Glucose metabolic responses to psychological stress vary across developmental stages in mice

Cyclic vomiting syndrome (CVS) with acetonemia is a representative psychosomatic disorder triggered by psychological stress. In most cases, patients experience symptoms of ketoacidosis, including vomiting during childhood, which typically resolve by approximately 10 years of age. Although abnormal activation of the glucose metabolic response associated with stress has been suggested to be involved in its onset, the underlying mechanisms remain unclear. In this study, we established a mouse model of stress-induced glycogen depletion and ketosis observed in CVS with acetonemia. We compared the glucose metabolic responses to stress between young (4-week-old) and adult (8-week-old) mice. After 8 h of restraint stress (RS), liver glycogen levels decreased in both age groups. At 16 h post-stress, liver glycogen levels recovered to the baseline level in adult mice, but did not recover in young mice. This difference was attributed to a significant reduction in food intake in young mice owing to stress. Furthermore, young mice exhibited a marked elevation in blood ketone levels during RS, suggesting that an immature stress response induced lipolysis. This experimental model may help to elucidate how immature stress responses contribute to metabolic dysregulation. This study is a step toward understanding the pathology of CVS with acetonemia.