Chemerin

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Chemerin (also known as tazarotene-induced gene 2 TIG2, retinoic acid receptor responder 2 RARRES2) is a chemoattractant protein that acts as a ligand for the G-protein coupled receptor CMKLR1 (also known as ChemR23). Chemerin is a 14kDa[clarify] protein secreted in an inactive form as prochemerin and is activated through C-terminal cleavage[clarify] by inflammatory and coagulation serine proteases.[1]. Chemerin was found to stimulate chemotaxis of dendritic cells and macrophages to the site of inflammation.[2] In humans, chemerin mRNA is highly expressed[clarify] in white adipose tissue, liver and lung while its receptor, CMKLR1 is predominantly expressed in immune cells as well as adipose tissue.[3] Because of its role in adipocyte differentiation and insulin uptake, chemerin is classified as an adipokine.

[edit] Role as an adipokine

Chemerin has been implicated in autocrine/paracrine signaling for adipocyte differentiation and also stimulation of lipolysis.[4][5][6]

Studies with 3T3-L1 cells have shown chemerin expression is low in pre-differentiated[clarify] adipocyte s but its expression and secretion increases both during and after differentiatioin vitro. Genetic knockdown[clarify] 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.[7]

Studies using mature human adipocytes, 3T3-L1 cells, and in vivo studies in mice showed chemerin stimulates the phosphorylation of the MAPKs,[clarify] ERK1 and ERK2, which are involved in mediating lipolysis.[8][9]

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

[edit] 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,[10] this suggests chemerin may play an important 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.[11] 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,[clarify] and blood pressure.1

Interestingly, it was found incubation of 3T3-L1 cells with recombinant human chemerin protein facilitated insulin-stimulated glucose uptake.[12] This suggests chemerin plays a role in insulin sensitivity and may be a potential therapeutic target for treating type II diabetes.

[edit] Notes

  1. ^ Zabel et al. (2005) "Chemerin Activation by Serine Proteases of the Coagulation Fibrinolytic, and Inflammatory Cascades". J Biol Chem.[clarify] 280(41):34661-6
  2. ^ Wittamer et al. (2003) Specific Recruitment of Antigen-presenting Cells by Chemerin, a Novel Processed Ligand from Human Inflammatory Fluids. J Exp Med.[clarify] 198(7): 977-85.
  3. ^ Bozaoglu et al. "Chemerin Is a Novel Adipokine Associated with Obesity and Metabolic Syndrome". Endocrinology. 148(10): 4687-94
  4. ^ Bozaoglu et al. Chemerin Is a Novel Adipokine Associated with Obesity and Metabolic Syndrome. Endocrinology. 148(10): 4687-94.
  5. ^ Gorlaski et al. (2007) Chemerin, a Novel Adipokine That Regulates Adipogenesis and Adipocyte Metabolism. J Biol Chem.[clarify] 282(38): 28175-88.
  6. ^ Roh et al. (2007) Chemerin: A new adipokine that modulates adipogenesis via its own receptor. Biochem Biophys Res Commun.[clarify] 362(4):1013-8.
  7. ^ Gorlaski et al. (2007) Chemerin, a Novel Adipokine That Regulates Adipogenesis and Adipocyte Metabolism. J Biol Chem.[clarify] 282(38): 28175-88.
  8. ^ Gorlaski et al., 282(38): 28175-88.
  9. ^ Roh et al., 362(4):1013-8.
  10. ^ Xu, H. et al. (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest.[clarify] 112: 1821–1830.
  11. ^ Roh et al. (2007) Chemerin: A new adipokine that modulates adipogenesis via its own receptor. Biochem Biophys Res Commun. 362(4):1013-8
  12. ^ Takahashi et al. (2008) Chemerin enhances insulin signaling and potentiates insulin-stimulated glucose uptake in 3T3-L1 adipocytes. FEBS Lett.[clarify] 582(5): 573-8.