Postexercise ketone monoester administration concomitant with glucose stimulates glycogen repletion in soleus muscle in mice

Abstract

Although our group has demonstrated that the administration of β-hydroxybutyrate, a major type of ketone body, stimulated postexercise glycogen repletion in isolated skeletal muscle, investigations of the effects of ketone supplementation on postexercise muscle glycogen repletion in vivo have obtained conflicting results. Here, we investigated the effects of an oral intake of the ketone monoester [(R)-3-hydroxybutyl (R)-3-hydroxybutyrate] on postexercise glycogen repletion in mouse skeletal muscles. Ten-week-old male Institute of Cancer Research mice ran on a treadmill at 25 m/min speed for 60 min. Immediately after the exercise, the mice were orally administered a solution containing 1.0 g/kg body wt (BW) of glucose and 2.0 g/kg BW of ketone monoester (KE solution) or a solution containing glucose and 1.11 g/kg BW of triolein for the adjustment of total calories to match the KE solution's (Con solution). The KE-treated group showed significantly lower postadministration blood glucose concentrations and higher plasma insulin concentrations compared with those of the Con-treated group. The KE-treated group showed a 42.1% higher glycogen concentration in soleus muscle (slow-twitch fiber-dominant) at 60 min postadministration compared with that of the Con group. There was no significant between-group difference in the glycogen concentration in the plantaris muscle (fast-twitch fiber-dominant). The KE-treated group's soleus muscle also showed significantly lower phosphorylation levels of AMP-activated kinase Thr¹⁷² at 30 min postexercise compared with the level immediately postexercise. These results demonstrated that a postexercise administration of ketone monoester enhanced glycogen repletion, particularly in slow-twitch fiber-dominant muscle.NEW & NOTEWORTHY This is the first study to compare the effects of postexercise ketone body intake on glycogen repletion in fast-twitch fiber- and slow-twitch fiber-dominant muscles. A postexercise administration of ketone monoester together with glucose enhanced the glycogen repletion in murine slow-twitch fiber-dominant muscle but not in fast-twitch fiber-dominant muscle. The ketone monoester intake also elicited higher insulin levels in plasma and lower AMPK phosphorylation levels in soleus muscle during the postexercise phase.

Keywords: AMP-activated kinase; glycogen repletion; insulin; ketone monoester; skeletal muscle.