Traumatic brain injury alters hepatic gluconeogenic metabolism assessed using hyperpolarized pyruvate

A recent study reveals that traumatic brain injury triggers a distinct metabolic response in the liver, as determined through the use of hyperpolarized 13C-pyruvate. This method allows for the assessment of crucial enzymatic activities involved in liver metabolism. The research, conducted on rats with controlled cortical impact, involved monitoring hepatic metabolism under both fed and fasted conditions three to four days post-injury.

The study evaluated various hyperpolarized 13C products, including [13C]bicarbonate, [5-13C]glutamate, [1-13C]acetyl-L-carnitine, and [2-13C]phosphoenolpyruvate to gauge mitochondrial and gluconeogenic metabolism.

Under fasted conditions following brain injury, the research found an increase in [13C]bicarbonate and [2-13C]phosphoenolpyruvate, indicating an upregulation of the hepatic gluconeogenic pathway. Additionally, analysis of liver tissue extracts from injured rats using NMR isotopomer analysis showed an elevated [2,3-13C2]glutamate-to-[4,5-13C2]glutamate ratio and increased 13C-labeling in phosphoenolpyruvate compared to control samples.

These findings confirm that the hepatic gluconeogenic pathway is enhanced in response to traumatic brain injury. The researchers conclude that this study demonstrates the potential of using hyperpolarized pyruvate to monitor the acute phase response of the liver to brain injuries in real-time, which could be valuable for tracking immunometabolic changes during pathogenesis and therapeutic interventions.