Hemojuvelin: A New Link Between Obesity and Iron Homeostasis
Hemojuvelin: A New Link Between Obesity and Iron Homeostasis
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DOI：
10.1038/oby.2011.12
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发表时间：
2011-08-01
期刊：
影响因子：
6.9
通讯作者：
Bekri, Soumeya
中科院分区：
文献类型：
--
作者：
Luciani, Nathalie;Brasse-Lagnel, Carole;Bekri, Soumeya
脂肪组织可能在系统性铁调节中发挥积极作用，这种作用可能是肥胖患者的决定性因素。事实上，我们之前报道了hepcidin，铁调节激素，在脂肪组织中表达，其信使RNA （mRNA）表达在病态肥胖患者的脂肪组织中增加。本研究的目的是表征病态肥胖患者脂肪组织中另一种铁调节蛋白-血幼蛋白（HJV）的状态。由于细胞相关的HJV作为骨形态发生蛋白（BMP）的辅助受体增强肝细胞中hepcidin的表达，我们研究了脂肪组织中这一途径可能参与调节hepcidin表达的可能性。研究HJV在病态肥胖患者脂肪组织中的表达。评估可溶性HJV血药浓度。在体外培养的脂肪细胞中研究了Hepcidin在BMP通路中的调控作用。HJV在脂肪组织中mRNA和蛋白水平均有表达。在肥胖患者脂肪组织中，其mRNA表达量高，且与mRNA hepcidin表达水平相关。有趣的是，脂肪组织表达的HJV可能是有效的，因为培养的脂肪细胞在通过Smad效应物受到BMP2攻击时增加了hepcidin的表达。可溶性HJV血药浓度显著升高。综上所述，脂肪组织可能通过表达主要铁调节蛋白影响肥胖患者的铁稳态，BMP信号通路可能参与调节该组织中hepcidin的表达。
The adipose tissue may play an active role in systemic iron regulation and this role may be determinant in obese patients. Indeed, we reported previously that hepcidin, the iron-regulatory hormone, is expressed in adipose tissue and its messenger RNA (mRNA) expression is increased in adipose tissue of morbidly obese patients. The objectives of this study were to characterize the status of hemojuvelin (HJV), another iron-regulatory protein, within the adipose tissue of morbidly obese patients. Since cell-associated HJV acts as a coreceptor of bone morphogenetic protein (BMP) to enhance hepcidin expression in liver cells, we investigated the possible involvement of this pathway in adipose tissue in regulating hepcidin expression. HJV expression was studied in adipose tissue of morbidly obese patients. Soluble HJV blood concentrations were assessed. Hepcidin regulation through BMP pathway was investigated in cultured adipocytes. HJV was expressed both at mRNA and protein levels in adipose tissue. Moreover, its mRNA expression was highly increased in adipose tissue of obese patients and correlated with mRNA hepcidin expression levels. Interestingly, HJV expressed by adipose tissue may be effective since cultured adipocytes increased their hepcidin expression when challenged with BMP2 through Smad effectors. In addition, blood concentrations of soluble HJV were significantly increased. In conclusion, adipose tissue may influence iron homeostasis in obese patients by expressing major iron-regulatory proteins and the BMP signaling pathway could be involved in regulating hepcidin expression in this tissue.