Chemerin
Encyclopedia
Chemerin, also known as retinoic acid receptor responder protein 2 (RARRES2), tazarotene-induced gene 2 protein (TIG2), or RAR-responsive protein TIG2 is a protein
that in humans is encoded by the RARRES2 gene
.
s exert biologic effects such as potent growth inhibitory and cell differentiation activities and are used in the treatment of hyperproliferative dermatological diseases. These effects are mediated by specific nuclear receptor
proteins that are members of the steroid and thyroid hormone receptor superfamily of transcriptional regulators. RARRES1
, RARRES2 (this gene), and RARRES3
are genes whose expression is upregulated by the synthetic retinoid tazarotene
. RARRES2 is thought to act as a cell surface receptor.
Chemerin is a chemoattractant protein
that acts as a ligand
for the G protein-coupled receptor
CMKLR1
(also known as ChemR23). Chemerin is a 14 kDa protein secreted in an inactive form as prochemerin and is activated through cleavage of the C-terminus by inflammatory and coagulation serine protease
s.
Chemerin was found to stimulate chemotaxis
of dendritic cells and macrophage
s to the site of inflammation.
In humans, chemerin mRNA is highly expressed in white adipose tissue, liver and lung while its receptor, CMKLR1 is predominantly expressed in immune cells as well as adipose tissue. Because of its role in adipocyte
differentiation and glucose uptake, chemerin is classified as an adipokine
.
. Studies with 3T3-L1
cells have shown chemerin expression is low in pre-differentiated adipocyte
s but its expression and secretion increases both during and after differentiation in vitro
. Genetic knockdown
of chemerin or its receptor, CMKLR1 impairs differentiation into adipocytes, and reduces the expression of GLUT4
and adiponectin
, while increasing expression of IL-6
and insulin receptor
. Furthermore, post-differentiation knockdown of chemerin reduced GLUT4, leptin
, adiponectin
, perilipin
, and reduced lipolysis
, suggesting chemerin plays a role in metabolic function of mature adipocytes. Studies using mature human adipocytes, 3T3-L1 cells, and in vivo
studies in mice showed chemerin stimulates the phosphorylation
of the MAPK
s, ERK1
, and ERK2
, which are involved in mediating lipolysis.
Studies in mice have shown neither chemerin nor CMKLR1 are highly expressed in brown adipose tissue, indicating that chemerin plays a role in energy storage rather than thermogenesis
.2
.
Studies in mice found that feeding mice a high-fat diet, resulted in increased expression of both chemerin and CMKLR1. In humans, chemerin levels are not significantly different between individuals with normal glucose tolerance and individuals with type II diabetes. However, chemerin levels show a significant correlation with body mass index
, plasma triglyceride
levels and blood pressure.
Interestingly, it was found incubation of 3T3-L1 cells with recombinant human chemerin protein facilitated insulin-stimulated glucose uptake. This suggests chemerin plays a role in insulin sensitivity and may be a potential therapeutic target for treating type II diabetes.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the RARRES2 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
RetinoidRetinoid
The retinoids are a class of chemical compounds that are related chemically to vitamin A. Retinoids are used in medicine, primarily due to the way they regulate epithelial cell growth....
s exert biologic effects such as potent growth inhibitory and cell differentiation activities and are used in the treatment of hyperproliferative dermatological diseases. These effects are mediated by specific nuclear receptor
Nuclear receptor
In the field of molecular biology, nuclear receptors are a class of proteins found within cells that are responsible for sensing steroid and thyroid hormones and certain other molecules...
proteins that are members of the steroid and thyroid hormone receptor superfamily of transcriptional regulators. RARRES1
RARRES1
Retinoic acid receptor responder protein 1 is a protein that in humans is encoded by the RARRES1 gene.-Further reading:...
, RARRES2 (this gene), and RARRES3
RARRES3
Retinoic acid receptor responder protein 3 is a protein that in humans is encoded by the RARRES3 gene.-Further reading:...
are genes whose expression is upregulated by the synthetic retinoid tazarotene
Tazarotene
Tazarotene is a prescription topical retinoid sold as a cream or gel. This medication is approved for treatment of psoriasis, acne, and sun damaged skin...
. RARRES2 is thought to act as a cell surface receptor.
Chemerin is a chemoattractant protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that acts as a ligand
Ligand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...
for the G protein-coupled receptor
G protein-coupled receptor
G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...
CMKLR1
CMKLR1
Chemokine receptor-like 1 also known as ChemR23 is a protein that in humans is encoded by the CMKLR1 gene. Chemokine receptor-like 1 is a G protein-coupled receptor for the chemoattractant adipokine chemerin and the omega-3 fatty acid derived molecule resolvin E1...
(also known as ChemR23). Chemerin is a 14 kDa protein secreted in an inactive form as prochemerin and is activated through cleavage of the C-terminus by inflammatory and coagulation serine protease
Serine protease
Serine proteases are enzymes that cleave peptide bonds in proteins, in which serine serves as the nucleophilic amino acid at the active site.They are found ubiquitously in both eukaryotes and prokaryotes...
s.
Chemerin was found to stimulate chemotaxis
Chemotaxis
Chemotaxis is the phenomenon in which somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. This is important for bacteria to find food by swimming towards the highest concentration of food molecules,...
of dendritic cells and macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
s to the site of inflammation.
In humans, chemerin mRNA is highly expressed in white adipose tissue, liver and lung while its receptor, CMKLR1 is predominantly expressed in immune cells as well as adipose tissue. Because of its role in adipocyte
Adipocyte
However, in some reports and textbooks, the number of fat cell increased in childhood and adolescence. The total number is constant in both obese and lean adult...
differentiation and glucose uptake, chemerin is classified as an adipokine
Adipokine
The adipokines or adipocytokines are cytokines secreted by adipose tissue.Members include:* chemerin* interleukin-6...
.
Role as an adipokine
Chemerin has been implicated in autocrine / paracrine signaling for adipocyte differentiation and also stimulation of lipolysisLipolysis
Lipolysis is the breakdown of lipids and involves the hydrolysis of triglycerides into free fatty acids followed by further degradation into acetyl units by beta oxidation. The process produces Ketones, which are found in large quantities in ketosis, a metabolic state that occurs when the liver...
. Studies with 3T3-L1
3T3-L1
3T3-L1 is a cell line derived from 3T3 cells that is used in biological research on adipose tissue. 3T3-L1 cells have a fibroblast-like morphology, but, under appropriate conditions, the cells differentiate into an adipocyte-like phenotype....
cells have shown chemerin expression is low in pre-differentiated adipocyte
Adipocyte
However, in some reports and textbooks, the number of fat cell increased in childhood and adolescence. The total number is constant in both obese and lean adult...
s but its expression and secretion increases both during and after differentiation in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
. Genetic knockdown
Gene knockdown
Gene knockdown refers to techniques by which the expression of one or more of an organism's genes is reduced, either through genetic modification or by treatment with a reagent such as a short DNA or RNA oligonucleotide with a sequence complementary to either an mRNA transcript or a gene...
of chemerin or its receptor, CMKLR1 impairs differentiation into adipocytes, and reduces the expression of GLUT4
GLUT4
Glucose transporter type 4, also known as GLUT4, is a protein that in humans is encoded by the GLUT4 gene. GLUT4 is the insulin-regulated glucose transporter found in adipose tissues and striated muscle that is responsible for insulin-regulated glucose translocation into the cell...
and adiponectin
Adiponectin
Adiponectin is a protein which in humans is encoded by the ADIPOQ gene.- Structure :...
, while increasing expression of IL-6
Interleukin 6
Interleukin-6 is a protein that in humans is encoded by the IL6 gene.IL-6 is an interleukin that acts as both a pro-inflammatory and anti-inflammatory cytokine. It is secreted by T cells and macrophages to stimulate immune response, e.g. during infection and after trauma, especially burns or other...
and insulin receptor
Insulin receptor
In molecular biology, the insulin receptor is a transmembrane receptor that is activated by insulin. It belongs to the large class of tyrosine kinase receptors....
. Furthermore, post-differentiation knockdown of chemerin reduced GLUT4, leptin
Leptin
Leptin is a 16 kDa protein hormone that plays a key role in regulating energy intake and energy expenditure, including appetite and metabolism. It is one of the most important adipose derived hormones...
, adiponectin
Adiponectin
Adiponectin is a protein which in humans is encoded by the ADIPOQ gene.- Structure :...
, perilipin
Perilipin
Perilipin, also known as lipid droplet-associated protein or PLIN, is a protein that, in humans, is encoded by the PLIN gene.- Function :Perilipin is a protein that coats lipid droplets in adipocytes, the fat-storing cells in adipose tissue...
, and reduced lipolysis
Lipolysis
Lipolysis is the breakdown of lipids and involves the hydrolysis of triglycerides into free fatty acids followed by further degradation into acetyl units by beta oxidation. The process produces Ketones, which are found in large quantities in ketosis, a metabolic state that occurs when the liver...
, suggesting chemerin plays a role in metabolic function of mature adipocytes. Studies using mature human adipocytes, 3T3-L1 cells, and in vivo
In vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
studies in mice showed chemerin stimulates the phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
of the MAPK
Mitogen-activated protein kinase
Mitogen-activated protein kinases are serine/threonine-specific protein kinases that respond to extracellular stimuli and regulate various cellular activities, such as gene expression, mitosis, differentiation, proliferation, and cell survival/apoptosis.-Activation:MAP kinases are activated...
s, ERK1
MAPK3
Mitogen-activated protein kinase 3 is an enzyme that in humans is encoded by the MAPK3 gene.-Interactions:MAPK3 has been shown to interact with PTPN7, SPIB, GTF2I, DUSP3, HDAC4, RPS6KA2, MAP2K1, DUSP6 and MAP2K2.-Further reading:...
, and ERK2
MAPK1
Mitogen-activated protein kinase 1, also known as MAPK1, p42MAPK, and ERK2, is an enzyme that in humans is encoded by the MAPK1 gene.- Function :The protein encoded by this gene is a member of the MAP kinase family...
, which are involved in mediating lipolysis.
Studies in mice have shown neither chemerin nor CMKLR1 are highly expressed in brown adipose tissue, indicating that chemerin plays a role in energy storage rather than thermogenesis
Thermogenesis
Thermogenesis is the process of heat production in organisms. It occurs mostly in warm-blooded animals, but a few species of thermogenic plants exist.-Types:...
.2
Role in obesity and diabetes
Given chemerin’s role as a chemoattractant and a recent finding macrophages have been implicated in chronic inflammation of adipose tissue in obesity. This suggests chemerin may play an important in the pathogenesis of obesity and insulin resistanceInsulin resistance
Insulin resistance is a physiological condition where the natural hormone insulin becomes less effective at lowering blood sugars. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions. Certain cell types...
.
Studies in mice found that feeding mice a high-fat diet, resulted in increased expression of both chemerin and CMKLR1. In humans, chemerin levels are not significantly different between individuals with normal glucose tolerance and individuals with type II diabetes. However, chemerin levels show a significant correlation with body mass index
Body mass index
The body mass index , or Quetelet index, is a heuristic proxy for human body fat based on an individual's weight and height. BMI does not actually measure the percentage of body fat. It was invented between 1830 and 1850 by the Belgian polymath Adolphe Quetelet during the course of developing...
, plasma triglyceride
Triglyceride
A triglyceride is an ester derived from glycerol and three fatty acids. There are many triglycerides, depending on the oil source, some are highly unsaturated, some less so....
levels and blood pressure.
Interestingly, it was found incubation of 3T3-L1 cells with recombinant human chemerin protein facilitated insulin-stimulated glucose uptake. This suggests chemerin plays a role in insulin sensitivity and may be a potential therapeutic target for treating type II diabetes.