Traumatic brain injury and obesity induce persistent central insulin resistance

Traumatic brain injury (TBI)‐induced impairments in cerebral energy metabolism impede tissue repair and contribute to delayed functional recovery. Moreover, the transient alteration in brain glucose utilization corresponds to a period of increased vulnerability to the negative effects of a subsequent TBI. In order to better understand the factors contributing to TBI‐induced central metabolic dysfunction, we examined the effect of single and repeated TBIs on brain insulin signalling. Here we show that TBI induced acute brain insulin resistance, which resolved within 7 days following a single injury but persisted until 28 days following repeated injuries. Obesity, which causes brain insulin resistance and neuroinflammation, exacerbated the consequences of TBI. Obese mice that underwent a TBI exhibited a prolonged reduction of Akt (also known as protein kinase B) signalling, exacerbated neuroinflammation (microglial activation), learning and memory deficits, and anxiety‐like behaviours. Taken together, the transient changes in brain insulin sensitivity following TBI suggest a reduced capacity of the injured brain to respond to the neuroprotective and anti‐inflammatory actions of insulin and Akt signalling, and thus may be a contributing factor for the damaging neuroinflammation and long‐lasting deficits that occur following TBI. Traumatic brain injury significantly increases the energy demand on the brain in order to repair damaged tissue, resulting in metabolic dysfunction and increasing vulnerability to subsequent brain injury. Here, we present evidence that repeated traumatic brain injury induces long‐lasting central insulin resistance. Moreover, obesity‐induced central insulin resistance exacerbates inflammation after TBI, and adversely affects TBI‐induced cognitive and affective deficits.