Circadian regulation of the lactate metabolic kinetics in mice using the [ 1 H- 13 C]-NMR technique

Abstract

Abstract Lactate is not only the energy substrate of neural cells, but also an important signal molecule in brain. In modern societies, disturbed circadian rhythms pose a global challenge. Therefore, exploring the influence of circadian period on lactate and its metabolic kinetics is essential for the advancement of neuroscientific research. In the present study, mice were infused [3-13C] lactate through the tail vein for a duration of two minutes. After 30 minutes lactate metabolism, the animals were sacrificed and the brain tissue was extracted and tested. And then the [1H-13C] NMR technology was employed to investigate the kinetic information of lactate metabolism in different brain regions during various time periods and acute sleep deprivation, to detect the enrichment of various neurochemicals. The results revealed fluctuating lactate concentrations in the brain throughout the day, with lower levels during light periods and higher levels during dark periods. Most metabolites displayed strong sensitivity to circadian rhythm, exhibiting significant day-night variations. Conversely, only a few metabolites showed changes after acute sleep deprivation, primarily in the temporal brain region. Interestingly, in contrast to brain lactate metabolism, liver lactate metabolism exhibited a significant increase following acute sleep deprivation. This study explored the kinetics of lactate metabolism, hinted at potential clinical implications for disorders involving circadian rhythm disturbances, and providing a new research basis for clinical exploration of brain lactate metabolism.