+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Chemerin Isoforms and Activity in Obesity


      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Overweight and adiposity are risk factors for several diseases, like type 2 diabetes and cancer. White adipose tissue is a major source for adipokines, comprising a diverse group of proteins exerting various functions. Chemerin is one of these proteins whose systemic levels are increased in obesity. Chemerin is involved in different physiological and pathophysiological processes and it regulates adipogenesis, insulin sensitivity, and immune response, suggesting a vital role in metabolic health. The majority of serum chemerin is biologically inert. Different proteases are involved in the C-terminal processing of chemerin and generate diverse isoforms that vary in their activity. Distribution of chemerin variants was analyzed in adipose tissues and plasma of lean and obese humans and mice. The Tango bioassay, which is suitable to monitor the activation of the beta-arrestin 2 pathway, was used to determine the ex-vivo activation of chemerin receptors by systemic chemerin. Further, the expression of the chemerin receptors was analyzed in adipose tissue, liver, and skeletal muscle. Present investigations assume that increased systemic chemerin in human obesity is not accompanied by higher biologic activity. More research is needed to fully understand the pathways that control chemerin processing and chemerin signaling.

          Related collections

          Most cited references 83

          • Record: found
          • Abstract: found
          • Article: not found

          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.
            • Record: found
            • Abstract: found
            • Article: not found

            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.
              • Record: found
              • Abstract: found
              • Article: not found

              Chemerin: at the crossroads of inflammation and obesity.

              Chemerin is a secreted protein with a complex but well-established role in immune function. Parallel lines of investigation also support the notion that chemerin is a novel adipokine that regulates adipocyte development and metabolic function as well as glucose metabolism in liver and skeletal muscle tissues. A growing body of human experimental data indicates that serum chemerin levels are elevated in patients with obesity and that they exhibit a positive correlation with various aspects of the metabolic syndrome. Thus, the dual role of chemerin in inflammation and metabolism might provide a link between chronic inflammation and obesity, as well as obesity-related disorders such as type 2 diabetes and cardiovascular disease. Copyright © 2010 Elsevier Ltd. All rights reserved.

                Author and article information

                Int J Mol Sci
                Int J Mol Sci
                International Journal of Molecular Sciences
                05 March 2019
                March 2019
                : 20
                : 5
                [1 ]Department of Internal Medicine I, Regensburg University Hospital, 93053 Regensburg, Germany; susanne.feder@ 123456klinik.uni-regensburg.de (S.F.); haberl.elisabeth@ 123456gmx.de (E.M.H.)
                [2 ]Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, 93053 Regensburg, Germany; charalampos.aslanidis@ 123456klinik.uni-regensburg.de
                Author notes
                [* ]Correspondence: christa.buechler@ 123456klinik.uni-regensburg.de ; Tel.: +49-941-944-7009
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).


                Molecular biology

                proteolysis, tango bioassay, biologic activity, chemerin receptors


                Comment on this article