Type 2 diabetes mellitus (T2DM) and insulin resistance (IR) have been associated with dysregulation of iron metabolism. The basis for this association is not completely understood. To attempt to investigate this, we studied temporal associations between onset of insulin resistance (IR) and dysregulated iron homeostasis, in a mouse model of T2DM.

Male C57Bl/6 mice (aged 8 weeks) were fed a high-fat diet (HFD; 60% energy from fat) or a control diet (CD; 10% energy from fat) for 4, 8, 12, 16, 20 and 24 weeks. Development of IR was documented, and various metabolic, inflammatory and iron-related parameters were studied in these mice.

HFD-feeding induced weight gain, hepato-steatosis and IR in the mice. Onset of IR occurred from 12 weeks onwards. Hepatic iron stores progressively declined from 16 weeks onwards. Accompanying changes included a decrease in hepatic hepcidin (Hamp1) mRNA expression and serum hepcidin levels and an increase in iron content in the epididymal white adipose tissue (eWAT). Iron content in the liver negatively correlated with that in the eWAT. Factors known to regulate hepatic Hamp1 expression (such as serum iron levels, systemic inflammation, and bone marrow-derived erythroid regulators) were not affected by HFD-feeding. In conclusion, the results show that the onset of IR in HFD-fed mice preceded dysregulation of iron homeostasis, evidence of which were found both in the liver and visceral adipose tissue.

2 型糖尿病 (T2DM) 和胰岛素抵抗 (IR) 与铁代谢失调有关。这种关联的基础尚不完全清楚。为了尝试对此进行研究，我们在 T2DM 小鼠模型中研究了胰岛素抵抗 (IR) 发作与铁稳态失调之间的时间关联。

雄性 C57Bl/6 小鼠（8 周龄）在 4、8、12、16、20 和 4、8、12、16、20 和24 周。记录了 IR 的发展，并在这些小鼠中研究了各种代谢、炎症和铁相关参数。

HFD 喂养诱导小鼠体重增加、肝脂肪变性和 IR。从 12 周开始出现 IR。肝铁储备从 16 周开始逐渐下降。伴随的变化包括肝铁调素 ( Hamp1 ) mRNA 表达和血清铁调素水平的降低以及附睾白色脂肪组织 (eWAT) 中铁含量的增加。肝脏中的铁含量与 eWAT 中的铁含量呈负相关。已知调节肝Hamp1的因素表达（如血清铁水平、全身炎症和骨髓来源的红细胞调节剂）不受 HFD 喂养的影响。总之，结果表明，在 HFD 喂养的小鼠中，IR 的发作先于铁稳态的失调，在肝脏和内脏脂肪组织中都发现了这种失调的证据。