Effects of β-hydroxybutyrate treatment on glycogen repletion and its related signaling cascades in epitrochlearis muscle during 120 min of postexercise recovery

We investigated the effects of beta-hydroxybutyrate (beta-HB), the most abundant type of ketone body in mammals, on postexercise glycogen recovery in skeletal muscle by using an in vitro experimental model. Male ICR mice swam for 60 min and then their epitrochlearis muscles were removed and incubated with either physiological levels of glucose (8 mmol/L) and insulin (60 mu U/mL) or glucose and insulin plus 1, 2, or 4 mmol/L of sodium beta-HB. Four millimoles per liter beta-HB had a significant positive effect on glycogen repletion in epitrochlearis muscle at 120 min after exercise (p < 0.01), while 2 mmol/L of beta-HB showed a tendency to increase the glycogen level (p < 0.09), and 1 mmol/L of beta-HB had no significant effect. We further investigated the effect of 4 mmol/L beta-HB treatment on the signaling cascade related to glycogen repletion in the epitrochlearis muscles throughout a 120-min recovery period. After incubating the muscles in 4 mmol/L of beta-HB for 15 min postexercise, the Akt substrate of 160 kDa Thr(642) (p < 0.05) and Akt Thr(308) (p < 0.05) phosphorylations were significantly increased compared with the control treatment. At the same time point, 5'-AMP-activated protein kinase and acetyl-coenzyme A carboxylase phosphorylations were significantly lower (p < 0.05) in the epitrochlearis muscle incubated with 4 mmol/L of beta-HB than in the control muscle. Our results demonstrate that postexercise 4 mmol/L beta-HB administration enhanced glycogen repletion in epitrochlearis muscle. Four millimoles per liter beta-HB treatment was associated with alternation of the phosphorylated status of several proteins involved in glucose uptake and metabolic/energy homeostasis at the early stage of postexercise.