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: 4.5). 11/2007; 148(10):4687-94. DOI: 10.1210/en.2007-0175
Source: PubMed


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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    • "DHA appears to be the strongest anti-inflammatory compound among the tested ones as this fatty acid decreased expression of three out of four investigated proinflammatory cytokines. We also for the first time report effects of bioactive compounds on chemerin – an insulin resistance inducing cytokine[8], which is largely secreted by adipocytes. DHA was the only compound suppressing chemerin secretion, which was antagonized by AC. "
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    ABSTRACT: Background: Previous studies suggest that intake of specific bioactive compounds may have beneficial clinical effects on adipose tissue partly due to their anti-inflammatory and insulin-sensitizing properties. With the overall aim to contribute to better understanding of the mechanisms of selected bioactive nutrients on fat metabolism, we investigated their role on human white adipocyte function. Methods: The influence of the omega-3-fatty acid docosahexaenoic acid (DHA), the anthocyanin (AC) cyanidin-3-glucoside and its metabolite protocatechuic acid, and the beta-glucan metabolite propionic acid (PI) on adipokine secretion, fatty acid metabolism (lipolysis/lipogenesis) and adipocyte differentiation (lipid accumulation) was studied in human fat cells differentiated in vitro. To investigate possible synergistic, additive or antagonistic effects, DHA was also combined with AC or PI. Results: Each compound, alone or together with DHA, suppressed basal adipocyte lipolysis compared to control treated cells. DHA alone attenuated the secretion of pro-inflammatory adipokines such as chemerin, interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1/CCL2), whereas AC suppressed only the latter two. Treatment with PI decreased IL-6, tumour necrosis factor alpha (TNFα) and adiponectin secretion. A combination of DHA and AC decreased TNFα secretion and increased insulin-stimulated lipogenesis. No effect was found on adipocyte differentiation. At the selected concentrations, none of the compounds was found to be cytotoxic. Conclusion: The studied bioactive food compounds or their metabolites have beneficial effects in human primary fat cells measured as decreased basal lipolytic activity and secretion of inflammatory markers. A minor effect was also observed on insulin-stimulated glucose uptake albeit only with the combination of DHA and AC. Taken together, our results may link the reported health benefits of the selected bioactives on metabolic disorders such as insulin resistance, hypertension and dyslipidemia to effects on white adipocytes.
    Full-text · Article · Jan 2016 · Nutrition & Metabolism
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    • "In our study, both the total group and overweight group showed an liver attenuation, liver index and liver/spleen index decrease with a chemerin level increase. Non-alcoholic fatty liver disease cases are often characterized with elevated liver serum transaminases, but the international available studies usually do not find an ALT relation with the blood chemerin level[4,6,891024,31,32]. Only some studies have demonstrated such relevance[28]. "

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    • "An in vitro experiment showed that Chemerin and CMKLR1 were necessary for adipogenesis (Goralski et al., 2007; Roh et al., 2007). Knockdown of Chemerin in 3T3-L1 pre-adipocytes (Bozaoglu et al., 2007) and human multi-potent bone marrow-derived stromal cells (Muruganandan et al., 2010) abrogates adipogenesis, suggesting that Chemerin is necessary for adipocyte differentiation. Chemerin mainly impacts the mitotic clonal expansion phase in the first days of differentiation and has no effect on adipogenesis when knocked down in later phases of differentiation. "
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    ABSTRACT: Chemerin is an adipocyte-secreted adipokine that regulates the differentiation and metabolism of adipose through auto-/paracrine signaling. Its function in the differentiation of multipotent myoblast cells has thus far received little attention. In this study, C2C12 myoblast cells were cultured in the medium with Chemerin, and the differentiation potential of C2C12 myoblasts was analyzed. The results showed that Chemerin increased ROS levels and TG content of C2C12 cells. At the same time, the mRNA expressions and protein concentrations of the adipogenic factors PPARγ, C/EBPα and UCP1 were up-regulated, while the muscle specific transcription factors MyoD, Myogenin and MyHC were decreased in cultured C2C12 cells. In conclusion, the adipokine Chemerin promoted the adipogenic differentiation potential and altered the fate of myoblast cells from myogenesis to adipogenesis, which contributed in part to the up-regulated adipocyte genes. Our study reveals the importance of functional Chemerin signaling in adipogenesis and in directing the differentiation of multipotent myoblast cells. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Full-text · Article · Jul 2015 · Molecular and Cellular Endocrinology
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