A Western diet impairs CNS energy homeostasis and recovery after spinal cord injury: Link to astrocyte metabolism

A diet high in fat and sucrose (HFHS), the so-called Western diet promotes metabolic syndrome, a significant comorbidity 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.