Chemerin Is a Novel Adipokine Associated with Obesity and Metabolic Syndrome

Metabolic Research Unit, School of Exercise and Nutrition Sciences, Deakin University, Pigdons Road, Waurn Ponds, Geelong, Victoria 3217, Australia.
Endocrinology (Impact Factor: 4.64). 11/2007; 148(10):4687-94. DOI: 10.1210/en.2007-0175
Source: PubMed

ABSTRACT Soluble protein hormones are key regulators of a number of metabolic processes, including food intake and insulin sensitivity. We have used a signal sequence trap to identify genes that encode secreted or membrane-bound proteins in Psammomys obesus, an animal model of obesity and type 2 diabetes (T2D). Using this signal sequence trap, we identified the chemokine chemerin as being a novel adipokine. Gene expression of chemerin and its receptor, chemokine-like receptor 1 (CMKLR1), was significantly higher in adipose tissue of obese and type 2 diabetic P. obesus compared with lean, normoglycemic P. obesus. Fractionation of P. obesus adipose tissue confirmed that chemerin was predominantly expressed in adipocytes, whereas CMKLR1 was expressed in both adipocytes and stromal-vascular cells of adipose tissue. In 3T3-L1 adipocytes, chemerin was markedly induced during differentiation, whereas CMKLR1 was down-regulated during differentiation. Serum chemerin levels were measured by ELISA in human plasma samples from 114 subjects with T2D and 142 normal glucose tolerant controls. Plasma chemerin levels were not significantly different between subjects with T2D and normal controls. However, in normal glucose tolerant subjects, plasma chemerin levels were significantly associated with body mass index, circulating triglycerides, and blood pressure. Here we report, for the first time, that chemerin is an adipokine, and circulating levels of chemerin are associated with several key aspects of metabolic syndrome.

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Available from: Greg R Collier, Jul 06, 2015
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    ABSTRACT: The discovery of several adipokines with diverse activities and their involvement in regulation of various pathophysiological functions of human body has challenged the researchers. In the family of adipokine, chemerin is a novel and unique addition. Ever since the first report on chemerin as a chemo- attractant protein, there are numerous studies showing a multitasking capacity of chemerin in the maintenance of homeostasis, for the activation of natural killer cells, macrophages and dendritic cells in both innate and adaptive immunity. Its diversity ranges from generalized inflammatory cascades to being explicitly involved in the manifestation of arthritis psoriasis, and peritonitis. Its association with certain cancerous tissue may render it as a potential tumor marker. In present review, we aim to consolidate recent data of investigations on chemerin in context to functional characteristics with a special reference to its role as a metabolic signal in inflammation and non-metabolic syndromes.
    Peptides 09/2014; DOI:10.1016/j.peptides.2014.09.019 · 2.61 Impact Factor
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    ABSTRACT: Introduction. Chemerin seems to be involved in pathogenesis of chronic hepatitis C (CHC). Hepatic expressions of chemerin and its receptor, chemokine receptor-like 1 (CMKLR1), in CHC have not been studied so far. Aim. To evaluate chemerin and CMKLR1 hepatic expression together with serum chemerin concentration in CHC patients and to assess their relationship with metabolic and histopathological abnormalities. Methods. The study included 63 nonobese CHC patients. Transcription of chemerin and CMKLR1 was assessed by quantitative real-time PCR, while serum chemerin was assessed by enzyme-linked immunosorbent assay. Results. Expression of chemerin and CMKLR1 was present in the liver of all CHC patients regardless of sex or age. This expression was not associated with necroinflammatory activity and steatosis grade, fibrosis stage, and metabolic abnormalities. There was a negative association between serum chemerin and chemerin hepatic expression (r = (-0.41), P = 0.006). Conclusion. The study for the first time confirmed a marked expression of chemerin and CMKLR1 in the liver of CHC patients. The study was performed using the homogenates of human liver tissue, so it is not possible to define whether hepatocytes or other cell types which are abundantly represented in the liver constitute the main source of chemerin and CMKLR1 mRNA.
    BioMed Research International 07/2014; 2014:517820. DOI:10.1155/2014/517820 · 2.71 Impact Factor
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    ABSTRACT: CHEMERIN or RARRES2 is a new adipokine that is involved in the regulation of adipogenesis, energy metabolism and inflammation. Recent data suggest that it also plays a role in reproductive function in rats and humans. Here we studied the expression of CHEMERIN and its three receptors (CMKLR1, GPR1 and CCRL2) in the bovine ovary and investigated the in vitro effects of this hormone on granulosa cell steroidogenesis and oocyte maturation. By RT-PCR, immunoblotting and immunohistochemistry, we found CHEMERIN, CMKLR1, GPR1 and CCRL2 in various ovarian cells, including granulosa and theca cells, corpus luteum, and oocytes. In cultured bovine granulosa cells, INSULIN, IGF1 and two insulin sensitizers, metformin and rosiglitazone increased rarres2 mRNA expression whereas they decreased cmklr1, gpr1 and cclr2 mRNA expression. Furthermore, TNF alpha and ADIPONECTIN significantly increased rarres2 and cmklr1 expression, respectively. In cultured bovine granulosa cells, human recombinant CHEMERIN (hRec, 200 ng/ml) reduced production of both progesterone and estradiol, cholesterol content, STAR abundance, CYP19A1 and HMGCR proteins, and the phosphorylation levels of MAPK3/MAPK1 in the presence or absence of FSH (10(-8) M) and IGF1 (10(-8) M). All these effects were abolished by using an anti-CMKLR1 antibody. In bovine cumulus-oocyte complexes, the addition of hRec (200 ng/ml) in the maturation medium arrested most oocytes at the GV stage and this was associated with a decrease in MAPK3/1 phosphorylation in both oocytes and cumulus cells. Thus, in cultured bovine granulosa cells, hRec decreases steroidogenesis, cholesterol synthesis and MAPK3/1 phosphorylation probably through CMKLR1. Moreover, in cumulus-oocyte complexes, it blocked meiotic progression at the germinal vesicle stage and inhibited MAPK3/1 phosphorylation in both the oocytes and cumulus cells during in vitro maturation.
    Biology of Reproduction 03/2014; 90(5). DOI:10.1095/biolreprod.113.117044 · 3.45 Impact Factor