Brain Trauma Disrupts Hepatic Lipid Metabolism: Blame It on Fructose?

Scope The action of brain disorders on peripheral metabolism is poorly understood. The impact of traumatic brain injury (TBI) on peripheral organ function and how TBI effects can be influenced by the metabolic perturbation elicited by fructose ingestion are studied. Methods and Results It is found that TBI affects glucose metabolism and signaling proteins for insulin and growth hormone in the liver; these effects are exacerbated by fructose ingestion. Fructose, principally metabolized in the liver, potentiates the action of TBI on hepatic lipid droplet accumulation. Studies in isolated cultured hepatocytes identify GH and fructose as factors for the synthesis of lipids. The liver has a major role in the synthesis of lipids used for brain function and repair. TBI results in differentially expressed genes in the hypothalamus, primarily associated with lipid metabolism, providing cues to understand central control of peripheral alterations. Fructose‐fed TBI animals have elevated levels of markers of inflammation, lipid peroxidation, and cell energy metabolism, suggesting the pro‐inflammatory impact of TBI and fructose in the liver. Conclusion Results reveal the impact of TBI on systemic metabolism and the aggravating action of fructose. The hypothalamic‐pituitary‐growth axis seems to play a major role in the regulation of the peripheral TBI pathology. Traumatic brain injury (TBI) and fructose acutely affect hepatic function. TBI and fructose alter peripheral glucose metabolism and liver function by involving the hypothalamic–pituitary–growth hormone axis and affecting growth hormone production and growth hormone receptors function. TBI and fructose potentiate lipid deposition and promote a pro‐inflammatory and dysfunctional metabolic stage in the liver, which strikes back on the brain and exacerbates TBI pathophysiology.