SummaryBackground The adipokine chemerin modulates the function of innate immune cells and may link obesity and inflammation, and therefore, a possible relation of chemerin to inflammatory proteins in obesity and type 2 diabetes (T2D) was analysed. As visceral fat contributes to systemic inflammation, chemerin was measured in portal venous (PVS), hepatic venous (HVS) and systemic venous (SVS) blood of patients with liver cirrhosis. Patients and methods Systemic chemerin was determined by ELISA in the serum of normal-weight, overweight and T2D males, in the serum of T2D patients of both sexes, and in PVS, HVS and SVS of patients with liver cirrhosis. Results Circulating chemerin was similar in T2D and obese individuals but was significantly elevated in both cohorts compared to normal-weight individuals. Chemerin positively correlated with leptin, resistin and C-reactive protein (CRP). In T2D, chemerin was similar in male and female patients and increased in patients with elevated CRP. Chemerin was similar in PVS and SVS, indicating that visceral fat is not a major site of chemerin synthesis. Higher levels of chemerin in HVS demonstrate that chemerin is also released by the liver. Conclusions Visceral fat is not a major site of chemerin release, and elevated systemic levels of chemerin in obesity and T2D seem to be associated with inflammation rather than body mass index.
Systemic galectin-3 is elevated in obesity and negatively correlates with glycated hemoglobin in T2D patients, pointing to a modifying function of galectin-3 in human metabolic diseases.
Serum collection and IBD biobank supported by the Bundesministerium für Bildung und Forschung (German Ministry of Education and Research), Kompetenznetz chronisch entzündliche Darmerkrankungen (Competence network "Inflammatory Bowel Disease").
AbstractChemerin is an adipose tissue-secreted protein that stimulates chemotaxis of cells of the innate immune system. Inflammatory bowel disease (IBD) is linked to an impaired immune response and, therefore, we hypothesized that systemic chemerin may be altered in IBDpatients. Serum was collected from patients with Crohn´s disease (CD, 230 patients), ulcerative colitis (UC, 80 patients) and healthy controls (HC, 80 probands). Chemerin and adiponectin, which has already been measured in the serum of similar cohorts by others, were determined by ELISA. Sytemic chemerin concentrations were significantly elevated in serum of CD and UC patients compared to HC, and were also found to be higher in the serum of males with CD compared to males with UC. Adiponectin levels were lower in CD compared to UC and HC with similar circulating concentrations. In serum of male but not female patients chemerin levels were higher in UC patients with active disease whereas adiponectin was reduced. In CD elevated chemerin was associated with remission in males only.Treatment with corticosteroids was linked to elevated adiponectin in male CD patients and higher chemerin in female UC patients. Unlike adiponectin that is elevated in female serum in all cohorts analysed, chemerin was only higher in the serum of female UC patients.These data indicate that the levels of circulating chemerin are elevated in patients suffering from UC and CD whereas adiponectin is reduced in the latter. Relations of the systemic 2 concentrations of these adipokines to disease activity and treatment are disease-and genderspecific.3
Chemerin is an adipokine whose systemic concentration and adipose tissue expression is increased in obesity. Chemerin is highly abundant in adipocytes, yet the molecular mechanisms mediating its further induction in obesity have not been clarified. Adipocyte hypertrophy contributes to dysregulated adipokine synthesis, and we hypothesized that excess loading with free fatty acids (FFA) stimulates chemerin synthesis. Chemerin was expressed in mature adipocytes, and differentiation of 3T3-L1 cells in the presence of FFA further increased its level. TNF and IL-6 were induced by FFA, but concentrations were too low to up-regulate chemerin. Sterol regulatory element-binding protein 2 (SREBP2) was activated in these cells, indicative for cholesterol shortage. Suppression of cholesterol synthesis by lovastatin led to activation of SREBP2 and increased chemerin, and supplementation with mevalonate reversed this effect. Knockdown of SREBP2 reduced basal and FFA-induced chemerin. EMSA confirmed binding of 3T3-L1 adipocyte nuclear proteins to a SREBP site in the chemerin promotor. SREBP2 was activated and chemerin was induced in adipose tissue of mice fed a high-fat diet, and higher systemic levels seem to be derived from adipocytes. Lipopolysaccharide-mediated elevation of chemerin was similarly effective as induction by FFA, indicating that both mechanisms are equally important. Chemokine-like receptor 1 was not altered by the incubations mentioned above, and higher expression in fat of mice fed a high-fat diet may reflect increased number of adipose tissue-resident macrophages in obesity. In conclusion, the current data show that adipocyte hypertrophy and chronic inflammation are equally important in inducing chemerin synthesis.
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