Abstract：
Iron deposition and myelin loss are observed in the brain with aging, and iron accumulation is suggested to be involved in myelin damage. However, the exact mechanism of iron deposition with aging remains unclear. This study was aimed to determine whether expanded visceral adipose tissue contributes to iron deposition and myelin loss by inducing hepcidin in the brains of aged male mice. Compared with young adult mice, levels of hepcidin in the brain, epididymal adipose tissue, and circulation were increased in aged mice, which had expanded visceral adipose tissue with inflammation. An increase in expressions of ferritin, an indicator of intracellular iron status, was accompanied by decreased levels of proteins related to myelin sheath in the brains of aged mice. These age-related changes in the brain were improved by visceral fat removal. In addition, IL-6 level, activation of microglia/macrophages, and nuclear translocation of phosphorylated Smad1/5 (pSmad1/5) inducing hepcidin expression were reduced in the brains of aged mice after visceral fat removal, accompanied by decreases of pSmad1/5- and ferritin-positive microglia/macrophages and mature oligodendrocytes. These findings indicate that visceral adiposity contributes to hepcidin-mediated iron deposition and myelin loss with inflammation in the aged brain. Our results support the importance of preventing visceral adiposity for maintaining brain health in older individuals.
摘要：
随着衰老，在大脑中观察到铁沉积和髓鞘丢失，铁的积累与髓鞘损伤有关。然而,铁老化沉积的确切机制尚不清楚。这项研究旨在确定扩大的内脏脂肪组织是否通过在老年雄性小鼠的大脑中诱导铁调素而导致铁沉积和髓磷脂损失。与年轻的成年小鼠相比，大脑中铁调素的水平，附睾脂肪组织,老年小鼠的血液循环增加，内脏脂肪组织扩张并伴有炎症。铁蛋白表达的增加，细胞内铁状态的指标，伴随着老年小鼠大脑中与髓鞘相关的蛋白质水平降低。内脏脂肪去除改善了大脑中与年龄相关的变化。此外,IL-6水平,小胶质细胞/巨噬细胞的激活，和核转位的磷酸化Smad1/5（pSmad1/5）诱导hepcidin表达减少后老年小鼠的大脑内脏脂肪去除，伴随着pSmad1/5-和铁蛋白阳性小胶质细胞/巨噬细胞和成熟少突胶质细胞的减少。这些发现表明，内脏肥胖有助于hepcidin介导的铁沉积和髓鞘丢失，并伴有老年大脑的炎症。我们的结果支持预防内脏肥胖对维持老年人大脑健康的重要性。
