobilizing clickable chemerin 15 (C15) peptides on the stent surface to suppress coagulation and restenosis. Various characterization techniques and an animal model were used to evaluate the surface properties of the modified stents and their effects on endothelial injury, platelet adhesion, and inflammation. The C15-immobilized stent could prevent restenosis by minimizing endothelial injury, promoting physiological healing, restraining the platelet-leukocyte-related inflammatory response, and inhibiting vascular smooth muscle cell proliferation and migration. Furthermore, in vivo studies demonstrated that the C15-immobilized stent mitigated inflammation, suppressed neointimal hyperplasia, and accelerated endothelial restoration. The use of surface-modified, anti-inflammatory, endothelium-friendly stents may be of benefit to patients with arterial stenosis. Endovascular stenting is increasingly used for cerebral arterial stenosis treatment, aiming to prevent and treat ischemic stroke. But an important accompanying complication is in-stent restenosis (ISR). Persistent inflammation has been established as a hallmark of ISR and anti-inflammation strategies in stent modification proved effective. Chemerin 15, an inflammatory resolution mediator with 15-aa peptide, was active at picomolar through cell surface receptor, no need to permeate cell membrane and involved in resolution of inflammation by inhibiting inflammatory cells adhesion, modulating macrophage polarization into protective phenotype, and reducing inflammatory factors release. The implications of this study are that C15 immobilized stent favors inflammation resolution and rapid re-endothelialization, and exhibits an inhibitory role of restenosis. As such, it helps the decreased incidence of ISR. [Display omitted] [ABSTRACT FROM AUTHOR]

Chemerin is a newly discovered adipokine that binds to its high-affinity receptor ChemR23 and participates extensively in the regulation of various physiological processes. Studies have confirmed that the Chemerin/ChemR23 signaling pathway is highly relevant to bone metabolism regulation. It mainly regulates bone metabolism by modulating key signaling pathways including MAPK, PI3K/Akt, Wnt/B-catenin, NF-kB, and regulating testosterone synthesis. This article reviews the research progress on the Chemerin/ChemR23 signaling pathway in bone metabolism regulation and its correlation with osteoporosis, to improve the clinical understanding of the relevance between Chemerin/ChemR23 signaling pathway and bone metabolic diseases. [ABSTRACT FROM AUTHOR]

Obesity-induced insulin resistance (IR) is known to influence hepatic cytokines (hepatokines), including fibroblast growth factor (FGF-21), fetuin-A, and chemerin. This study aimed to investigate the association between hepatokines and markers of endothelial dysfunction and vascular reactivity in obese adolescents. A total of 45 obese adolescents were categorized into three groups based on glucose tolerance: normal glucose tolerance (NGT), prediabetes (PD), and type 2 diabetes (T2D). We examined the relationships between FGF-21, fetuin-A, and chemerin with endothelial markers (plasminogen activator inhibitor-1 [PAI-1], intercellular adhesion molecule-1 [ICAM-1], and vascular cell adhesion marker-1 [VCAM-1]) and vascular surrogates (brachial artery reactivity testing [BART] and peak reactive hyperemia [PRH]). Obese adolescents (age 16.2±1.2 years; 62 % female, 65 % Hispanic) with NGT (n=20), PD (n=14), and T2D (n=11) had significant differences between groups in BMI; waist-hip ratio (p=0.05), systolic BP (p=0.008), LDL-C (p=0.02), PAI-1 (p<0.001). FGF-21 pg/mL (mean±SD: NGT vs. PD vs. T2D 54±42; 266±286; 160±126 p=0.006) and fetuin-A ng/mL (266±80; 253±66; 313±50 p=0.018), were significantly different while chemerin ng/mL (26±5; 31±10; 28±2) did not significantly differ between the groups. Positive correlations were found between chemerin and both PAI-1 (r=0.6; p=0.05) and ICAM-1 (r=0.6; p=0.05), FGF-21 and PAI-1 (r=0.6; p<0.001), and fetuin-A with TNFα (r=−0.4; p=0.05). Negative correlations were found between chemerin and PRH (r= −0.5; p=0.017) and fetuin-A and PRH (r=−0.4; p=0.05). In our cohort, IR predicted higher FGF-21 levels suggesting a linear relationship may exist between the two parameters. Hepatokines can augment alterations in the microvascular milieu in obese adolescents as demonstrated by their associations with the markers PAI-1, ICAM-1, and PRH. [ABSTRACT FROM AUTHOR]

Context A subset of polycystic ovary syndrome (PCOS) individuals also have type 2 diabetes (T2D); an unmet need to identify this subgroup exists. Objective We looked at the potential role of serum chemerin, a proinflammatory adipokine, in identifying dysglycemic PCOS. Methods A total of 93 PCOS and 33 healthy controls were classified, based on fasting and 2-hour plasma glucose levels (2hPGPG) and glycated hemoglobin A1c (HbA1c) (%) into normoglycemic (n = 34), dysglycemic (n = 33), and T2D (n = 26). Serum chemerin were measured by enzyme-linked immunosorbent assay. Homeostatic model 2 assessment of insulin resistance (HOMA-2IR) and homeostatic model 2 assessment of β-cell function (HOMA-2β) were computed using serum C-peptide. Results Metabolic syndrome was present in 9.7% (National Cholesterol Education Program) of PCOS. Waist circumference, body fat (%), 2hPGPG, and HbA1c levels were significantly higher in T2D group. Serum triglycerides/high-density lipoprotein cholesterol (TGs/HDL-c) ratio was increased in PCOS individuals with T2D; no significant changes in total cholesterol and LDL-c levels were seen. Serum chemerin levels were significantly higher (P <.001) in the PCOS group. Total body fat (%), 2hPGPG, HbA1c, and TG/HDL-c ratio correlated positively with chemerin levels. Serum chemerin levels correlated positively with HOMA2IR and negatively with HOMA-2β. On receiver operating characteristic curve analysis, a serum chemerin cutoff level of greater than 309.3 ng/mL differentiated PCOS individuals with dysglycemia from those without (sensitivity 85.71%, specificity 89.47%). The Cohen kappa test revealed a substantial agreement (P <.001) between chemerin cutoff and 2hPGPG levels greater than 200 mg/dL. The present study is arguably the first ever to define a serum chemerin cutoff to distinguish PCOS individuals with T2D from those without. Conclusion Elevated serum chemerin levels reliably identify PCOS individuals with dysglycemia. Further, longitudinal studies with larger samples are required to confirm this association. [ABSTRACT FROM AUTHOR]

Chemerin is a chemokine/adipokine, regulating inflammation, adipogenesis and energy metabolism whose activity depends on successive proteolytic cleavages at its C-terminus. Chemerin levels and processing are correlated with insulin resistance. We hypothesized that chemerin processing would be higher in individuals with type 2 diabetes (T2D) and in those who are insulin resistant (IR). This hypothesis was tested by characterizing different chemerin forms by specific ELISA in the plasma of 18 participants with T2D and 116 without T2D who also had their insulin resistance measured by steady-state plasma glucose (SSPG) concentration during an insulin suppression test. This approach enabled us to analyze the association of chemerin levels with a direct measure of insulin resistance (SSPG concentration). Participants were divided into groups based on their degree of insulin resistance using SSPG concentration tertiles: insulin sensitive (IS, SSPG ≤ 91 mg/dL), intermediate IR (IM, SSPG 92–199 mg/dL), and IR (SSPG ≥ 200 mg/dL). Levels of different chemerin forms were highest in patients with T2D, second highest in individuals without T2D who were IR, and lowest in persons without T2D who were IM or IS. In the whole group, chemerin levels positively correlated with both degree of insulin resistance (SSPG concentration) and adiposity (BMI). Participants with T2D and those without T2D who were IR had the most proteolytic processing of chemerin, resulting in higher levels of both cleaved and degraded chemerin. This suggests that increased inflammation in individuals who have T2D or are IR causes more chemerin processing. [ABSTRACT FROM AUTHOR]

ABSTRACT: Embryonic mortality is a significant problem in the commercial duck industry worldwide. Therefore, identification of new biomarkers for duck embryo development is necessary. In the chicken (order Galliformes), we previously showed that chemerin is a hormone locally produced by the reproductive tract in hens, particularly in the magnum area, leading to its accumulation in the egg white and within the embryo annexes during embryonic development. We therefore hypothesized that the chemerin concentration in egg white could be a biomarker of egg performance and reproductive parameters in Pekin ducks (order Anseriformes). Thus, we collected eggs from Pekin ducks over a 5-d period at three stages of the laying period (before the laying peak, after the laying peak, and at the end of the laying period) to measure the chemerin concentrations in egg white by enzyme-linked immunosorbent assay. The chemerin concentration in egg white decreased during the laying period and was not associated with reproductive parameters. We found negative correlations between the chemerin level in egg white and the albumen weight. Reverse-transcriptase quantitative polymerase chain reaction showed that chemerin and its three receptors CMKLR1, GPR1, and CCRL2 were expressed in the reproductive tract and within allantoic and amniotic annexes during embryo development. Chemerin concentrations strongly increased in amniotic fluid on embryonic day 16 (ED16) when the egg white was transferred into the amniotic sac. Finally, chemerin inhibition in egg white by in ovo injections of anti-chemerin antibodies (0.01, 0.1, and 1 µg) increased the embryo mortality rate. These data demonstrate the important role of the chemerin system during egg formation and embryo development in Pekin ducks, suggesting their potential use as biomarkers for determining the quality of poultry eggs and embryo development.

Adipokine chemerin plays important roles in disorders of glucose and lipid metabolism of obesity and obesity-related diseases, and exercise-induced improvement of glucose and lipid metabolism is closely related to the decrease of chemerin, but the mechanisms by which chemerin regulates glucose and lipid metabolism remain unclarified. Hypotestosterone induces male obesity and disorders of glucose and lipid metabolism through androgen receptor (AR) and its target genes: glucose and lipid metabolism-related molecules (including FOXO1, PEPCK, PGC-1α, and SCD1). Recently, the link between them has been reported that chemerin modulated the secretion of androgen. In this study, global chemerin knockout (chemerin (−/−)) mice were established to demonstrate the roles of chemerin in regulating blood glucose and blood lipid of mice under diet (high-fat (HFD) and normal diet) and exercise interventions and then to explore its mechanisms (AR – glucose and lipid metabolism enzymes). We found that the blood lipid and adipocyte size were low accompanied by the improvements in the levels of serum testosterone, gastrocnemius AR, and gastrocnemius FOXO1, SCD1, and PGC-1α in HFD chemerin (−/−) mice, but exercise-induced improvements of these indicators in HFD WT mice were attenuated or abolished in HFD chemerin (−/−) mice. In conclusion, the decrease of chemerin improved the blood lipid profile of HFD male mice at sedentary and exercise states, mediated partly by the increases of testosterone and AR to regulate glucose and lipid metabolism enzymes. To our knowledge, it is the first report that chemerin’s regulation of glucose and lipid metabolism might be mediated by testosterone and AR in vivo.

Aims: Elevated levels of adipokine chemerin have been identified in oral squamous cell carcinoma (OSCC) and found to be associated with metastasis to the cervical lymph nodes. The underlying mechanism through which chemerin affects OSCC progression is unclear. The aims of this study were firstly to determine chemerin levels and cytokine concentrations in serum from patients with OSCC and in OSCC cell cultures, and secondly to observe chemerin effects on OSCC cell cytokine secretion, migration, and invasion in vitro. Methods: Serum samples were collected from 20 patients diagnosed with OSCC, including groups with (LN+) and without (LN-) cervical lymph node metastasis. A Luminex liquid suspension assay was used to quantify serum concentrations of 27 types of cytokines. Correlations between chemerin and cytokines (i.e., IL-6, IL-15, GM-CSF, RANTES, TNF-α, and VEGF) were analyzed. ELISAs (enzyme-linked immunosorbent assays) were used to determine concentrations of chemerin and selected cytokines in serum and in supernatants of OSCC cell cultures (SCC9 and SCC25 cell lines). OSCC cells were stimulated with human recombinant chemerin, STAT3 inhibitor, or IL-6 together with TNF-α neutralizing antibodies. Phosphorylated STAT3 protein levels were measured with western blot analysis. OSCC cell migration and invasion were investigated with Transwell assays. Results: Compared to the LN- group, OSCC patients with cervical lymph node metastasis had higher levels of IL-6 (P = 0.006), IL-15 (P = 0.020), GM-CSF (P = 0.036), RANTES (P = 0.032), TNF-α (P = 0.005), VEGF (P = 0.006), and chemerin (P = 0.001). Patients' serum chemerin levels correlated directly with IL-6, GM-CSF, TNF-α, and VEGF levels in OSCC patients. Exogenous recombinant chemerin treatment promoted secretion of IL-6 and TNF-α via activation of STAT3 in OSCC cells. Chemerin induced OSCC-cell migration and invasion, and these effects were reduced by IL-6 and TNF-α neutralizing antibodies. Conclusion: Our findings indicate that chemerin may play a role in advancing OSCC progression by increasing production of IL-6 and TNF-α, perhaps via a mechanism involving STAT3 signaling. [ABSTRACT FROM AUTHOR]

The prevalence of osteoporosis has been on the rise globally. With ageing populations, research has sought therapeutic solutions in novel areas. One such area is that of the adipokines. Current literature points to an important role for these chemical mediators in relation to bone metabolism. Wellestablished adipokines have been broadly reported upon. These include adiponectin and leptin. However, other novel adipokines such as visfatin, nesfatin-1, meteorin-like protein (Metrnl), apelin and lipocalin-2 are starting to be addressed pre-clinically and clinically. Adipokines hold pro-inflammatory and anti-inflammatory properties that influence the pathophysiology of various bone diseases. Omentin-1 and vaspin, two novel adipokines, share cardioprotective effects and play essential roles in bone metabolism. Studies have reported boneprotective effects of omentin-1, whilst others report negative associations between omentin-1 and bone mineral density. Lipocalin-2 is linked to poor bone microarchitecture in mice and is even suggested to mediate osteoporosis development from prolonged disuse. Nesfatin-1, an anorexigenic adipokine, has been known to preserve bone density. Animal studies have demonstrated that nesfatin-1 treatment limits bone loss and increases bone strength, suggesting exogenous use as a potential treatment for osteopenic disorders. Pre-clinical studies have shown adipokine apelin to have a role in bone metabolism, mediated by the enhancement of osteoblast genesis and the inhibition of programmed cell death. Although many investigations have reported conflicting findings, sufficient literature supports the notion that adipokines have a significant influence on the metabolism of bone. This review aims at highlighting the role of novel adipokines in osteoporosis while also discussing their potential for treating osteoporosis. [ABSTRACT FROM AUTHOR]

Depressive disorder is a complex mental health condition in which the etiopathogenesis involves several factors. Suitable biomarkers for the development of depression have not yet been established. Alterations in cytokines are assumed to be involved in the pathophysiology of depressive disorder. Adipokines (also known as adipocytokines) are important factors that not only regulate the energy balance but also regulate the inflammatory and immune responses. This study investigated the serum levels of adiponectin, leptin, resistin, chemerin, and fetuin A and the possible role of these adipokines in depressive disorder. We recruited a total of 73 patients diagnosed with recurrent depressive disorder (rDD) and 54 age- and sex-matched healthy controls (HCs). Serum adipocytokines were determined using ELISA kits (R&D, USA). The serum levels of the investigated molecules between depressive patients and HCs were compared, and diagnostic values were evaluated using the receiver operating characteristic (ROC) curve method for discriminating depressive patients from HCs. Correlations between the molecules and clinical variables were also evaluated. Patients with rDD had lower levels of serum adiponectin and chemerin and higher levels of serum leptin, resistin and fetuin A (p < 0.05) vs. controls. Moreover, ROC curve analysis showed that the area under the curve (AUC) values of above set of adipocytkines were >0.7, with a sensitivity and specificity over 80% in discriminating patients with rDD from HCs. Conclusions: These results suggest that circulating adipocytokies may hold promise as biomarkers for the diagnosis of rDD. [ABSTRACT FROM AUTHOR]

Introduction: Lung cancer is the most commonly diagnosed cancer with 2.2 million cases in 2020 and causes 1.8 million deaths. Early lung cancer often has no symptoms and can only be detected by medical imaging. When symptoms do appear, they are often respiratory problems --coughing, breathlessness or chest pain -- and systemic problems -- loss of appetite, weight loss, general weakness, fever and night sweats. There are two main types of lung cancer: small cell lung cancer (SCLC; 15% of cases) and non-small cell lung cancer (NSCLC; 85% of cases). Material and methods: This study included evaluation of CMKLR1, PD-1, B7H3, B7H4 and HHLA2 expression, along with CD8 + T-cell population, TILs and budding in H + E stained slides using IHC. Although there was no clear association between the analysed expressions and the T parameter, this study, which included 22 archived lung adenocarcinoma cases from patients undergoing radical lobectomy, revealed significant negative correla- tions between HHLA2 expression and tumour grade, as well as between CMKLR1 expression and tumour grade. Results: Furthermore, CMKLR1 expression among lymphocytes showed a positive correlation with TILs. [ABSTRACT FROM AUTHOR]

The aim: To study the relationship between lipid metabolism parameters, chemerin, and adenosine monophosphate-activated protein kinase (AMPK) activity in patients with type 2 diabetes mellitus (T2DM), as well as in patients with a combined course of T2DM and gout. Materials and methods. To assess lipid metabolism disorders, 100 patients were examined and divided into 2 groups: 1st group - patients with T2DM and gout (n=70), 2nd group - patients with gout (n=30), control group (CG) - practically healthy individuals (n=20). The levels of total cholesterol (TC), triglycerides, highdensity lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and very low-density lipoprotein cholesterol (VLDL) were analyzed. As markers of insulin resistance (IR), the content of AMPK and chemerin was investigated. Statistical data processing was carried out using the statistical data processing program package version 8.0 STATISTICA (StatSoft Inc). The results. A significant difference was found between the levels of lipid parameters (except HDL) when comparing patients with the combined pathology of T2DM and gout, with a monocourse of gout and representatives of CG (р<0.001). It was also found that among lipidogram indicators, in all groups, an inverse correlation of AMPK value with LDL level was found (strong for patients of the 1st group and medium strength for representatives of the 2nd group and CG). Another indicator with which AMPK levels in all groups were statistically reliably correlated was TC. The presence of a direct correlation between the levels of LDL and chemerin in the 2nd group and CG, as well as the levels of TC and chemerin in patients with a combination of T2DM with gout and an inverse correlation in the other groups (all p<0.05) was established. Conclusions: Statistically significant relationships were found between lipid metabolism indicators, chemerin and AMPK activity in patients with T2DM, as well as in patients with combined course of T2DM and gout. [ABSTRACT FROM AUTHOR]

Background: Moyamoya disease (MMD) has attracted the attention of scholars because of its rarity and unknown etiology. Methods: Data for this study were sourced from the Second Affiliated Hospital of Nanchang University. Regression analyses were conducted to examine the association in Lipoprotein [Lp(a)] and MMD. R and IBM SPSS were conducted. Results: A cohort comprising 1012 MMD patients and 2024 controls was established through the propensity score matching method. Compared with controls, MMD patients showed higher median Lp(a) concentrations [18.5 (9.6–37.8) mg/dL vs. 14.9 (7.8–30.5) mg/dL, P < 0.001]. The odds ratios and 95% confidence intervals for Lp(a) were calculated in three models: unadjusted model, model 1 (adjusted for body mass index and systolic blood pressure), and model 2 (adjusted for model 1 plus triglyceride, C-reactive protein, homocysteine, and low-density lipoprotein cholesterol). Results were [1.613 (1.299–2.002), P < 0.001], [1.598 (1.286–1.986), P < 0.001], and [1.661 (1.330–2.074), P < 0.001], respectively. Furthermore, age, sex, or hypertension status had nothing to do with this relationship. Conclusions: Positive relationship exists between Lp(a) and MMD. [ABSTRACT FROM AUTHOR]

Chemerin is an atypical chemokine first described as a chemoattractant agent for monocytes, natural killer cells, plasmacytoid and myeloid dendritic cells, through interaction with its main receptor, the G protein-coupled receptor chemokine-like receptor 1 (CMKLR1). Chemerin has been studied in various lung disease models, showing both pro- and anti-inflammatory properties. Given the incidence and burden of inflammatory lung diseases from diverse origins (infectious, autoimmune, age-related, etc.), chemerin has emerged as an interesting therapeutical target due to its immunomodulatory role. However, as highlighted by this review, further research efforts to elucidate the mechanisms governing chemerin's dual pro- and anti-inflammatory characteristics are urgently needed. Moreover, although a growing body of evidence suggests chemerin as a potential biomarker for the diagnosis and/or prognosis of inflammatory lung diseases, this review underscores the necessity for standardizing both sampling types and measurement techniques before drawing definitive conclusions. [ABSTRACT FROM AUTHOR]

Background: Inflammatory response has been recognized as a pivotal pathophysiological process during cerebral ischemia. ChemR23 signaling is involved in the pathophysiology of various inflammatory diseases. Nevertheless, the role of ChemR23 signaling in ischemic stroke remains largely unknown. Methods: Permanent ischemic stroke mouse model was accomplished by middle cerebral artery occlusion (MCAO). Resolvin E1 (RvE1) or chemerin-9 (C-9), the agonists of ChemR23, were administered by intracerebroventricular (i.c.v) injection before MCAO induction. Then, analysis of neurobehavioral deficits and brain sampling were done at Day 1 after MCAO. The brain samples were further analyzed by histological staining, immunofluorescence, RNA sequencing, ELISA, transmission electron microscope, and western blots. Furthermore, oxygen–glucose deprivation (OGD) was employed in SH-SY5Y to mimic MCAO in vitro, and ChemR23 signaling pathway was further studied by overexpression of ChemR23 or administration of related agonists or antagonists. Analysis of cell death and related pathway markers were performed. Results: ChemR23 expression was upregulated following MCAO. Under in vitro and in vivo ischemic conditions, ChemR23 deficiency or inhibition contributed to excessive NLRP3-mediated maturation and release of IL-1β and IL-18, as well as enhanced cleavage of GSDMD-N and neuronal pyroptosis. These influences ultimately aggravated brain injury and neuronal damage. On the other hand, ChemR23 activation by RvE1 or C-9 mitigated the above pathophysiological abnormalities in vivo and in vitro, and overexpression of ChemR23 in SH-SY5Y cells also rescued OGD-induced neuronal pyroptosis. Blockade of NLRP3 mimics the protective effects of ChemR23 activation in vitro. Conclusion: Our data indicated that ChemR23 modulates NLRP3 inflammasome-mediated neuronal pyroptosis in ischemic stroke. Activation of ChemR23 may serve as a promising potential target for neuroprotection in cerebral ischemia. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus (GDM) is one of the most common medical disorders in pregnancy. Adipokines, predominantly secreted by adipose tissue, are involved in numerous metabolic processes. The exact role of adipokines in the pathogenesis of GDM is still not well known, and numerous adipokines have been analysed throughout pregnancy and proposed as biomarkers of GDM. This study aimed to evaluate serum adiponectin, chemerin, lipocalin and apelin levels in GDM and non-GDM women, to assess them as clinically useful biomarkers of the occurrence of GDM and to demonstrate the correlation between the levels of the above adipokines in the blood serum and the increased risk of the development of GDM. The role of these adipokines in the pathogenesis of GDM was also analysed. The statistically significant differences between the levels of adiponectin (7234.6 vs. 9837.5 ng/mL, p < 0.0001), chemerin (264.0 vs. 206.7 ng/mL, p < 0.0001) and lipocalin (39.5 vs. 19.4 ng/mL, p < 0.0001) were observed between pregnant women with GDM and healthy ones. The diagnostic usefulness of the tested adipokines in detecting GDM was also assessed. The research results confirm the hypothesis on the significance of adiponectin, chemerin, lipocalin and apelin in the pathophysiological mechanisms of GDM. We speculate that these adipokines could potentially be established as novel biomarkers for the prediction and early diagnosis of GDM. [ABSTRACT FROM AUTHOR]

Angiopoietin-like proteins (ANGPTLs) mediate many metabolic functions. We had recently reported increased plasma levels of ANGPTL8 in obese adults of Arab ethnicity. However, data on ANGPTL8 levels in adolescent obesity is lacking. Arab population is characterized by a rapid transition, due to sudden wealth seen in the post-oil era, in lifestyle, food habits and extent of physical activity. We adopted a cross-sectional study on Arab adolescents from Kuwait to examine the role of ANGPTL8 in adolescent obesity. The study cohort included 452 adolescents, aged 11-14 years, recruited from Middle Schools across Kuwait. BMI-for-age growth charts were used to categorize adolescents as normalweight, overweight, and obese. ELISA and bead-based multiplexing assays were used to measure plasma levels of ANGPTL8 and other inflammation and obesity-related biomarkers. Data analysis showed significant differences in the plasma levels of ANGPTL8 among the three subgroups, with a significant increase in overweight and obese children compared to normal-weight children. This observation persisted even when the analysis was stratified by sex. Multinomial logistic regression analysis illustrated that adolescents with higher levels of ANGPTL8 were 7 times more likely to become obese and twice as likely to be overweight. ANGPTL8 levels were correlated with those of hsCRP, leptin and chemerin. ANGPTL8 level had a reasonable prognostic power for obesity with an AUC of 0.703 (95%-CI=0.648-0.759). These observations relating to increased ANGPTL8 levels corresponding to increased BMI-for-age z-scores indicate that ANGPTL8, along with hsCRP, leptin and chemerin, could play a role in the early stages of obesity development in children. ANGPTL8 is a potential early marker for adolescent obesity and is associated with well-known obesity and inflammatory markers. [ABSTRACT FROM AUTHOR]

Visfatin, as a novel adipokine, is considered to play a role in periodontal inflammation. Chemerin is another newly identified adipokine that is possible to have a role in periodontitis firstly reported in our previous study. The aim of the current study is to evaluate the gingival crevicular fluid (GCF) levels of visfatin and chemerin in periodontitis and and compare these adipokine levels with before and after non-surgical periodontal treatment. Twenty-nine patients with Stage III Grade B periodontitis and eighteen healthy subjects included in this cross-sectional cohort study. Clinical periodontal parameters and GCF were obtained from all subjects. Eight weeks after the following non-surgical periodontal treatment including scaling and root planning, samples and clinical periodontal parameters were collected again in the periodontitis group. The levels of adipokines were analyzed with standard enzyme-linked immunosorbent assay. The levels of visfatin and chemerin were statistically significantly higher at periodontitis group as compared to healthy group (P < 0.001). Although, no changes were observed in visfatin levels after periodontal treatment (P > 0.05), chemerin levels were significantly decreased (P < 0.001). Also, no differences were observed as compared to the healthy group (P > 0.05). Visfatin and chemerin may play a role in the periodontal disease process. In addition, it can be considered that the decreased chemerin levels after non-surgical periodontal treatment may play an important role for developing host modulation strategies. [ABSTRACT FROM AUTHOR]

Obesity is a well-established risk factor for various malignancies and emerging evidence suggests that adipokines play a pivotal role in linking excess adiposity to tumorigenesis. Adipokines are bioactive molecules secreted by adipose tissue and their altered expression in obesity contributes to a pro-inflammatory, pro-angiogenic, and growth-promoting microenvironment conducive to tumorigenesis. Leptin, a key adipokine, activates survival and proliferative signaling pathways whereas adiponectin exhibits tumor-suppressive effects by inducing apoptosis and cell cycle arrest. Visfatin has also been documented to promote tumor growth, angiogenesis, migration, and invasion. Moreover, emerging studies suggest that adipokines, such as resistin, apelin, and chemerin, which are overexpressed in obesity, may also possess oncogenic functions. Despite advancements in our understanding of the roles of individual adipokines in cancer, the intricate interplay and crosstalk between adipokines, tumor cells, and the tumor microenvironment remain complex and multifaceted. This review highlights the evolving knowledge of how adipokines contribute to obesity-related tumorigenesis, shedding light on the potential of targeting adipokine signaling pathways as a novel therapeutic approach for obesity-associated cancers. Further research on the specific mechanisms and interactions between adipokines and tumor cells is crucial for a comprehensive understanding of obesity-associated cancer pathogenesis. [ABSTRACT FROM AUTHOR]

The pleiotropic chemokine chemerin is involved in multiple processes in metabolism and inflammation. The present study aimed to elucidate its regulation in morbid obesity and during therapy-induced rapid weight loss. A total of 128 severely obese patients were enrolled, and their basal anthropometric and clinical parameters were assessed. In total, 64 individuals attended a conservative 12-month weight loss program that included a low calorie-formula diet (LCD), and 64 patients underwent bariatric surgery (Roux-en-Y gastric bypass, RYGB). Blood serum was obtained at study baseline and at follow-up visits after 3, 6, and 12 months. Systemic chemerin concentrations, as well as metabolic and immunological parameters, were quantified. During the 12-month period studied, serum chemerin levels decreased significantly with weight loss after bariatric surgery, as well as with conservative low calorie therapy; however, the effects of RYGB were generally stronger. No substantial associations of systemic chemerin concentrations with therapy-induced improvement of type 2 diabetes and with indicators of liver function and fibrosis were observed. We conclude that systemic chemerin levels decrease in obese individuals during weight loss, regardless of the therapeutic strategy. A potential involvement in weight loss-associated improvement of metabolic disorders and liver fibrosis remains to be further investigated. [ABSTRACT FROM AUTHOR]

Objectives: Chemerin, as a novel multifunctional adipokine, is proposed to be involved in high cancer risk and mortality. The present study was aimed to evaluate the prognostic value of serum Chemerin and neutrophils in patients with oral squamous cell carcinoma (OSCC). Materials and methods: 120 patients with OSCC were included in this prospective cohort study. The levels of serum Chemerin were measured by enzyme-linked immunosorbent assay (ELISA). We also explored the possible effects of Chemerin on neutrophils’ chemokines in OSCC using a real-time PCR, western blotting. Results: Levels of serum Chemerin, neutrophils and NLR were significantly higher among non-survivors compared to survivors of OSCC (both P

Although some cohort studies have indicated a close association between diabetes and HCC, the underlying mechanism about the contribution of diabetes to HCC progression remains largely unknown. In the study, we applied a novel HCC model in SD rat with diabetes and a series of high glucose-stimulated cell experiments to explore the effect of a high glucose environment on HCC metastasis and its relevant mechanism. Our results uncovered a novel regulatory mechanism by which nuclear translocation of metabolic enzyme PKM2 mediated high glucose-promoted HCC metastasis. Specifically, high glucose-increased PKM2 nuclear translocation downregulates chemerin expression through the redox protein TRX1, and then strengthens immunosuppressive environment to promote HCC metastasis. To the best of our knowledge, this is the first report to elucidate the great contribution of a high glucose environment to HCC metastasis from a new perspective of enhancing the immunosuppressive microenvironment. Simultaneously, this work also highlights a previously unidentified non-metabolic role of PKM2 and opens a novel avenue for cross research and intervention for individuals with HCC and comorbid diabetes.

The prevalence of osteoporosis has been on the rise globally. With ageing populations, research has sought therapeutic solutions in novel areas. One such area is that of the adipokines. Current literature points to an important role for these chemical mediators in relation to bone metabolism. Well-established adipokines have been broadly reported upon. These include adiponectin and leptin. However, other novel adipokines such as visfatin, nesfatin-1, meteorin-like protein (Metrnl), apelin and lipocalin-2 are starting to be addressed pre-clinically and clinically. Adipokines hold pro-inflammatory and anti-inflammatory properties that influence the pathophysiology of various bone diseases. Omentin-1 and vaspin, two novel adipokines, share cardioprotective effects and play essential roles in bone metabolism. Studies have reported bone-protective effects of omentin-1, whilst others report negative associations between omentin-1 and bone mineral density. Lipocalin-2 is linked to poor bone microarchitecture in mice and is even suggested to mediate osteoporosis development from prolonged disuse. Nesfatin-1, an anorexigenic adipokine, has been known to preserve bone density. Animal studies have demonstrated that nesfatin-1 treatment limits bone loss and increases bone strength, suggesting exogenous use as a potential treatment for osteopenic disorders. Pre-clinical studies have shown adipokine apelin to have a role in bone metabolism, mediated by the enhancement of osteoblast genesis and the inhibition of programmed cell death. Although many investigations have reported conflicting findings, sufficient literature supports the notion that adipokines have a significant influence on the metabolism of bone. This review aims at highlighting the role of novel adipokines in osteoporosis while also discussing their potential for treating osteoporosis.

ABSTRACT: The genetic selection progress in layers and broilers makes poultry production one of the fastest growing industries. Objectives of the breeding companies are the stability or the increase in the laying rate and the production of viable chicks. New biomarkers are necessary to improve reproductive and egg performances. Chemerin (Chem) produced by oviduct accumulates in egg white (EW). Here, we hypothesized that EW Chem concentration was dependent on the stage of laying and on the breed (layer vs. broiler). In addition, they could be associated to laying performance and fertility parameters. In breeding companies, we collected during 2 successive generations (G0 (mother) and G1 (daughter)) eggs from 100 layers and 100 broilers hens during 5 d at 3 stages: before, after laying peak and at the end of laying period. For each egg, the EW was sampled to measure Chem concentration by ELISA assay. In each generation at the end of laying period, magnums from oviduct, where the EG is formed, were collected in layers and broilers in order to investigate Chem differential expression by RT-qPCR between both breeds. Chem concentration in EW was dependent on the time of laying period and its profile was differently regulated in layers and broilers. Indeed, it increased at the end of laying in layers whereas it decreased after the laying peak in broilers. At the end of laying period, Chem concentration in EW was almost 2-fold higher in layers than in broilers and this was confirmed in both G0 and G1 generations at the Chem mRNA and protein levels in the magnum. For the 2 successive generations, Chem concentration in EW was negatively correlated with the laying rate and the fertility parameter in broiler hens whereas it was negatively correlated with the egg quality (weight of whole egg and weight of albumen) and positively with the fertility rate at some time of laying in layer hens. Taken together, the Chem concentration in EW could be a potential predictive tool for reproductive parameters in genetic selection.

ABSTRACT: Intensive genetic selection of broiler breeders and layer hens resulted in differences in the mechanisms of growth and also in cell metabolism during embryogenesis. Previous research has shown that an adipokine named chemerin and one of these receptors, CMKLR1 were potentially involved in broiler embryo development. Here, our objectives were 1) to compare the expression of chemerin and its receptors CMKLR1, GPR1, and CCRL2 and chemerin concentration in extra-embryonic annexes (allantoic and amniotic membranes and fluids and plasma) in broiler and layer fertile eggs during the development (embryonic day (ED) 7, 14, and 18) by RT-qPCR and specific chicken ELISA and 2) to investigate the role of chemerin and one of its receptors GPR1 in embryo development after in ovo injections of neutralizing antibodies against chicken chemerin and GPR1. We found that chemerin expression in amniotic membranes was higher in layer than broiler eggs at ED7 and ED14 whereas the expression of the 3 receptors was higher in layer than broiler in the allantoic membranes at ED14 and ED18. Chemerin concentration was more important in layer than broiler at ED14 and ED18 in amniotic liquid and at all the studied stages in blood plasma. We also showed positive correlation between amniotic chemerin concentration and chemerin amniotic membrane expression, chemerin plasma concentration and embryo body weight in both breeds. Finally, in ovo injection of chicken chemerin and GPR1 neutralizing antibodies increased embryo mortality in both layer and broiler eggs. Taken together, even if chemerin concentration and chemerin system expression in embryonic membranes are mainly higher expressed in layer than in broiler, chemerin potentially through GPR1 could promote embryo development in both breeds.

Chemerin acts as both a chemotactic agent and an adipokine that undergoes proteolytic cleavage, converting inactive precursors into their active forms before being subsequently inactivated. Elevated chemerin levels are linked to obesity and type 2 diabetes mellitus (T2D). This study aimed to elucidate the effects of T2D and obesity on chemerin levels by comparing plasma samples from individuals with a normal weight and T2D (BMI < 25; NWD group n = 22) with those from individuals who are overweight or obese and have T2D (BMI ≥ 25; OWD group n = 39). The total chemerin levels were similar in the NWD and OWD groups, suggesting that T2D may equalize the chemerin levels irrespective of obesity status. The cleavage of chemerin has been previously linked to myocardial infarction and stroke in NWD, with potential implications for inflammation and mortality. OWD plasma exhibited lower levels of cleaved chemerin than the NWD group, suggesting less inflammation in the OWD group. Here, we showed that the interaction between obesity and T2D leads to an equalization in the total chemerin levels. The cleaved chemerin levels and the associated inflammatory state, however, differ significantly, underscoring the complex relationship between chemerin, T2D, and obesity.

Chemerin is a chemokine/adipokine, regulating inflammation, adipogenesis and energy metabolism whose activity depends on successive proteolytic cleavages at its C-terminus. Chemerin levels and processing are correlated with insulin resistance. We hypothesized that chemerin processing would be higher in individuals with type 2 diabetes (T2D) and in those who are insulin resistant (IR). This hypothesis was tested by characterizing different chemerin forms by specific ELISA in the plasma of 18 participants with T2D and 116 without T2D who also had their insulin resistance measured by steady-state plasma glucose (SSPG) concentration during an insulin suppression test. This approach enabled us to analyze the association of chemerin levels with a direct measure of insulin resistance (SSPG concentration). Participants were divided into groups based on their degree of insulin resistance using SSPG concentration tertiles: insulin sensitive (IS, SSPG ≤ 91 mg/dL), intermediate IR (IM, SSPG 92–199 mg/dL), and IR (SSPG ≥ 200 mg/dL). Levels of different chemerin forms were highest in patients with T2D, second highest in individuals without T2D who were IR, and lowest in persons without T2D who were IM or IS. In the whole group, chemerin levels positively correlated with both degree of insulin resistance (SSPG concentration) and adiposity (BMI). Participants with T2D and those without T2D who were IR had the most proteolytic processing of chemerin, resulting in higher levels of both cleaved and degraded chemerin. This suggests that increased inflammation in individuals who have T2D or are IR causes more chemerin processing.

Adipose tissue is an active endocrine gland, synthesizing and secreting multiple signaling molecules termed adipokines. Following the detection of adipokines and their receptors in the mammary tissue of various species, it is indicated that adipokines play a role in the development of the mammary gland. The aim of the present study was to determine the concentration-dependent influence of three adipokines, leptin, adiponectin, and chemerin, on the viability, apoptosis, and secretory activity of BME-UV1 bovine mammary epithelial cells. The study confirmed that BME-UV1 cells contain the leptin receptor (Ob-R) protein, and express transcripts of adiponectin (ADIPOR1 and ADIPOR2) and chemerin (CMLKR1 and GPR1) receptors. Regardless of the administered dose, none of the three tested adipokines had an effect on the viability of BME-UV1 cells, and the number of apoptotic cells remained unchanged. However, chemerin (100 ng/mL) stimulated BME-UV1 cells to synthesize and secrete αS1-casein, the major protein component of milk. These results indicate that chemerin may be a potent regulator of the bovine mammary epithelial cells’ functional differentiation, contributing, along with the major systemic hormones and local growth factors, to the development of the bovine mammary gland.

Recruitment and accumulation of reactive astrocytes around senile plaques are common pathological features of Alzheimer’s disease (AD), with unclear mechanisms. Chemerin, an adipokine implicated in neuroinflammation, acts through its receptor, chemokine-like receptor 1 (CMKLR1), which also functions as a receptor for amyloid β (Aβ). The impact of the chemerin/CMKLR1 axis on astrocyte migration towards Aβ plaques is unknown. Here we investigated the effect of CMKLR1 on astrocyte migration around Aβ deposition in APP/PS1 mice with Cmklr1 knockout (APP/PS1-Cmklr1−/−). CMKLR1-expressed astrocytes were upregulated in the cortices and hippocampi of 9-month-old APP/PS1 mice. Chemerin mainly co-localized with neurons, and its expression was reduced in the brains of APP/PS1 mice, compared to WT mice. CMKLR1 deficiency decreased astrocyte colocalization with Aβ plaques in APP/PS1-Cmklr1−/− mice, compared to APP/PS1 mice. Activation of the chemerin/CMKLR1 axis promoted the migration of primary cultured astrocytes and U251 cells, and reduced astrocyte clustering induced by Aβ42. Mechanistic studies revealed that chemerin/CMKLR1 activation induced STING phosphorylation. Deletion of STING attenuated the promotion of the chemerin/CMKLR1 axis relative to astrocyte migration and abolished the inhibitory effect of chemerin on Aβ42-induced astrocyte clustering. These findings suggest the involvement of the chemerin/CMKLR1/STING pathway in the regulation of astrocyte migration and recruitment to Aβ plaques/Aβ42.

Chemerin is an atypical chemokine first described as a chemoattractant agent for monocytes, natural killer cells, plasmacytoid and myeloid dendritic cells, through interaction with its main receptor, the G protein-coupled receptor chemokine-like receptor 1 (CMKLR1). Chemerin has been studied in various lung disease models, showing both pro- and anti-inflammatory properties. Given the incidence and burden of inflammatory lung diseases from diverse origins (infectious, autoimmune, age-related, etc.), chemerin has emerged as an interesting therapeutical target due to its immunomodulatory role. However, as highlighted by this review, further research efforts to elucidate the mechanisms governing chemerin’s dual pro- and anti-inflammatory characteristics are urgently needed. Moreover, although a growing body of evidence suggests chemerin as a potential biomarker for the diagnosis and/or prognosis of inflammatory lung diseases, this review underscores the necessity for standardizing both sampling types and measurement techniques before drawing definitive conclusions.

• Chemerin knockdown exacerbated HFD-induced weight gain, fat accumulation (especially in sWAT) and inhibited WAT browning, but improved blood lipid in aged mice. • Exercise-regulated improvements of blood lipid, as well as the distribution and browning of WAT were abrogated by chemerin knockdown. • Chemerin's role in regulating the distribution and browning of WAT associated with the changes of adiponectin, leptin and adiponectin/leptin ratio in serum and WAT. • Exercise-induced beneficial changes in adiponectin, leptin and adiponectin/leptin ratio were blocked by chemerin knockdown. With aging, white adipose tissue (WAT) undergoes distribution change and browning inhibition, which could be attenuated by exercise. Adipokine chemerin exerts roles in the above changes of WAT, and our previous studies demonstrated the effect of decreased chemerin on exercise-induced improvement of glucose and lipid metabolism in high fat diet (HFD) feeding male mice, so this study is to clarify whether chemerin's effects on glucose and lipid metabolism are associated with the distribution and browning of WAT. After diet and exercise interventions, body weight and adipose tissue contents in different depots of male mice were weighed, body composition and energy metabolism parameters were determined by Echo MRI Body Composition Analyzer and metabolic cage, respectively. The levels of serum adiponectin and leptin were detected by ELISA, and the protein levels of PGC-1α, UCP1, adiponectin and leptin in WAT were measured by Western blot. Chemerin knockout exacerbated HFD-induced weight gain, upregulated the increases of visceral and subcutaneous WAT (vWAT and sWAT, especial in sWAT), and inhibited WAT browning, but improved blood lipid. Exercise reduced the body weight and WAT distribution, increased sWAT browning and further improved blood lipid in aged HFD male mice, which were abrogated by chemerin knockout. Detrimental alterations of leptin, adiponectin and adiponectin/leptin ratio were discovered in the serum and WAT of aged HFD chemerin(-/-) mice; and exercise-induced beneficial changes in these adipokines were blocked by chemerin knockout. Chemerin influences blood lipid of aged male mice under HFD and exercise states through regulating the distribution and browning of WAT, which might be related to the changes of adiponectin, leptin and adiponectin/leptin ratio. [ABSTRACT FROM AUTHOR]

Embryonic mortality is a significant problem in the commercial duck industry worldwide. Therefore, identification of new biomarkers for duck embryo development is necessary. In the chicken (order Galliformes), we previously showed that chemerin is a hormone locally produced by the reproductive tract in hens, particularly in the magnum area, leading to its accumulation in the egg white and within the embryo annexes during embryonic development. We therefore hypothesized that the chemerin concentration in egg white could be a biomarker of egg performance and reproductive parameters in Pekin ducks (order Anseriformes). Thus, we collected eggs from Pekin ducks over a 5-d period at three stages of the laying period (before the laying peak, after the laying peak, and at the end of the laying period) to measure the chemerin concentrations in egg white by enzyme-linked immunosorbent assay. The chemerin concentration in egg white decreased during the laying period and was not associated with reproductive parameters. We found negative correlations between the chemerin level in egg white and the albumen weight. Reverse-transcriptase quantitative polymerase chain reaction showed that chemerin and its three receptors CMKLR1, GPR1, and CCRL2 were expressed in the reproductive tract and within allantoic and amniotic annexes during embryo development. Chemerin concentrations strongly increased in amniotic fluid on embryonic day 16 (ED16) when the egg white was transferred into the amniotic sac. Finally, chemerin inhibition in egg white by in ovo injections of anti-chemerin antibodies (0.01, 0.1, and 1 µg) increased the embryo mortality rate. These data demonstrate the important role of the chemerin system during egg formation and embryo development in Pekin ducks, suggesting their potential use as biomarkers for determining the quality of poultry eggs and embryo development. [ABSTRACT FROM AUTHOR]

In this observational cross-sectional study, we investigated the relationship between combined obesogenic neighbourhood characteristics and various cardiovascular disease risk factors in adults, including BMI, systolic blood pressure, and blood lipids, as well as the prevalence of overweight/obesity, hypertension, and dyslipidaemia. We conducted a large-scale pooled analysis, comprising data from five Dutch cohort studies (n = 183,871). Neighbourhood obesogenicity was defined according to the Obesogenic Built-environmental CharacterisTics (OBCT) index. The index was calculated for 1000m circular buffers around participants' home addresses. For each cohort, the association between the OBCT index and prevalence of overweight/obesity, hypertension and dyslipidaemia was analysed using robust Poisson regression models. Associations with continuous measures of BMI, systolic blood pressure, LDL-cholesterol, HDL-cholesterol, and triglycerides were analysed using linear regression. All models were adjusted for age, sex, education level and area-level socio-economic status. Cohort-specific estimates were pooled using random-effects meta-analyses. The pooled results show that a 10 point higher OBCT index score was significantly associated with a 0.17 higher BMI (95%CI: 0.10 to 0.24), a 0.01 higher LDL-cholesterol (95% CI: 0.01 to 0.02), a 0.01 lower HDL cholesterol (95% CI: −0.02 to −0.01), and non-significantly associated with a 0.36 mmHg higher systolic blood pressure (95%CI: −0.14 to 0.65). A 10 point higher OBCT index score was also associated with a higher prevalence of overweight/obesity (PR = 1.03; 95% CI: 1.02 to 1.05), obesity (PR = 1.04; 95% CI: 1.01 to 1.08) and hypertension (PR = 1.02; 95% CI: 1.00 to 1.04), but not with dyslipidaemia. This large-scale pooled analysis of five Dutch cohort studies shows that higher neighbourhood obesogenicity, as measured by the OBCT index, was associated with higher BMI, higher prevalence of overweight/obesity, obesity, and hypertension. These findings highlight the importance of considering the obesogenic environment as a potential determinant of cardiovascular health. • Our study adds value to the existing evidence by considering combined exposure to obesogenic environmental factors. • We used the Obesogenic Built-environmental CharacterisTics (OBCT) index to combine various exposures based on theory and evidence. • We found that a higher OBCT index score is associated with higher BMI, prevalence of overweight/obesity, and hypertension. • The results also show minimal associations with blood lipids, and a potential relationship with systolic blood pressure. • This study highlights the potential use of the OBCT index in identifying areas at risk for CVD risk factors. [ABSTRACT FROM AUTHOR]