Metabolic responses to physiological stressors assessed using continuous glucose monitoring integrated with indirect calorimetry in mice

Abstract

Continuous glucose monitoring (CGM) in rodents has provided unprecedented temporal resolution of glycemic dynamics in vivo. Even in the absence of deliberate perturbation, glucose levels in mice are dynamic, fluctuating in response to the timing and duration of feeding events, changes in neurological and hormonal states, physical activity, and photoperiod. To obtain a comprehensive view of metabolic adaptations under common experimental conditions, we monitored freely moving mice simultaneously using CGM and indirect calorimetry to quantify glucose, food intake, physical activity and metabolic rate. We characterized glycemic and metabolic responses to routine laboratory interventions, including short-term and overnight fasting, refeeding, tail blood sampling during glucose tolerance tests, changes in ambient temperature to cold or thermoneutral conditions, and access to running wheels. We found that food removal induced a robust, transient stress response characterized by increased blood glucose, body temperature, energy expenditure, and physical activity. However, prolonged fasting ultimately led to hypoglycemia and torpor. The magnitude and variability of glycemic responses to insulin tolerance tests were strongly influenced by fasting duration, and tail-tip blood collection itself elicited substantial hyperglycemia. In contrast to prolonged fasting, refeeding produced relatively modest and transient effects on glucose and energy expenditure. Cold exposure elicited increased energy expenditure along with a sustained hyperglycemic response. Voluntary wheel running induced transient increases in glucose and metabolic activity and promoted a shift toward increased fatty acid oxidation. Together, these findings demonstrate that common laboratory manipulations exert dynamic, often substantial effects on glycemia and whole-body metabolism that are readily revealed by CGM and indirect calorimetry.