Isonitrogenous low-carbohydrate diet elicits specific changes in metabolic gene expression in the skeletal muscle of exercise-trained mice.

With the renewed interest in low-carbohydrate diets (LCDs) in the sports field, a few animal studies have investigated their potential. However, most rodent studies have used an LCD containing low protein, which does not recapitulate a human LCD, and the muscle-specific adaptation in response to an LCD remains unclear. Therefore, we investigated the effects of two types of LCDs, both containing the same proportion of protein as a regular diet (isonitrogenous LCD; INLCD), on body composition, exercise performance, and metabolic fuel selection at the genetic level in the skeletal muscles of exercise-trained mice. Three groups of mice (n = 8 in each group), one fed a regular AIN-93G diet served as the control, and the others fed either of the two INLCDs containing 20% protein and 10% carbohydrate (INLCD-10%) or 20% protein and 1% carbohydrate (INLCD-1%) had a regular exercise load (5 times/week) for 12 weeks. Body weight and muscle mass did not decrease in either of the INLCD-fed groups, and the muscle glycogen levels and endurance capacity did not differ among the three groups. Only in the mice fed INLCD-1% did the plasma ketone concentration significantly increase, and gene expression related to glucose utilization significantly declined in the muscles. Both INLCD-1% and INLCD-10% consumption increased gene expression related to lipid utilization. These results suggest that, although INLCD treatment did not affect endurance capacity, it helped maintain muscle mass and glycogen content regardless of the glucose intake restrictions in trained mice. Moreover, an INLCD containing a low carbohydrate content might present an advantage by increasing lipid oxidation without ketosis and suppressing muscle glucose utilization.