Chemerin, also known asretinoic acid receptor responder protein 2 (RARRES2),tazarotene-induced gene 2 protein (TIG2), orRAR-responsive protein TIG2 is aprotein that in humans is encoded by theRARRES2gene.[5][6][7]
Retinoids 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 specificnuclear receptor proteins that are members of the steroid and thyroid hormone receptor superfamily of transcriptional regulators.RARRES1, RARRES2 (this gene), andRARRES3 are genes whose expression is upregulated by the synthetic retinoidtazarotene. RARRES2 is thought to act as a cell surface receptor.[7]
In humans, chemerinmRNA is highly expressed in whiteadipose tissue, liver and lung while its receptor, CMKLR1 is predominantly expressed in immune cells as well as adipose tissue.[11] Because of its role inadipocytedifferentiation and glucose uptake, chemerin is classified as anadipokine.
Chemerin has been implicated inautocrine /paracrine signaling for adipocyte differentiation and also stimulation oflipolysis.[11][12] Studies with3T3-L1 cells have shown chemerin expression is low in pre-differentiatedadipocytes[11] but its expression and secretion increases both during and after differentiationin vitro.Genetic knockdown of chemerin or its receptor, CMKLR1 impairs differentiation into adipocytes, and reduces the expression ofGLUT4 andadiponectin, while increasing expression ofIL-6 andinsulin receptor. Furthermore, post-differentiation knockdown of chemerin reduced GLUT4,leptin,adiponectin,perilipin, and reducedlipolysis, suggesting chemerin plays a role in metabolic function of mature adipocytes.[12] Studies using mature human adipocytes, 3T3-L1 cells, andin vivo studies in mice showed chemerin stimulates thephosphorylation of theMAPKs,ERK1, andERK2, which are involved in mediating lipolysis.[12]
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 thanthermogenesis.2
Given chemerin's role as a chemoattractant and a recent finding macrophages have been implicated in chronic inflammation of adipose tissue in obesity.[13] This suggests chemerin may play an important role in the pathogenesis of obesity andinsulin resistance.
Studies in mice found that feeding mice a high-fat diet resulted in increased expression of both chemerin and CMKLR1.[6] In humans, chemerin levels are significantly different between individuals with normalglucose tolerance and individuals withtype II diabetes and first degree relatives.[14] Moreover, chemerin levels show a significant correlation withbody mass index, plasmatriglyceride levels and blood pressure.[8]
It was found incubation of 3T3-L1 cells with recombinant human chemerin protein facilitated insulin-stimulated glucose uptake.[15] This suggests chemerin plays a role in insulin sensitivity and may be a potential therapeutic target for treating type II diabetes.[8]
^Schultz S, Saalbach A, Heiker JT, Meier R, Zellmann T, Simon JC, Beck-Sickinger AG (2013). "Proteolytic activation of prochemerin by kallikrein 7 breaks an ionic linkage and results in C-terminal rearrangement".Biochem. J.452 (2):271–80.doi:10.1042/BJ20121880.PMID23495698.
Yokoyama-Kobayashi M, Yamaguchi T, Sekine S, Kato S (1999). "Selection of cDNAs encoding putative type II membrane proteins on the cell surface from a human full-length cDNA bank".Gene.228 (1–2):161–7.doi:10.1016/S0378-1119(99)00004-9.PMID10072769.
