Iron overload is positively associated with diabetes risk. However, the role of iron in adipose tissue remains incompletely understood. Here, we report that transferrin-receptor-1-mediated iron uptake is differentially required for distinct subtypes of adipocytes. Notably, adipocyte-specific transferrin receptor 1 deficiency substantially protects mice from high-fat-diet-induced metabolic disorders. Mechanistically, low cellular iron levels have a positive impact on the health of the white adipose tissue and can restrict lipid absorption from the intestine through modulation of vesicular transport in enterocytes following high-fat diet feeding. Specific reduction of adipocyte iron by AAV-mediated overexpression of the iron exporter Ferroportin1 in adult mice effectively mimics these protective effects. In summary, our studies highlight an important role of adipocyte iron in the maintenance of systemic metabolism through an adipocyte-enterocyte axis, offering an additional level of control over caloric influx into the system after feeding by regulating intestinal lipid absorption.

铁过载与糖尿病风险呈正相关。然而，铁在脂肪组织中的作用仍未完全了解。在这里，我们报告转铁蛋白受体 1 介导的铁摄取对于脂肪细胞的不同亚型是不同的。值得注意的是，脂肪细胞特异性转铁蛋白受体 1 缺陷可显着保护小鼠免受高脂肪饮食引起的代谢紊乱。从机制上讲，低细胞铁水平对白色脂肪组织的健康有积极影响，并且可以通过在高脂肪饮食喂养后调节肠细胞中的囊泡转运来限制肠道对脂质的吸收。AAV 介导的铁输出蛋白 Ferroportin1 在成年小鼠中的过度表达对脂肪细胞铁的特异性减少有效地模拟了这些保护作用。总之，