Moreno-Navarrete José María, Ortega Francisco, Moreno María, Ricart Wifredo, Fernández-Real José Manuel
Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi), Hospital of Girona 'Dr Josep Trueta', Girona, Spain.
Diabetologia. 2014 Sep;57(9):1957-67. doi: 10.1007/s00125-014-3298-5. Epub 2014 Jun 29.
AIMS/HYPOTHESIS: Adipose tissue from obese and insulin-resistant individuals showed altered expression of several iron-related genes in a recent study, suggesting that iron might have an important role in adipogenesis. To investigate this possible role, we aimed to characterise the effects of iron on adipocyte differentiation.
Intracellular iron deficiency was achieved using two independent approaches: deferoxamine administration (20 and 100 μmol/l) and transferrin knockdown (TF KD). The effects of added FeSO4, holo-transferrin and palmitate were studied during human and 3T3-L1 adipocyte differentiation. Finally, the relationship between iron-related and mitochondrial-related genes was investigated in human adipose tissue.
Most adipose tissue iron-related genes were predominantly expressed in adipocytes compared with stromal vascular cells. Of note, transferrin gene and protein expression increased significantly during adipocyte differentiation. Both deferoxamine and TF KD severely blunted adipocyte differentiation in parallel with increased inflammatory mRNAs. These effects were reversed in a dose-dependent manner after iron supplementation. Palmitate administration also led to a state of functional intracellular iron deficiency, with decreased Tf gene expression and iron uptake during adipocyte differentiation, which was reversed with transferrin co-treatment. On the other hand, iron in excess impaired differentiation, but this antiadipogenic effect was less pronounced than under iron chelation. Of interest, expression of several genes involved in mitochondrial biogenesis occurred in parallel with expression of iron-related genes both during adipogenesis and in human adipose tissue.
CONCLUSIONS/INTERPRETATION: Precise and fine-tuned iron availability is essential to achieve optimal adipocyte differentiation, possibly modulating adipocyte mitochondrial biogenesis.
目的/假设：在最近一项研究中，肥胖和胰岛素抵抗个体的脂肪组织显示出几种铁相关基因的表达改变，这表明铁可能在脂肪生成中起重要作用。为了研究这一可能的作用，我们旨在表征铁对脂肪细胞分化的影响。
使用两种独立的方法实现细胞内铁缺乏：给予去铁胺（20和100μmol/l）和敲低转铁蛋白（TF KD）。在人类和3T3-L1脂肪细胞分化过程中，研究添加硫酸亚铁、全转铁蛋白和棕榈酸的影响。最后，在人类脂肪组织中研究铁相关基因和线粒体相关基因之间的关系。
与基质血管细胞相比，大多数脂肪组织铁相关基因主要在脂肪细胞中表达。值得注意的是，在脂肪细胞分化过程中，转铁蛋白基因和蛋白表达显著增加。去铁胺和TF KD均严重抑制脂肪细胞分化，同时炎症mRNA增加。补充铁后，这些作用以剂量依赖的方式逆转。给予棕榈酸也导致细胞内功能性铁缺乏状态，脂肪细胞分化过程中转铁蛋白基因表达和铁摄取减少，转铁蛋白共同处理可逆转这种情况。另一方面，铁过量会损害分化，但这种抗脂肪生成作用不如铁螯合时明显。有趣的是，在脂肪生成过程中和人类脂肪组织中，参与线粒体生物发生的几个基因的表达与铁相关基因的表达同时发生。
结论/解读：精确且微调的铁可用性对于实现最佳脂肪细胞分化至关重要，可能会调节脂肪细胞线粒体生物发生。
