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The Role of Chemerin in Human Disease

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 24014

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Prof. Dr. Christa Buechler

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Department of Internal Medicine I, Regensburg University Hospital, 93053 Regensburg, Germany
Interests: adipose tissue; obesity; sepsis; inflammatory bowel disease; chemerin
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Dear Colleagues,

This Special Issue, “The role of chemerin in human disease”, will focus on the selection of recent research topics and up-to-date review articles related to the role of chemerin in disease.

Chemerin is a well-characterized adipokine with multiple functions. Adipose tissue and serum levels are increased in the obese, and chemerin plays a significant role in adipogenesis and glucose homeostasis. 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 function is mostly unknown. Chemerin isoform tissue distribution, signalling pathways and biological activities are awaiting further investigation.

There is emerging evidence that chemerin is an important molecule in various cancers. Leukocyte recruitment by 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 clarifying the pathophysiological role of chemerin in human diseases. Articles describing chemerin as a biomarker in human diseases are also welcome. Moreover, we invite authors to write review articles to provide a comprehensive and critical overview of the current literature.

Dr. Christa Buechler
Guest Editor

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Keywords

biomarker
chemotaxis
cardiovascular diseases
cancer
chemerin isoforms
CMKLR1
GPR1
CCRL2

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The Role of Chemerin in Human Disease—2nd Edition in Biomedicines (4 articles)

Published Papers (9 papers)

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Research

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12 pages, 4357 KiB

Open AccessArticle

Serum Chemerin Is Decreased by Roux-en-Y Gastric Bypass and Low Calorie-Formula Diet in Obese Individuals

by Andreas Schmid, Martin Roderfeld, Thomas Karrasch, Elke Roeb and Andreas Schäffler

Biomedicines 2024, 12(1), 33; https://doi.org/10.3390/biomedicines12010033 - 22 Dec 2023

Cited by 1 | Viewed by 950

Abstract

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. Full article

(This article belongs to the Special Issue The Role of Chemerin in Human Disease)

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11 pages, 1316 KiB

Open AccessArticle

Plasma Chemerin Is Induced in Critically Ill Patients with Gram-Positive Infections

by Pablo Amend, Patricia Mester, Stephan Schmid, Martina Müller, Christa Buechler and Vlad Pavel

Biomedicines 2023, 11(7), 1779; https://doi.org/10.3390/biomedicines11071779 - 21 Jun 2023

Cited by 4 | Viewed by 1793

Abstract

Chemerin is a chemoattractant protein abundantly expressed in hepatocytes. Chemerin exerts pro- and anti-inflammatory effects and acts as a pro-resolving protein. Chemerin levels are low in patients with liver cirrhosis and are increased in sepsis. The aim of this study was to identify associations between plasma chemerin levels and underlying diseases as well as causes of severe illness. The cohort included 32 patients with liver cirrhosis who had low systemic chemerin, and who were not considered for further evaluation. Plasma chemerin levels were similar between the 27 patients with systemic inflammatory response syndrome (SIRS), the 34 patients with sepsis and the 63 patients with septic shock. Chemerin in plasma correlated with C-reactive protein and leukocyte count but not with procalcitonin, a clinical marker of bacterial infection. Plasma chemerin did not differ among patients with and without ventilation and patients with and without dialysis. Vasopressor therapy was not associated with altered plasma chemerin levels. Infection with severe acute respiratory syndrome coronavirus 2 had no effect on plasma chemerin levels. Baseline levels of plasma chemerin could not discriminate between survivors and non-survivors. Notably, Gram-positive infection was associated with higher chemerin levels. In summary, the current study suggests that plasma chemerin might serve as an early biomarker for the diagnosis of Gram-positive infections in patients with sepsis. Full article

(This article belongs to the Special Issue The Role of Chemerin in Human Disease)

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13 pages, 3678 KiB

Open AccessArticle

Chemerin and Chemokine-like Receptor 1 Expression Are Associated with Hepatocellular Carcinoma Progression in European Patients

by Florian Weber, Kirsten Utpatel, Katja Evert, Oliver Treeck and Christa Buechler

Biomedicines 2023, 11(3), 737; https://doi.org/10.3390/biomedicines11030737 - 1 Mar 2023

Cited by 3 | Viewed by 1854

Abstract

The chemoattractant protein chemerin is protective in experimental hepatocellular carcinoma (HCC), and high expression in HCC tissues of Asian patients was related to a favorable prognosis. Studies from Asia found reduced expression of chemerin in HCC compared to para-tumor tissues while our previous analysis observed the opposite. Aim of this study was to correlate chemerin expression in HCC tissues with disease severity of European patients Hepatocyte chemerin protein expression was assessed by immunohistochemistry in HCC tissue of 383 patients, and was low in 24%, moderate in 49% and high in 27%. High chemerin protein in the HCC tissues was related to the T stage, vessel invasion, histologic grade, Union for International Cancer Control (UICC) stage and tumor size. Chemokine-like receptor 1 (CMKLR1) is a functional chemerin receptor. CMKLR1 protein in hepatocytes was low expressed in HCC tissues of 36%, moderate in tissues of 32% and high in 32% of the HCCs. Tumor CMKLR1 was associated with the T stage, vessel invasion, histologic grade and UICC stage. Notably, sex-specific analysis revealed that associations of chemerin and CMKLR1 expression with HCC progression were significant in males but not in females. The tumor chemerin and CMKLR1 protein expression were not related to steatosis, inflammation and fibrosis grades. In summary, chemerin as well as CMKLR1 protein were related to disease severity of European HCC patients, and this was significant in males. This observation is in contrast to Asian patients where higher chemerin in the tumors was protective. Current analysis provides evidence for ethnicity and sex-related differences of tumor expressed chemerin and HCC severity. Full article

(This article belongs to the Special Issue The Role of Chemerin in Human Disease)

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10 pages, 5112 KiB

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Loss of Chemerin in Rhabdomyosarcoma Cells Polarizes Adjacent Monocytes to an Immunosuppressive Phenotype

by Rui Sun, Jia Le Lin, Man Si Cheng, Kang Yi Lee, Thilo Spruss, Christa Buechler and Herbert Schwarz

Biomedicines 2022, 10(10), 2610; https://doi.org/10.3390/biomedicines10102610 - 18 Oct 2022

Viewed by 1696

Abstract

Chemerin is a multifunctional adipokine that regulates adipogenesis, insulin signaling and blood pressure and has thus a central function in metabolism. Mounting evidence confirmed a function of chemerin in various cancers. In this study, we investigated the role of chemerin in rhabdomyosarcoma (RMS), an aggressive soft tissue cancer that affects mainly children and young adults. We found chemerin expression in 93.8% (90 of 96) of RMS cases, with a range of 86.7–96.7% for the four RMS subgroups. While chemerin is uniformly expressed in normal skeletal muscle, its expression in RMS is patchy with interspersed areas that are devoid of chemerin. This variable chemerin expression is reflected by RMS cell lines as two of them (Rh41 and Rd18) were found to secrete chemerin while the two other ones (JR1 and RD) were negative. Deletion of chemerin in Rh41 and Rd18 cells did not alter their growth rate or morphology. We investigated the potential influence of chemerin on immune surveillance by coculturing parental and chemerin-deficient RMS cells with resting- or lipopolysaccharide (LPS)-activated human peripheral monocytes. The absence of chemerin in the RMS cells led to increased expression levels of the coinhibitory molecules PD-L1 and PD-L2 while levels of the costimulatory molecule CD86 were not changed. Further, the absence of chemerin enhanced the secretion of cytokines (IL-1β, IL-6, IL-10 and TNF) that have been shown to support RMS pathogenesis. These data indicate that the loss of chemerin expression by RMS cells repolarizes monocytes in the tumor microenvironment to supporting tumor progression. Full article

(This article belongs to the Special Issue The Role of Chemerin in Human Disease)

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16 pages, 4128 KiB

Open AccessArticle

Divergence of Chemerin Reduction by an ATS9R Nanoparticle Targeting Adipose Tissue In Vitro vs. In Vivo in the Rat

by Alexis Orr, Kunli Liu, Adam E. Mullick, Xuefei Huang and Stephanie W. Watts

Biomedicines 2022, 10(7), 1635; https://doi.org/10.3390/biomedicines10071635 - 7 Jul 2022

Cited by 1 | Viewed by 2320

Abstract

Nanoparticles (NPs) can enable delivery of a drug to a targeted tissue. Previous studies have shown that an NP utilizing an adipose targeting sequence (ATS) peptide in conjunction with a drug can selectively deliver the drug to mouse adipose tissues, using the prohibitin protein expressed in adipose tissue as the target of the ATS. Adipose tissue is a major source of the adipokine chemerin, a prohypertensive protein. Liver-derived chemerin, the largest source of circulating chemerin, is biologically inactive in blood pressure regulation. Our goal is to understand if chemerin produced in adipose tissue contributes to blood pressure/hypertension. We hypothesize the ATS drug delivery system could be used specifically to reduce the levels of adipose tissue-derived chemerin. We created an NP consisting of an antisense oligonucleotide (ASO) against chemerin and a FITC-labeled ATS with a nine arginine sequence (ATS9R). In vitro studies showed that the ASO is functional when incorporated into an NP with ATS9R as it reduced chemerin mRNA expression in isolated epidydimal (Epi) and retroperitoneal (RP) fat adipocytes from Dahl SS rats. This same NP reduced chemerin in isolated whole fats. However, this NP was unable to selectively deliver the ASO to adipose tissue in vivo; liver delivery was dominant. Varying NP doses, administration route, and the concentration of components constituting the NP showed no improvement in ASO delivery to fats vs. the liver. Further studies are therefore needed to develop the ATS9R system to deliver an ASO to adipose beds in rats. Full article

(This article belongs to the Special Issue The Role of Chemerin in Human Disease)

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18 pages, 3221 KiB

Open AccessArticle

Chemerin Overexpression in the Liver Protects against Inflammation in Experimental Non-Alcoholic Steatohepatitis

by Rebekka Pohl, Susanne Feder, Elisabeth M. Haberl, Lisa Rein-Fischboeck, Thomas S. Weiss, Marlen Spirk, Astrid Bruckmann, Nichole McMullen, Christopher J. Sinal and Christa Buechler

Biomedicines 2022, 10(1), 132; https://doi.org/10.3390/biomedicines10010132 - 7 Jan 2022

Cited by 7 | Viewed by 2252

Abstract

Non-alcoholic steatohepatitis (NASH) is marked by macrophage infiltration and inflammation. Chemerin is a chemoattractant protein and is abundant in hepatocytes. The aim of this study was to gain insight into the role of hepatocyte-produced prochemerin in NASH. Therefore, mice were infected with adeno-associated virus 8 to direct hepatic overexpression of prochemerin in a methionine–choline deficient dietary model of NASH. At the end of the study, hepatic and serum chemerin were higher in the chemerin-expressing mice. These animals had less hepatic oxidative stress, F4/80 and CC-chemokine ligand 2 (CCL2) protein, and mRNA levels of inflammatory genes than the respective control animals. In order to identify the underlying mechanisms, prochemerin was expressed in hepatocytes and the hepatic stellate cells, LX-2. Here, chemerin had no effect on cell viability, production of inflammatory, or pro-fibrotic factors. Notably, cultivation of human peripheral blood mononuclear cells (PBMCs) in the supernatant of Huh7 cells overexpressing chemerin reduced CCL2, interleukin-6, and osteopontin levels in cell media. CCL2 was also low in RAW264.7 cells exposed to Hepa1–6 cell produced chemerin. In summary, the current study showed that prochemerin overexpression had little effect on hepatocytes and hepatic stellate cells. Of note, hepatocyte-produced chemerin deactivated PBMCs and protected against inflammation in experimental NASH. Full article

(This article belongs to the Special Issue The Role of Chemerin in Human Disease)

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Review

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23 pages, 2985 KiB

Open AccessReview

Chemerin Forms: Their Generation and Activity

by Lei Zhao, Lawrence L. Leung and John Morser

Biomedicines 2022, 10(8), 2018; https://doi.org/10.3390/biomedicines10082018 - 19 Aug 2022

Cited by 20 | Viewed by 3103

Abstract

Chemerin is the product of the RARRES2 gene which is secreted as a precursor of 143 amino acids. That precursor is inactive, but proteases from the coagulation and fibrinolytic cascades, as well as from inflammatory reactions, process the C-terminus of chemerin to first activate it and then subsequently inactivate it. Chemerin can signal via two G protein-coupled receptors, chem1 and chem2, as well as be bound to a third non-signaling receptor, CCRL2. Chemerin is produced by the liver and secreted into the circulation as a precursor, but it is also expressed in some tissues where it can be activated locally. This review discusses the specific tissue expression of the components of the chemerin system, and the role of different proteases in regulating the activation and inactivation of chemerin. Methods of identifying and determining the levels of different chemerin forms in both mass and activity assays are reviewed. The levels of chemerin in circulation are correlated with certain disease conditions, such as patients with obesity or diabetes, leading to the possibility of using chemerin as a biomarker. Full article

(This article belongs to the Special Issue The Role of Chemerin in Human Disease)

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21 pages, 1919 KiB

Open AccessReview

Chemerin: A Functional Adipokine in Reproductive Health and Diseases

by Ming Yu, Yali Yang, Chen Huang, Lei Ge, Li Xue, Zhonglin Xiao, Tianxia Xiao, Huashan Zhao, Peigen Ren and Jian V. Zhang

Biomedicines 2022, 10(8), 1910; https://doi.org/10.3390/biomedicines10081910 - 7 Aug 2022

Cited by 16 | Viewed by 4772

Abstract

As a multifaceted adipokine, chemerin has been found to perform functions vital for immunity, adiposity, and metabolism through its three known receptors (chemokine-like receptor 1, CMKLR1; G-protein-coupled receptor 1, GPR1; C-C motif chemokine receptor-like 2, CCRL2). Chemerin and the cognate receptors are also expressed in the hypothalamus, pituitary gland, testis, ovary, and placenta. Accumulating studies suggest that chemerin participates in normal reproduction and underlies the pathological mechanisms of certain reproductive system diseases, including polycystic ovary syndrome (PCOS), preeclampsia, and breast cancer. Herein, we present a comprehensive review of the roles of the chemerin system in multiple reproductive processes and human reproductive diseases, with a brief discussion and perspectives on future clinical applications. Full article

(This article belongs to the Special Issue The Role of Chemerin in Human Disease)

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13 pages, 1051 KiB

Open AccessReview

Chemerin as Potential Biomarker in Pediatric Diseases: A PRISMA-Compliant Study

by Katarzyna Zdanowicz, Anna Bobrus-Chociej and Dariusz Marek Lebensztejn

Biomedicines 2022, 10(3), 591; https://doi.org/10.3390/biomedicines10030591 - 3 Mar 2022

Cited by 10 | Viewed by 2957

Abstract

Adipose tissue is the main source of adipokines and therefore serves not only as a storage organ, but also has an endocrine effect. Chemerin, produced mainly in adipocytes and liver, is a natural ligand for chemokine-like receptor 1 (CMKLR1), G-protein-coupled receptor 1 (GPR1) and C-C motif chemokine receptor-like 2 (CCRL2), which have been identified in many tissues and organs. The role of this protein is an active area of research, and recent analyses suggest that chemerin contributes to angiogenesis, adipogenesis, glucose homeostasis and energy metabolism. Many studies confirm that this molecule is associated with obesity in both children and adults. We conducted a systematic review of data from published studies evaluating chemerin in children with various disease entities. We searched PubMed to identify eligible studies published prior to February 2022. A total of 36 studies were selected for analysis after a detailed investigation, which was intended to leave only the research studies. Moreover, chemerin seems to play an important role in the development of cardiovascular and digestive diseases. The purpose of this review was to describe the latest advances in knowledge of the role of chemerin in the pathogenesis of various diseases from studies in pediatric patients. The mechanisms underlying the function of chemerin in various diseases in children are still being investigated, and growing evidence suggests that this adipokine may be a potential prognostic biomarker for a wide range of diseases. Full article

(This article belongs to the Special Issue The Role of Chemerin in Human Disease)

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