Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemerin acting via its distinct G protein-coupled receptor CMKLR1 (ChemR23), is a novel adipokine, circulating levels of which are raised in inflammatory states. Chemerin shows strong correlation with various facets of the metabolic syndrome; these states are associated with an increased incidence of cardiovascular disease (CVD) and dysregulated angiogenesis. We therefore, investigated the regulation of ChemR23 by pro-inflammatory cytokines and assessed the angiogenic potential of chemerin in human endothelial cells (EC). We have demonstrated the novel presence of ChemR23 in human ECs and its significant up-regulation (P<0.001) by pro-inflammatory cytokines, TNF-alpha, IL-1beta and IL-6. More importantly, chemerin was potently angiogenic, as assessed by conducting functional in-vitro angiogenic assays; chemerin also dose-dependently induced gelatinolytic (MMP-2 & MMP-9) activity of ECs (P<0.001). Furthermore, chemerin dose-dependently activated PI3K/Akt and MAPKs pathways (P<0.01), key angiogenic and cell survival cascades. Our data provide the first evidence of chemerin-induced endothelial angiogenesis and MMP production and activity.
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PMID:Identification of chemerin receptor (ChemR23) in human endothelial cells: chemerin-induced endothelial angiogenesis. 2004 79

Chemerin is an adipokine with important regulatory roles in adipogenesis. In humans, serum total chemerin (i.e. prochemerin plus chemerin) levels are positively associated with body mass index and metabolic syndrome. However, the mechanisms that increase serum chemerin concentration are unknown. We hypothesized that chronic low-grade inflammation that occurs in obesity promotes chemerin production by adipocytes. Consistent with this, TNFalpha treatment of 3T3-L1 adipocytes increased bioactive chemerin levels in the cell media as detected using a CMKLR1 cell-based bioassay. This effect was blocked by the protein synthesis inhibitor cycloheximide and protein secretion inhibitor brefeldin A, indicating that TNFalpha may enhance prochemerin synthesis and secretion from adipocytes. In vivo, TNFalpha produced a time-dependent increase in serum total chemerin and bioactive chemerin. Bioactive chemerin was produced by primary mouse adipocytes and hepatocytes. Only primary adipocyte-derived chemerin was responsive to TNFalpha regulation implicating adipocytes as a potential source of elevated serum chemerin after TNFalpha exposure in vivo. In lean mice, serum total chemerin levels oscillated with peak levels occurring during daytime and trough levels at night. Comparatively, leptin- and leptin receptor-deficient obese mice, which have elevated adipose tissue expression of TNFalpha, displayed elevated serum total chemerin levels with an enhanced oscillatory pattern. In summary, our novel results identified TNFalpha as a positive regulator of adipocyte-derived chemerin. We corroborate the finding of elevated chemerin in obese humans by identifying elevated serum levels of total chemerin in two obese mouse models with a corresponding alteration in the rhythmic pattern of serum chemerin levels.
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PMID:Serum chemerin levels vary with time of day and are modified by obesity and tumor necrosis factor-{alpha}. 2036 80

Vascular remodeling is a characteristic pathogenesis of hypertension and a main cause of abnormal construction and function of organs because of hypertension. Chemerin is a new adipokine that is elevated in states of obesity and metabolic syndrome (MS). However, the molecular mechanisms behind these pathological processes are not fully clarified. An animal model of metabolic hypertension was created to evaluate the role of metabolic chemerin in hypertension. In this study, the expression of chemerin/CMKLR-1 and autophagy in the arteries of metabolic hypertension rats undergoing vascular remodeling was investigated and the effect and mechanisms on the regulation of human aortic smooth muscle cells (HA-SMCs) were explored. The vascular remodeling in vivo was more serious in the metabolic hypertensive rat model, and the expression of chemerin and its receptor CMKLR1 were remarkably higher in the media layer of the thoracic aorta and the mesenteric artery in metabolic hypertension rats. In addition, there was an increased number of autophagosomes in SMCs and an up-regulation of the autophagy-related protein LC3 and beclin-1 levels in metabolic hypertension rats. In vitro, chemerin significantly stimulated HA-SMC proliferation and migration, as determined by MTT assay and scratch assay, respectively. Chemerin significantly increased LC3 and beclin-1 levels, as measured by western blot analysis, while this effect was inhibited by the autophagy inhibitor 3-MA. It is demonstrated that chemerin stimulates SMC proliferation and migration via autophagy, which may lead to vascular structural remodeling in metabolic hypertension.
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PMID:Chemerin stimulates aortic smooth muscle cell proliferation and migration via activation of autophagy in VSMCs of metabolic hypertension rats. 3097 65