Background As two novel adipocytokines, chemerin and apelin play a key role in the pathological process of insulin resistance （IR）, glucose metabolism and obesity, researchers have found that the levels of chemerin ...Background As two novel adipocytokines, chemerin and apelin play a key role in the pathological process of insulin resistance （IR）, glucose metabolism and obesity, researchers have found that the levels of chemerin and apelin changed significantly in type 2 diabetic patients with obesity, however, the underlying mechanism involved remains unclear. The aim of this study was to investigate whether chemerin and apelin play an important role in the pathophysiologic proceeding of diabetes. Methods This study enrolled 81 newly diagnosed obese type 2 diabetes mellitus （T2DM） patients （T2DM group, n=81）. All the patients were randomly assigned to DM1 group treated with metformin （n=41） and DM2 group treated with pioglitazone （n=40）. After hypoglycemic agents treatment, patients under better blood glucose control were chosen to be given antioxidant treatment. Another 79 subjects without T2DM were recruited as normal control group （NC group）, including 40 subjects （NC1 group） with normal body mass index （BMI） and 39 obese subjects （NC2 group）. Levels of chemerin, apelin, BMI, tumor necrosis factor-α（TNF-α）, homeostasis model assessment of IR （HOMA-IR） and 8-isoprotaglandim F2α（8-iso-PGF2α） were examined at baseline and post-treatment. The relationship between chemerin, apelin and BMI, TNF-α, HOMA-IR, 8-iso-PGF2α was analyzed. Results The baseline levels of chemerin, apelin, TNF-α, HOMA-IR and 8-iso-PGF2α in T2DM group were significantly higher than normal control group （P 〈0.001）. All indices mentioned above were significantly decreased after treatment （P 〈0.05）. In T2DM patients treated with pioglitazone, indices mentioned above except for HOMA-IR, were decreased significantly compared with patients treated with mefformin （P〈0.05）. After antioxidant treatment using lipoic acid, levels of chemerin, apelin, TNF-α and 8-iso-PGF2α were further significantly decreased （P 〈0.05）. Correlation analysis showed that the levels of chemerin and apelin c展开更多
Chemerin is present in various inflammatory sites and is closely involved in tissue inflammation. Recent studies have demonstrated that chemerin treatment can cause either anti-inflammatory or pro-inflammatory effects...Chemerin is present in various inflammatory sites and is closely involved in tissue inflammation. Recent studies have demonstrated that chemerin treatment can cause either anti-inflammatory or pro-inflammatory effects according to the disease model being investigated. Elevated circulating chemerin was recently found in patients with inflammatory bowel disease （IBD）; however, the role of chemerin in intestinal inflammation remains unknown. In this study, we demonstrated that the administration of exogenous chemerin （aa 17-156） aggravated the severity of dextran sulfate sodium （DSS）-induced colitis, which was characterized by higher clinical scores, extensive mucosal damage and significantly increased local and systemic production of pro-inflammatory cytokines, including IL-6, TNF-a and interferon （IFN-7）. Interestingly, chemerin did not appear to influence the magnitudes of inflammatory infiltrates in the colons, but did result in significantly decreased colonic expression of M2 macrophage-associated genes, including Arginase 1 （Arg-1）, Yml, FIZZ1 and IL-IO, following DSS exposure, suggesting an impaired M2 macrophage skewing in vivo. Furthermore, an in vitro experiment showed that the addition of chemerin directly suppressed M2 macrophage-associated gene expression and STAT6 phosphorylation in IL-4-stimulated macrophages. Significantly elevated chemerin levels were found in colons from DSS-exposed mice and from ulcerative colitis （UC） patients and appeared to positively correlate with disease severity. Moreover, the in vivo administration of neutralizing anti-chemerin antibody significantly improved intestinal inflammation following DSS exposure. Taken together, our findings reveal a pro-inflammatory role for chemerin in DSS-induced colitis and the ability of chemerin to suppress the anti-inflammatory M2 macrophage response. Our study also suggests that upregulated chemerin in inflamed colons may contribute to the pathogenesis of IBD.展开更多
文摘Background As two novel adipocytokines, chemerin and apelin play a key role in the pathological process of insulin resistance （IR）, glucose metabolism and obesity, researchers have found that the levels of chemerin and apelin changed significantly in type 2 diabetic patients with obesity, however, the underlying mechanism involved remains unclear. The aim of this study was to investigate whether chemerin and apelin play an important role in the pathophysiologic proceeding of diabetes. Methods This study enrolled 81 newly diagnosed obese type 2 diabetes mellitus （T2DM） patients （T2DM group, n=81）. All the patients were randomly assigned to DM1 group treated with metformin （n=41） and DM2 group treated with pioglitazone （n=40）. After hypoglycemic agents treatment, patients under better blood glucose control were chosen to be given antioxidant treatment. Another 79 subjects without T2DM were recruited as normal control group （NC group）, including 40 subjects （NC1 group） with normal body mass index （BMI） and 39 obese subjects （NC2 group）. Levels of chemerin, apelin, BMI, tumor necrosis factor-α（TNF-α）, homeostasis model assessment of IR （HOMA-IR） and 8-isoprotaglandim F2α（8-iso-PGF2α） were examined at baseline and post-treatment. The relationship between chemerin, apelin and BMI, TNF-α, HOMA-IR, 8-iso-PGF2α was analyzed. Results The baseline levels of chemerin, apelin, TNF-α, HOMA-IR and 8-iso-PGF2α in T2DM group were significantly higher than normal control group （P 〈0.001）. All indices mentioned above were significantly decreased after treatment （P 〈0.05）. In T2DM patients treated with pioglitazone, indices mentioned above except for HOMA-IR, were decreased significantly compared with patients treated with mefformin （P〈0.05）. After antioxidant treatment using lipoic acid, levels of chemerin, apelin, TNF-α and 8-iso-PGF2α were further significantly decreased （P 〈0.05）. Correlation analysis showed that the levels of chemerin and apelin c
基金ACKNOWLEDGEMENTS We thank Dr Hongguang Zhu from the Department of Pathology, Fudan University for his useful advice on the histological analysis. This work was supported by the National Natural Science Foundation of China Grant 81172797 （to RH） and the Program of Shanghai Pujiang Talent 11PJ1400400 （to RH）.
文摘Chemerin is present in various inflammatory sites and is closely involved in tissue inflammation. Recent studies have demonstrated that chemerin treatment can cause either anti-inflammatory or pro-inflammatory effects according to the disease model being investigated. Elevated circulating chemerin was recently found in patients with inflammatory bowel disease （IBD）; however, the role of chemerin in intestinal inflammation remains unknown. In this study, we demonstrated that the administration of exogenous chemerin （aa 17-156） aggravated the severity of dextran sulfate sodium （DSS）-induced colitis, which was characterized by higher clinical scores, extensive mucosal damage and significantly increased local and systemic production of pro-inflammatory cytokines, including IL-6, TNF-a and interferon （IFN-7）. Interestingly, chemerin did not appear to influence the magnitudes of inflammatory infiltrates in the colons, but did result in significantly decreased colonic expression of M2 macrophage-associated genes, including Arginase 1 （Arg-1）, Yml, FIZZ1 and IL-IO, following DSS exposure, suggesting an impaired M2 macrophage skewing in vivo. Furthermore, an in vitro experiment showed that the addition of chemerin directly suppressed M2 macrophage-associated gene expression and STAT6 phosphorylation in IL-4-stimulated macrophages. Significantly elevated chemerin levels were found in colons from DSS-exposed mice and from ulcerative colitis （UC） patients and appeared to positively correlate with disease severity. Moreover, the in vivo administration of neutralizing anti-chemerin antibody significantly improved intestinal inflammation following DSS exposure. Taken together, our findings reveal a pro-inflammatory role for chemerin in DSS-induced colitis and the ability of chemerin to suppress the anti-inflammatory M2 macrophage response. Our study also suggests that upregulated chemerin in inflamed colons may contribute to the pathogenesis of IBD.
