JCI：脂肪细胞铁水平调节脂联素和胰岛素敏感性

铁过载增加产生胰岛素耐受性和患上II型糖尿病的风险，但是连接这两者之间的确切机制仍然是个未知数。

根据发表在Journal of Clinical Investigation期刊上的一篇论文，来自美国犹他大学的Donald McClain和同事们报道，血清铁蛋白水平能够预测人们是否患上代谢综合症(metabolic syndrome)，并且与脂联素(adiponectin)表达呈负相关关系。脂联素是脂肪细胞产生的一种调节血液葡萄糖的蛋白。

利用铁处理脂肪细胞会降低脂联素水平，这就表明脂肪细胞在检测营养和铁中发挥着至关重要的作用。再者，病人血清铁蛋白水平下降能够增加胰岛素敏感性和葡萄糖耐受性。

这项研究着重强调脂肪细胞在代谢疾病中发挥着重要作用，并且指出铁下降可能作为一种治疗糖尿病的方法。

doi: 10.1172/JCI44421
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Adipocyte iron regulates adiponectin and insulin sensitivity

J. Scott Gabrielsen1, Yan Gao1, Judith A. Simcox1, Jingyu Huang1, David Thorup1, Deborah Jones1, Robert C. Cooksey1,2, David Gabrielsen1, Ted D. Adams3, Steven C. Hunt3, Paul N. Hopkins3, William T. Cefalu4 and Donald A. McClain

Iron overload is associated with increased diabetes risk. We therefore investigated the effect of iron on adiponectin, an insulin-sensitizing adipokine that is decreased in diabetic patients. In humans, normal-range serum ferritin levels were inversely associated with adiponectin, independent of inflammation. Ferritin was increased and adiponectin was decreased in type 2 diabetic and in obese diabetic subjects compared with those in equally obese individuals without metabolic syndrome. Mice fed a high-iron diet and cultured adipocytes treated with iron exhibited decreased adiponectin mRNA and protein. We found that iron negatively regulated adiponectin transcription via FOXO1-mediated repression. Further, loss of the adipocyte iron export channel, ferroportin, in mice resulted in adipocyte iron loading, decreased adiponectin, and insulin resistance. Conversely, organismal iron overload and increased adipocyte ferroportin expression because of hemochromatosis are associated with decreased adipocyte iron, increased adiponectin, improved glucose tolerance, and increased insulin sensitivity. Phlebotomy of humans with impaired glucose tolerance and ferritin values in the highest quartile of normal increased adiponectin and improved glucose tolerance. These findings demonstrate a causal role for iron as a risk factor for metabolic syndrome and a role for adipocytes in modulating metabolism through adiponectin in response to iron stores.