The Role of Chemerin in Human Disease2nd Edition

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: 31 August 2025 | Viewed by 12408

Special Issue Editor

Special Issue Information

Dear Colleagues,

This Special Issue, entitled “The Role of Chemerin in Human Disease”, will focus on the selection of recent research topics and up-to-date review articles focusing on the role of chemerin in disease.

Chemerin is a well-characterized adipokine which has multiple functions. Adipose tissue and serum levels are increased in the obese, and chemerin plays a significant role in adipogenesis and glucose homeostasis. The C-terminal processing of chemerin generates biologically active isoforms and, moreover, contributes to chemerin inactivation. Different chemerin isoforms have been identified, but their particular physiological functions remain mostly unknown. Chemerin isoform tissue distribution, signalling pathways, and biological activities require further investigation.

There is emerging evidence that chemerin is an important molecule in various cancers. Leukocyte recruitment via this chemoattractant mostly leads to the suppression of tumor growth, while chemerin-induced angiogenesis is one of its tumor-promoting activities. Chemerin has already been described as a major factor in various diseases, such as coronary artery disease, hypertension, Alzheimer´s disease, and chronic obstructive pulmonary disease.

With this Special Issue of Biomedicines, we aim to collect articles which clarify the pathophysiological role of chemerin in human diseases. Articles investigating chemerin’s role as a biomarker in human diseases are also welcome. Moreover, we invite authors to write review articles providing a comprehensive and critical overview of the current literature.

Prof. Dr. Christa Buechler
Guest Editor

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Keywords

  • biomarker
  • chemotaxis
  • cardiovascular diseases
  • cancer
  • chemerin isoforms
  • CMKLR1
  • GPR1
  • CCRL2

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Published Papers (7 papers)

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Research

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22 pages, 4129 KiB  
Article
Active Forms of Chemerin Are Elevated in Human and Mouse Ovarian Carcinoma
by Lei Zhao, Qin Zhou, Venkatesh Krishnan, Justine Chan, Simone Sasse, Supreeti Tallapragada, Dan Eisenberg, Lawrence Leung, Oliver Dorigo and John Morser
Biomedicines 2025, 13(4), 991; https://doi.org/10.3390/biomedicines13040991 - 18 Apr 2025
Viewed by 224
Abstract
Background: Chemerin is a small adipokine that is activated and inactivated by proteolysis of its C-terminus with a role in regulating metabolism, immunity, and inflammation. Significant levels of chemerin are found in circulation and ascitic fluid of ovarian carcinoma patients. Methods: We investigated [...] Read more.
Background: Chemerin is a small adipokine that is activated and inactivated by proteolysis of its C-terminus with a role in regulating metabolism, immunity, and inflammation. Significant levels of chemerin are found in circulation and ascitic fluid of ovarian carcinoma patients. Methods: We investigated the levels of different chemerin forms in three cohorts: people with BMI < 25, with BMI > 40, and ovarian carcinoma ascites with ELISAs specific for different chemerin forms. Ascites from a mouse model of ovarian carcinoma were also analyzed, and the model was compared between wild-type and chemerin-deficient mice. Results: Conversion of plasma to serum increased the levels of processed chemerin with lower increases in samples from people with BMI < 25 than in people with BMI > 40. High levels of total chemerin and processed forms of chemerin were found in ascitic fluid from both patients who had a mean BMI of 29 and the mouse model. In chemerin-deficient mice the tumors grew slower than in wild-type mice. Conclusions: Serum has more processed and active chemerin than plasma irrespective of source. Ascites of ovarian carcinoma patients contained high levels of active chemerin, which, based on the mouse data, enhance tumor growth. Full article
(This article belongs to the Special Issue The Role of Chemerin in Human Disease2nd Edition)
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16 pages, 4153 KiB  
Article
Metabolic Activity in Human Intermuscular Adipose Tissue Directs the Response of Resident PPARγ+ Macrophages to Fatty Acids
by Xiaoying Chen, Sebastian Ludger Schubert, Aline Müller, Miguel Pishnamaz, Frank Hildebrand and Mahtab Nourbakhsh
Biomedicines 2025, 13(1), 10; https://doi.org/10.3390/biomedicines13010010 - 25 Dec 2024
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Abstract
Background/Objectives: Peroxisome proliferator-activated receptor gamma (PPARγ) is a fatty acid-binding transcription activator of the adipokine chemerin. The key role of PPARγ in adipogenesis was established by reports on adipose tissue-resident macrophages that express PPARγ. The present study examined PPARγ+ macrophages in [...] Read more.
Background/Objectives: Peroxisome proliferator-activated receptor gamma (PPARγ) is a fatty acid-binding transcription activator of the adipokine chemerin. The key role of PPARγ in adipogenesis was established by reports on adipose tissue-resident macrophages that express PPARγ. The present study examined PPARγ+ macrophages in human skeletal muscle tissues, their response to fatty acid (FA) species, and their correlations with age, obesity, adipokine expression, and an abundance of other macrophage phenotypes. Methods: An ex vivo human skeletal muscle model with surgical specimens that were maintained without or with FAs for up to 11 days was utilized. Immunofluorescence analysis was used to detect macrophage phenotypes and mitochondrial activity. Preconfigured arrays were used to detect the expression of 34 different adipokines and chemokines. Results: Data from 14 adults revealed that PPARγ+ macrophages exclusively reside in intermuscular adipose tissue (IMAT), and their abundance correlates with the metabolic status of surrounding adipocytes during tissue maintenance in vitro for 9–11 days. Elevated fatty acid levels lead to significant increases in PPARγ+ populations, which are correlated with the donor’s body mass index (BMI). Conclusions: PPARγ+ macrophages represent a distinctly specialized population of regulatory cells that reside within human IMATs in accordance with their metabolic status. Thus, future in-depth studies on IMAT-resident PPARγ+ macrophage action mechanisms will elucidate the role of skeletal muscle in the pathogenesis of human metabolic dysfunction. Full article
(This article belongs to the Special Issue The Role of Chemerin in Human Disease2nd Edition)
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17 pages, 2470 KiB  
Article
A Cross-Sectional Study: Systematic Quantification of Chemerin in Human Cerebrospinal Fluid
by Alexandra Höpfinger, Manuel Behrendt, Andreas Schmid, Thomas Karrasch, Andreas Schäffler and Martin Berghoff
Biomedicines 2024, 12(11), 2508; https://doi.org/10.3390/biomedicines12112508 - 1 Nov 2024
Cited by 2 | Viewed by 1116
Abstract
Background: Dysregulation of adipokines is considered a key mechanism of chronic inflammation in metabolic syndrome. Some adipokines affect food intake by crossing the blood/brain barrier. The adipokine chemerin is associated with metabolic syndrome, cardiovascular diseases and immune response. Little is known about chemerin’s [...] Read more.
Background: Dysregulation of adipokines is considered a key mechanism of chronic inflammation in metabolic syndrome. Some adipokines affect food intake by crossing the blood/brain barrier. The adipokine chemerin is associated with metabolic syndrome, cardiovascular diseases and immune response. Little is known about chemerin’s presence in cerebrospinal fluid (CSF) and its ability to cross the blood/CSF barrier. Methods: We quantified chemerin levels in paired serum and CSF samples of 390 patients with different neurological diagnoses via enzyme-linked immunosorbent assay (ELISA). Correlation analyses of serum and CSF chemerin levels with anthropometric, serum and CSF routine parameters were performed. Results: Overweight patients exhibited higher chemerin levels in serum and CSF. Chemerin CSF levels were higher in men. Chemerin levels in serum were associated with BMI (body mass index) and CRP (C-reactive protein). Chemerin levels in CSF were associated with age. Neurological diseases affected chemerin levels in CSF. The chemerin CSF/serum ratio was calculated as 96.3 ± 36.8 × 10−3 for the first time. Conclusions: Our data present a basis for the development of standard values for chemerin quantities in CSF. CSF chemerin levels are differentially regulated in neurological diseases and affected by BMI and sex. Chemerin is able to cross the blood/CSF barrier under physiological and pathophysiological conditions. Full article
(This article belongs to the Special Issue The Role of Chemerin in Human Disease2nd Edition)
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13 pages, 1486 KiB  
Article
Chemerin Levels in COVID-19 Are More Affected by Underlying Diseases than by the Virus Infection Itself
by Vlad Pavel, Pablo Amend, Niklas Schmidtner, Alexander Utrata, Charlotte Birner, Stephan Schmid, Sabrina Krautbauer, Martina Müller, Patricia Mester and Christa Buechler
Biomedicines 2024, 12(9), 2099; https://doi.org/10.3390/biomedicines12092099 - 14 Sep 2024
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Abstract
Background/Objectives: Chemerin is an adipokine involved in inflammatory and metabolic diseases, and its circulating levels have been associated with inflammatory parameters in various patient cohorts. Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, which causes COVID-19, triggers inflammatory pathways. However, the association [...] Read more.
Background/Objectives: Chemerin is an adipokine involved in inflammatory and metabolic diseases, and its circulating levels have been associated with inflammatory parameters in various patient cohorts. Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, which causes COVID-19, triggers inflammatory pathways. However, the association between serum chemerin levels and COVID-19 disease severity and outcomes has not been definitively established. Methods: In this study, serum chemerin levels were analyzed in 64 patients with moderate COVID-19 and 60 patients with severe disease. Results: The results showed that serum chemerin levels were comparable between these two groups and slightly higher than in healthy controls. Notably, COVID-19 patients with hypertension exhibited elevated serum chemerin levels, while those with liver cirrhosis had lower levels. When patients with these comorbidities were excluded from the analyses, serum chemerin levels in COVID-19 patients were similar to those in healthy controls. Positive correlations were observed between serum chemerin levels and markers such as alkaline phosphatase, C-reactive protein, eosinophils, and lymphocytes in the entire cohort, as well as in the subgroup excluding patients with hypertension and cirrhosis. Additionally, urinary chemerin levels were comparable between COVID-19 patients and controls, and neither hypertension nor dialysis significantly affected urinary chemerin levels. Both survivors and non-survivors had similar serum and urinary chemerin levels. Conclusions: In conclusion, this study suggests that comorbidities such as arterial hypertension and liver cirrhosis do have a more significant impact on serum chemerin levels than SARS-CoV-2 infection itself. Full article
(This article belongs to the Special Issue The Role of Chemerin in Human Disease2nd Edition)
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Review

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29 pages, 673 KiB  
Review
Chemerin and Polycystic Ovary Syndrome: A Comprehensive Review of Its Role as a Biomarker and Therapeutic Target
by Stefano Palomba, Giuseppe Seminara, Flavia Costanzi, Donatella Caserta and Antonio Aversa
Biomedicines 2024, 12(12), 2859; https://doi.org/10.3390/biomedicines12122859 - 16 Dec 2024
Cited by 1 | Viewed by 1383
Abstract
Background: Chemerin, an adipokine implicated in inflammatory, metabolic, and adipogenic processes, has been detected in high serum concentration in women with polycystic ovary syndrome (PCOS) and seems to play a role in PCOS pathogenesis. Moreover, at present, no comprehensive and critical document is [...] Read more.
Background: Chemerin, an adipokine implicated in inflammatory, metabolic, and adipogenic processes, has been detected in high serum concentration in women with polycystic ovary syndrome (PCOS) and seems to play a role in PCOS pathogenesis. Moreover, at present, no comprehensive and critical document is available in the literature on this topic. The aim of the current study was to comprehensively review the latest available data to confirm the evidence about the association between chemerin and PCOS, highlighting its potential role as an upcoming biomarker and therapeutic target. Methods: A search in the literature of studies published between 2019 and 2024 was conducted using PubMed, Cochrane Library, and Web of Science, focusing on research related to chemerin, PCOS, and PCOS-related features, comorbidities, and complications. A qualitative structured synthesis of key findings was performed according to the specific thematic areas selected, including and discussing clinical data on women with PCOS and experimental studies in humans and animal models of PCOS. Results: Available data confirm increased serum levels of chemerin in women with PCOS compared with controls, independent of obesity and body mass index. Chemerin is associated with insulin resistance, hyperandrogenism, and ovarian dysfunction in PCOS individuals, inhibiting folliculogenesis and steroidogenesis. Experimental animal models underscore chemerin’s regulatory roles through its receptors within the hypothalamic–pituitary–ovarian axis and peripheral tissues. High systemic levels of chemerin in PCOS may also be related to the increased risk of pregnancy complications, especially gestational diabetes mellitus and preeclampsia. Conclusions: The current review study highlights the role of chemerin in PCOS pathophysiology, severity, and associated comorbidities and complications, assessing its value as a future biomarker and foreshadowing its potential as a therapeutic target. Full article
(This article belongs to the Special Issue The Role of Chemerin in Human Disease2nd Edition)
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17 pages, 3415 KiB  
Review
Structural Basis for Chemerin Recognition and Signaling Through Its Receptors
by Yezhou Liu, Aijun Liu and Richard D. Ye
Biomedicines 2024, 12(11), 2470; https://doi.org/10.3390/biomedicines12112470 - 28 Oct 2024
Viewed by 1763
Abstract
Chemerin is a chemotactic adipokine that participates in a multitude of physiological processes, including adipogenesis, leukocyte chemotaxis, and neuroinflammation. Chemerin exerts biological functions through binding to one or more of its G protein-coupled receptors (GPCRs), namely chemokine-like receptor 1 (CMKLR1), G protein-coupled receptor [...] Read more.
Chemerin is a chemotactic adipokine that participates in a multitude of physiological processes, including adipogenesis, leukocyte chemotaxis, and neuroinflammation. Chemerin exerts biological functions through binding to one or more of its G protein-coupled receptors (GPCRs), namely chemokine-like receptor 1 (CMKLR1), G protein-coupled receptor 1 (GPR1), and CC-motif receptor-like 2 (CCRL2). Of these receptors, CMKLR1 and GPR1 have been confirmed as signaling receptors of chemerin, whereas CCRL2 serves as a chemerin-binding protein without transmembrane signaling. High-resolution structures of two chemerin receptors are now available thanks to recent advancements in structure biology. This review focuses on the structural perspectives of the chemerin receptors with an emphasis on the structure–activity correlation, including key components of the two receptors for ligand recognition and conformational changes induced by chemerin and its derivative peptides for G protein activation. There are also comparisons between the two chemerin receptors and selected GPCRs with peptide ligands for better appreciation of the shared and distinct features of the chemerin receptors in ligand recognition and transmembrane signaling, and in the evolution of this subclass of GPCRs. Full article
(This article belongs to the Special Issue The Role of Chemerin in Human Disease2nd Edition)
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16 pages, 506 KiB  
Review
Chemerin in the Spotlight: Revealing Its Multifaceted Role in Acute Myocardial Infarction
by Andreas Mitsis, Elina Khattab, Michael Myrianthefs, Stergios Tzikas, Nikolaos P. E. Kadoglou, Nikolaos Fragakis, Antonios Ziakas and George Kassimis
Biomedicines 2024, 12(9), 2133; https://doi.org/10.3390/biomedicines12092133 - 20 Sep 2024
Cited by 2 | Viewed by 1418
Abstract
Chemerin, an adipokine known for its role in adipogenesis and inflammation, has emerged as a significant biomarker in cardiovascular diseases, including acute myocardial infarction (AMI). Recent studies have highlighted chemerin’s involvement in the pathophysiological processes of coronary artery disease (CAD), where it modulates [...] Read more.
Chemerin, an adipokine known for its role in adipogenesis and inflammation, has emerged as a significant biomarker in cardiovascular diseases, including acute myocardial infarction (AMI). Recent studies have highlighted chemerin’s involvement in the pathophysiological processes of coronary artery disease (CAD), where it modulates inflammatory responses, endothelial function, and vascular remodelling. Elevated levels of chemerin have been associated with adverse cardiovascular outcomes, including increased myocardial injury, left ventricular dysfunction, and heightened inflammatory states post-AMI. This manuscript aims to provide a comprehensive review of the current understanding of chemerin’s role in AMI, detailing its molecular mechanisms, clinical implications, and potential as a biomarker for diagnosis and prognosis. Additionally, we explore the therapeutic prospects of targeting chemerin pathways to mitigate myocardial damage and improve clinical outcomes in AMI patients. By synthesizing the latest research findings, this review seeks to elucidate the multifaceted role of chemerin in AMI and its promise as a target for innovative therapeutic strategies. Full article
(This article belongs to the Special Issue The Role of Chemerin in Human Disease2nd Edition)
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