Oral β-GPA induces daily torpor in the mouse

In response to caloric deficit and a cool environment, mice ( Mus musculus Linnaeus, 1758) employ daily torpor, a physiological state characterized by metabolic rate depression and bradycardia, followed by a decrease in body temperature. Although some heat is generated during arousal from torpor via uncoupling-protein 1 (UCP1)-dependent activity, there is also evidence of UCP1-independent mechanisms. We hypothesized that mice utilize futile creatine cycling as a UCP1-independent mechanism for generating heat during arousal from torpor, and thus interference with this cycle would result in longer arousal times. β-Guanidinopropionic acid (β-GPA), a creatine analog shown to decrease cellular creatine levels, was used to assess the role of the futile creatine cycle in arousal from torpor. Mice consuming a standard 1% β-GPA diet lost body weight and, unexpectedly, experienced drops in body temperature that appear “torpor-like” in nature. Behavioral (body position) and physiological (body temperature dynamics, heart rate dynamics and variability, surface tail temperature) assessments were used to distinguish between torpor-like bouts induced by 1% β-GPA feeding and natural torpor. Our analysis suggests that the torpor-like bouts induced during feeding of 1% β-GPA should be considered daily torpor. Contrary to our initial hypothesis, the rate of arousal from these bouts was not significantly affected by β-GPA treatment. Still, the utilization of torpor by mice in a fed state is an unusual finding, and one of the few cases where food consumption does not inhibit daily torpor in the mouse.