Chemerin

Chemerin, also known as retinoic acid receptor responder protein 2 (RARRES2), tazarotene-induced gene 2 protein (TIG2), or RAR-responsive protein TIG2 is a is_associated_with::protein that in humans is encoded by the RARRES2 is_associated_with::gene.

Function
is_associated_with::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 is_associated_with::nuclear receptor proteins that are members of the steroid and thyroid hormone receptor superfamily of transcriptional regulators. is_associated_with::RARRES1, RARRES2 (this gene), and is_associated_with::RARRES3 are genes whose expression is upregulated by the synthetic retinoid is_associated_with::tazarotene. RARRES2 is thought to act as a cell surface receptor.

Chemerin is a is_associated_with::chemoattractant is_associated_with::protein that acts as a is_associated_with::ligand for the is_associated_with::G protein-coupled receptor is_associated_with::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 is_associated_with::C-terminus by inflammatory and coagulation is_associated_with::serine proteases.

Chemerin was found to stimulate is_associated_with::chemotaxis of is_associated_with::dendritic cells and is_associated_with::macrophages to the site of inflammation.

In humans, chemerin is_associated_with::mRNA is highly expressed in white is_associated_with::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 is_associated_with::adipocyte differentiation and glucose uptake, chemerin is classified as an is_associated_with::adipokine.

Role as an adipokine
Chemerin has been implicated in is_associated_with::autocrine / is_associated_with::paracrine signaling for adipocyte differentiation and also stimulation of is_associated_with::lipolysis. Studies with is_associated_with::3T3-L1 cells have shown chemerin expression is low in pre-differentiated is_associated_with::adipocytes but its expression and secretion increases both during and after differentiation is_associated_with::in vitro. Genetic knockdown of chemerin or its receptor, CMKLR1 impairs differentiation into adipocytes, and reduces the expression of is_associated_with::GLUT4 and is_associated_with::adiponectin, while increasing expression of IL-6 and is_associated_with::insulin receptor. Furthermore, post-differentiation knockdown of chemerin reduced GLUT4, is_associated_with::leptin, is_associated_with::adiponectin, is_associated_with::perilipin, and reduced is_associated_with::lipolysis, suggesting chemerin plays a role in metabolic function of mature adipocytes. Studies using mature human adipocytes, 3T3-L1 cells, and is_associated_with::in vivo studies in mice showed chemerin stimulates the is_associated_with::phosphorylation of the MAPKs, 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 is_associated_with::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 is_associated_with::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 is_associated_with::glucose tolerance and individuals with is_associated_with::type II diabetes and first degree relatives. Moreover, chemerin levels show a significant correlation with is_associated_with::body mass index, plasma is_associated_with::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.