A Compared Study of Gentle Ketogenic Diet Containing Medium-Chain Triglycerides or Long-Chain Triglycerides on Chronic Sleep Deprivation-Induced Cognitive Deficiency in Mice

Ketogenic diet (KD) is well known for its neuroprotective effect, but little is known about its prophylactic efficacy against chronic sleep deprivation (SD) induced cognitive deficiency. Emerging study indicated that ferroptosis plays an important role in neurologic diseases but has been rarely reported in SD. Here, we investigated the prophylactic effects of medium-chain triglycerides enriched KD (MKD) and long-chain triglycerides enriched KD (LKD) on cognitive deficiency and revealed the underlying mechanism focus on the ferroptosis in chronic SD model mice. Results showed that MKD exhibited stronger effects than LKD on improving cognitive deficiency via suppressing ferroptosis and improving synaptic plasticity. Further mechanism results indicated that MKD produced higher Sirt3 protein levels than LKD, which probably contributed to the synergistic effect of beta hydroxybutyric acid and decanoic acid. Our finds provide novel evidence for KD as a safe and feasible dietary intervention to prevent chronic SD induced cognitive deficiency, and suggested a better choice of medium-chain fatty acid enriched KD.