Department of Physical Medicine and Rehabilitation, Mayo Clinic Graduate School of Biomedical Sciences, Rochester, MN 55905, United States of America; Rehabilitation Medicine Research Center, Department of Physiology and Biomedical Engineering, Mayo Clinic Graduate School of Biomedical Sciences, Rochester, MN 55905, United States of America.
Department of Physical Medicine and Rehabilitation, Mayo Clinic Graduate School of Biomedical Sciences, Rochester, MN 55905, United States of America.
Neurobiol Dis. 2020 Jul;141:104934. doi: 10.1016/j.nbd.2020.104934. Epub 2020 May 4.
A diet high in fat and sucrose (HFHS), the so-called Western diet promotes metabolic syndrome, a significant co-morbidity for individuals with spinal cord injury (SCI). Here we demonstrate that the spinal cord of mice consuming HFHS expresses reduced insulin-like growth factor 1 (IGF-1) and its receptor and shows impaired tricarboxylic acid cycle function, reductions in PLP and increases in astrogliosis, all prior to SCI. After SCI, Western diet impaired sensorimotor and bladder recovery, increased microgliosis, exacerbated oligodendrocyte loss and reduced axon sprouting. Direct and indirect neural injury mechanisms are suggested since HFHS culture conditions drove parallel injury responses directly and indirectly after culture with conditioned media from HFHS-treated astrocytes. In each case, injury mechanisms included reductions in IGF-1R, SIRT1 and PGC-1α and were prevented by metformin. Results highlight the potential for a Western diet to evoke signs of neural insulin resistance and injury and metformin as a strategy to improve mechanisms of neural neuroprotection and repair.
高脂肪和蔗糖饮食（HFHS），即所谓的西方饮食，会促进代谢综合征，这是脊髓损伤（SCI）患者的一种严重合并症。在这里，我们证明了摄入 HFHS 的小鼠的脊髓表达减少的胰岛素样生长因子 1（IGF-1）及其受体，并表现出三羧酸循环功能受损、PLP 减少和星形胶质细胞增生增加，所有这些都发生在 SCI 之前。SCI 后，西方饮食会损害感觉运动和膀胱恢复，增加小胶质细胞增生，加剧少突胶质细胞损失和减少轴突发芽。由于 HFHS 培养条件下的条件培养基可直接和间接引起 HFHS 处理的星形胶质细胞的类似损伤反应，因此提出了直接和间接的神经损伤机制。在每种情况下，损伤机制包括 IGF-1R、SIRT1 和 PGC-1α 的减少，并且都可以通过二甲双胍预防。研究结果强调了西方饮食可能引发神经胰岛素抵抗和损伤的潜在风险，以及二甲双胍作为改善神经保护和修复机制的一种策略。
