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      Methodological utility of chemerin as a novel biomarker of immunity and metabolism

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          Abstract

          Chemerin is a recently discovered adipokine with inflammatory and metabolic actions relevant for chronic disease development. However, evidence from human research on the role of chemerin in chronic disease risk is still lacking. We assessed the reliability of plasma chemerin concentrations measured on two occasions over a 4-month period in 207 apparently healthy participants. In addition, we explored the cross-sectional associations between chemerin and inflammatory biomarkers using Spearman partial correlation and multivariable linear regression analyses. Intra-individual reproducibility of chemerin measurements was assessed by calculating intraclass correlation coefficients (ICCs) and exploration of Bland–Altman plots. Reliability analyses revealed good reproducibility of chemerin measurements (ICC: 0.72 (95%-CI 0.65, 0.78)). Visual inspection of Bland–Altman plots confirmed that the two time point measurements had a high level of agreement. In correlation analyses, chemerin was positively correlated with adiposity measures (body mass index and waist circumference). In addition, independent of adiposity measures, chemerin was correlated with the biomarkers C-reactive protein, fatty acid-binding protein 4 and progranulin (Rho-s ranging from 0.23 to 0.37). In multivariable linear regression analysis, a combination of correlated factors including body mass index, waist circumference, C-reactive protein, progranulin and fatty acid-binding protein-4 explained 28.0% of chemerin concentrations. These findings demonstrate methodological utility of chemerin concentrations in population-based research setting. Human studies are highly warranted in order to provide further insights into the role of chemerin as a biomarker linking immunity and metabolism in relation to chronic disease risk.

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          Most cited references24

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          Specific Recruitment of Antigen-presenting Cells by Chemerin, a Novel Processed Ligand from Human Inflammatory Fluids

          Dendritic cells (DCs) and macrophages are professional antigen-presenting cells (APCs) that play key roles in both innate and adaptive immunity. ChemR23 is an orphan G protein–coupled receptor related to chemokine receptors, which is expressed specifically in these cell types. Here we present the characterization of chemerin, a novel chemoattractant protein, which acts through ChemR23 and is abundant in a diverse set of human inflammatory fluids. Chemerin is secreted as a precursor of low biological activity, which upon proteolytic cleavage of its COOH-terminal domain, is converted into a potent and highly specific agonist of ChemR23, the chemerin receptor. Activation of chemerin receptor results in intracellular calcium release, inhibition of cAMP accumulation, and phosphorylation of p42–p44 MAP kinases, through the Gi class of heterotrimeric G proteins. Chemerin is structurally and evolutionary related to the cathelicidin precursors (antibacterial peptides), cystatins (cysteine protease inhibitors), and kininogens. Chemerin was shown to promote calcium mobilization and chemotaxis of immature DCs and macrophages in a ChemR23-dependent manner. Therefore, chemerin appears as a potent chemoattractant protein of a novel class, which requires proteolytic activation and is specific for APCs.
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            Chemerin, a novel adipokine that regulates adipogenesis and adipocyte metabolism.

            Obesity is an alarming primary health problem and is an independent risk factor for type II diabetes, cardiovascular diseases, and hypertension. Although the pathologic mechanisms linking obesity with these co-morbidities are most likely multifactorial, increasing evidence indicates that altered secretion of adipose-derived signaling molecules (adipokines; e.g. adiponectin, leptin, and tumor necrosis factor alpha) and local inflammatory responses are contributing factors. Chemerin (RARRES2 or TIG2) is a recently discovered chemoattractant protein that serves as a ligand for the G protein-coupled receptor CMKLR1 (ChemR23 or DEZ) and has a role in adaptive and innate immunity. Here we show an unexpected, high level expression of chemerin and its cognate receptor CMKLR1 in mouse and human adipocytes. Cultured 3T3-L1 adipocytes secrete chemerin protein, which triggers CMKLR1 signaling in adipocytes and other cell types and stimulates chemotaxis of CMKLR1-expressing cells. Adenoviral small hairpin RNA targeted knockdown of chemerin or CMKLR1 expression impairs differentiation of 3T3-L1 cells into adipocytes, reduces the expression of adipocyte genes involved in glucose and lipid homeostasis, and alters metabolic functions in mature adipocytes. We conclude that chemerin is a novel adipose-derived signaling molecule that regulates adipogenesis and adipocyte metabolism.
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              Metabolic functions of FABPs—mechanisms and therapeutic implications

              Intracellular and extracellular interactions with proteins enables the functional and mechanistic diversity of lipids. Fatty acid-binding proteins (FABPs) were originally described as intracellular proteins that can affect lipid fluxes, metabolism and signalling within cells. As the functions of this protein family have been further elucidated, it has become evident that they are critical mediators of metabolism and inflammatory processes, both locally and systemically, and therefore are potential therapeutic targets for immunometabolic diseases. In particular, genetic deficiency and small molecule-mediated inhibition of FABP4 (also known as aP2) and FABP5 can potently improve glucose homeostasis and reduce atherosclerosis in mouse models. Further research has shown that in addition to their intracellular roles, some FABPs are found outside the cells, and FABP4 undergoes regulated, vesicular secretion. The circulating form of FABP4 has crucial hormonal functions in systemic metabolism. In this Review we discuss the roles and regulation of both intracellular and extracellular FABP actions, highlighting new insights that might direct drug discovery efforts and opportunities for management of chronic metabolic diseases.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                July 2017
                07 June 2017
                : 6
                : 5
                : 340-347
                Affiliations
                [1 ]Department of Epidemiology Nutrition, Immunity and Metabolism Start-up Lab, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany
                [2 ]Department of Food Safety Federal Institute for Risk Assessment, Berlin, Germany
                [3 ]Institute for Social Medicine Epidemiology and Health Economics, Charité University Medical Center, Berlin, Germany
                [4 ]Institute of Epidemiology Christian-Albrechts University Kiel, Kiel, Germany
                [5 ]Department for Clinical Chemistry and Pathobiochemistry Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
                [6 ]Department of Molecular Epidemiology German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany
                [7 ]German Center of Diabetes Research (DZD) München-Neuherberg, Germany
                [8 ]Department of Epidemiology German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany
                Author notes
                Correspondence should be addressed to K Aleksandrova; Email: Krasimira.Aleksandrova@ 123456dife.de
                Article
                EC170098
                10.1530/EC-17-0098
                5510453
                28592510
                d12beb15-4afd-48de-9916-97d422e00102
                © 2017 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 1 June 2017
                : 6 June 2017
                Categories
                Research

                adipokine,immune system,reliability,chemerin
                adipokine, immune system, reliability, chemerin

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