Role of Ketone bodies in muscle anabolism and catabolism during exercise and training

Ketone bodies are molecules present in minimal amounts in blood under physiological conditions. Their increment is associated with fasting and high-fat diet. Ketone bodies can replace glucose as an energy source in muscle and brain. Since for skeletal muscle their utilization can provide a readily available alternative to glucose, we hypothesize that ketone bodies administration can stimulate metabolic reprogramming of muscles. However this potential has not yet been investigated, mainly because increased blood ketone levels in general are associated with severe side effects. Recently, the synthesis of a well-tolerated ketone body ester, i.e. (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (3HHB), allowed to increase plasma ketone bodies to levels occurring during fasting, yet without the side effects of high fat diet.

We aim to study the effects of 3HHB supplementation on muscular plasticity during exercise or pathological degeneration. In part 1 of this project we study the role of 3HHB administration in muscle repair after strenuous exercise in healthy volunteers. In part 2 we look at the long-term effects of 3HHB administration on muscular adaptation during a 6-week high-intensity training period. Finally, we study the effects of 3HHB in muscle degeneration in a murine model of cancer cachexia. We want to provide innovative data on the role of ketone bodies in cellular and molecular processes involved in muscle anabolism and catabolism during training.