Chemerin: A Functional Adipokine in Reproductive Health and Diseases

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.

The Role of Selected Adipocytokines in Ovarian Cancer and Endometrial Cancer

“…Prochemerin, on the other hand, undergoes further enzymatic processing and, as a result of the cleavage process at the carboxyl end by serine, cysteine and carboxypeptidase proteases, chemotactically active isoforms are formed, with chemerin 157 being the most active isoform. The enzymatic cleavage reaction can occur directly or sequentially [ 198 , 216 , 219 , 224 , 230 , 231 , 232 , 233 , 234 , 235 , 236 , 237 , 238 ].…”

“…The biological activity of chemokine isoforms is enabled by the existence of specific receptors, which include chemokine receptor 1 (also called chemokine-like receptor 1—CMKLR1), chemokine receptor 2—GPR1 (G Protein-Coupled Receptor 1), coupled to G protein, and chemokine-like receptor 2—CCRL2 (C-C Motif Chemokine Receptor Like 2) [ 227 , 236 , 238 , 239 ]. The CMKLR1 receptor is expressed mainly on the surface of monocytes, macrophages, Natural Killer cells (NK) and plasmocytoid dendritic cells, and its strong expression is found in adipose tissue.…”

Understanding the Role of Chemerin in the Pathophysiology of Pre-Eclampsia

“…GPR1 serves additionally as a scavenger receptor for peptides that cannot stimulate receptor activation. Interestingly, GPR1 is not expressed in monocytes, macrophages, or peripheral blood lymphocytes, but instead, it is expressed in cells related to the central nervous system [ 24 , 25 ]. Although chemerin is the only identified ligand for CCRL2, its interaction does not initiate any known signaling pathway; thus, its role remains uncertain; however, it seems to have the ability to amplify local chemerin concentration for CMKLR1 interaction [ 19 , 26 ].…”

“…The main biological functions of chemerin are its actions as an adipokine, chemoattractant, and growth factor [ 25 ]. As an adipokine, chemerin regulates glucose and lipid metabolism, affecting, e.g., lipid deposition in the endothelium, resulting in the progression of atherosclerosis and the development of insulin resistance and obesity [ 17 , 27 ].…”

“…In light of the wide range of biological chemerin functions presented here, recent research has revealed that this molecule is involved in the pathophysiology of many human diseases, such as obesity, diabetes, metabolic syndrome, cardiovascular diseases, cancer, liver failure, chronic pancreatitis, chronic kidney disease, and psoriasis [ 5 , 6 , 17 , 25 , 26 ]. In this review, we try to explain how different biological chemerin activities might be involved in PE pathophysiology.…”