Increased adipose tissue expression of hepcidin in severe obesity is independent from diabetes and NASH
Increased adipose tissue expression of hepcidin in severe obesity is independent from diabetes and NASH
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DOI：
10.1053/j.gastro.2006.07.007
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发表时间：
2006-09-01
期刊：
影响因子：
29.4
通讯作者：
Le Marchand-Brustel, Yannick
中科院分区：
文献类型：
--
作者：
Bekri, Soumeya;Gual, Philippe;Le Marchand-Brustel, Yannick
背景与目的：铁调素是一种急性时相反应肽。我们已经研究了铁调素可能参与大规模肥胖，慢性低度炎症的状态。研究了三组严重肥胖的患者，有或没有糖尿病或非酒精性脂肪性肝炎。方法：检测肝硬化患者肝脏和脂肪组织中Hepcidin的表达。通过脂肪组织外植体刺激研究在体外研究铁调素调节。结果：Hepcidin不仅在肝脏中表达，而且在脂肪组织中也有表达。此外，肥胖患者脂肪组织中的mRNA表达增加。糖尿病或NASH的存在没有改变肝和脂肪组织中的铁调素表达水平。在脂肪组织中，mRNA表达与炎症指数、白细胞介素-6和C反应蛋白相关。白细胞介素-6也促进体外hepcidin的表达。68%的肥胖患者存在低转铁蛋白饱和度，此外，这些患者中有24%出现贫血。观察到的铁状态的变化可能是由于铁调素作为肠道铁吸收和巨噬细胞铁流出的负调节剂的作用。有趣的是，与低转铁蛋白饱和度相关的铁调素表达的反馈控制机制发生在肝脏中，而不是脂肪组织中。结论：Hepcidin是一种促炎性脂肪因子，在肥胖状态下炎症性低铁血症中可能起重要作用。
Backgrounds & Aims: Hepcidin is an acute-phase response peptide. We have investigated the possible involvement of hepcidin in massive obesity, a state of chronic low-grade inflammation. Three groups of severely obese patients with or without diabetes or nonalcoholic steatohepatitis were investigated. Methods: Hepcidin expression was studied in liver and adipose tissue of these patients. Hepcidin regulation was investigated in vitro by adipose tissue explant stimulation studies. Results: Hepcidin was expressed not only in the liver but also at the messenger RNA (mRNA) and the protein levels in adipose tissue. Moreover, mRNA expression was increased in adipose tissue of obese patients. The presence of diabetes or NASH did not modify the hepcidin expression levels in liver and adipose tissue. In adipose tissue, mRNA expression correlated with indexes of inflammation, interleukin-6, and C-reactive protein. Interleukin-6 also promoted in vitro hepcidin expression. A low transferrin saturation ratio was observed in 68% of the obese patients; moreover, 24% of these patients presented with anemia. The observed changes in iron status could be due to the role of hepcidin as a negative regulator of intestinal iron absorption and macrophage iron efflux. interestingly, a feedback control mechanism on hepcidin expression related to low transferrin saturation occurred in the liver but not in the adipose tissue. Conclusions: Hepcidin is a proinflammatory adipokine and may play an important role in hypoferremia of inflammation in obese condition.