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 RARRES2gene.
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 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.
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 adipocytedifferentiation and glucose uptake, chemerin is classified as an adipokine.
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
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 role in the pathogenesis of obesity and insulin resistance.
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 significantly different between individuals with normal glucose tolerance and individuals with type II diabetes and first degree relatives. Moreover, chemerin levels show a significant correlation with body mass index, plasma triglyceride levels and blood pressure.
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.
↑ 2.02.1Roh SG, Song SH, Choi KC, Katoh K, Wittamer V, Parmentier M, Sasaki S (Sep 2007). "Chemerin--a new adipokine that modulates adipogenesis via its own receptor". Biochem. Biophys. Res. Commun. 362 (4): 1013–8. doi:10.1016/j.bbrc.2007.08.104. PMID17767914.
↑ 4.04.14.2Zabel BA, Allen SJ, Kulig P, Allen JA, Cichy J, Handel TM, Butcher EC (October 2005). "Chemerin activation by serine proteases of the coagulation, fibrinolytic, and inflammatory cascades". J. Biol. Chem. 280 (41): 34661–6. doi:10.1074/jbc.M504868200. PMID16096270.
↑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.
↑Takahashi M, Takahashi Y, Takahashi K, Zolotaryov FN, Hong KS, Kitazawa R, Iida K, Okimura Y, Kaji H, Kitazawa S, Kasuga M, Chihara K (March 2008). "Chemerin enhances insulin signaling and potentiates insulin-stimulated glucose uptake in 3T3-L1 adipocytes". FEBS Lett. 582 (5): 573–8. doi:10.1016/j.febslet.2008.01.023. PMID18242188.
Nagpal S, Patel S, Jacobe H, DiSepio D, Ghosn C, Malhotra M, Teng M, Duvic M, Chandraratna RA (1997). "Tazarotene-induced gene 2 (TIG2), a novel retinoid-responsive gene in skin". J. Invest. Dermatol. 109 (1): 91–5. doi:10.1111/1523-1747.ep12276660. PMID9204961.
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.
Wittamer V, Bondue B, Guillabert A, Vassart G, Parmentier M, Communi D (2005). "Neutrophil-mediated maturation of chemerin: a link between innate and adaptive immunity". J. Immunol. 175 (1): 487–93. doi:10.4049/jimmunol.175.1.487. PMID15972683.