Elevated Systemic Hepcidin and Iron Depletion in Obese Premenopausal Females
Elevated Systemic Hepcidin and Iron Depletion in Obese Premenopausal Females
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DOI：
10.1038/oby.2009.319
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发表时间：
2010-07-01
期刊：
影响因子：
6.9
通讯作者：
Braunschweig, Carol
中科院分区：
文献类型：
--
作者：
Tussing-Humphreys, Lisa M.;Nemeth, Elizabeta;Braunschweig, Carol
Hepcidin是机体对全身铁稳态的主要调节因子，在炎症反应中上调，被认为在肥胖人群中观察到的铁缺乏（ID）的表现中起作用。我们测定了绝经前肥胖和非肥胖妇女（n = 20/组）血红蛋白（Hb）匹配的全身hepcidin水平及其与体重、炎症、红细胞生成和铁状态的关系。肥胖参与者也有肝脏和腹部内脏和皮下脂肪组织评估组织铁积累和hepcidin mRNA表达。尽管Hb水平相似，但与非肥胖妇女相比，肥胖妇女血清hepcidin （88.02 vs. 9.70 ng/ml; P < 0.0001）和血清转铁蛋白受体（sTfR） （P = 0.001）显著高于非肥胖妇女。在肥胖女性中，hepcidin与血清铁（r = -0.02）、转铁蛋白饱和度（r = 0.17）或sTfR （r = -0.12）无关；非肥胖者与Tsat （r = 0.70）和血清铁（r = 0.58）呈显著正相关，与sTfR呈负相关（r = -0.63）。在肥胖妇女的肝脏和腹部脂肪组织中可检测到的铁积累很少。肝脏hepcidin mRNA表达量是脂肪组织生成量的700倍，与循环hepcidin水平高度相关（r = 0.61）。尽管铁缺乏，但肥胖妇女血清hepcidin升高，这表明它是对炎症而不是铁状态的反应。过量hepcidin的来源似乎是肝脏而不是脂肪组织。肥胖主要是一种真正的身体缺铁的情况，而不是由炎症引起的铁分布失调。然而，这些发现表明炎症可能通过hepcidin介导的饮食铁吸收抑制而使这种情况持续下去。
Hepcidin, the body's main regulator of systemic iron homeostasis, is upregulated in response to inflammation and is thought to play a role in the manifestation of iron deficiency (ID) observed in obese populations. We determined systemic hepcidin levels and its association with body mass, inflammation, erythropoiesis, and iron status in premenopausal obese and nonobese women (n = 20/group) matched for hemoglobin (Hb). The obese participants also had liver and abdominal visceral and subcutaneous adipose tissue assessed for tissue iron accumulation and hepcidin mRNA expression. Despite similar Hb levels, the obese women had significantly higher serum hepcidin (88.02 vs. 9.70 ng/ml; P < 0.0001) and serum transferrin receptor (sTfR) (P = 0.001) compared to nonobese. In the obese women hepcidin was not correlated with serum iron (r = -0.02), transferrin saturation (Tsat) (r = 0.17) or sTfR (r = -0.12); in the nonobese it was significantly positively correlated with Tsat (r = 0.70) and serum iron (r = 0.58), and inversely with sTfR (r = -0.63). Detectable iron accumulation in the liver and abdominal adipose tissue of the obese women was minimal. Liver hepcidin mRNA expression was similar to 700 times greater than adipose tissue production and highly correlated with circulating hepcidin levels (r = 0.61). Serum hepcidin is elevated in obese women despite iron depletion, suggesting that it is responding to inflammation rather than iron status. The source of excess hepcidin appears to be the liver and not adipose tissue. The ID of obesity is predominantly a condition of a true body iron deficit rather than maldistribution of iron due to inflammation. However, these findings suggest inflammation may perpetuate this condition by hepcidin-mediated inhibition of dietary iron absorption.