GLP-1R agonist blocks torpor in mice while GLP-1R deletion does not disrupt normal torpor behavior

Torpor is a low metabolic state seen in many animals induced by calorie deficit and prevented by food intake in mice. One hormone involved in caloric intake regulation that is released during a meal is glucagon-like peptide-1 (GLP-1). The role of GLP-1 in modulating torpor during a caloric deficit is unclear. We hypothesized that a GLP-1 receptor agonist would prevent torpor in wild-type mice, and further, that mice missing the GLP-1 receptor (GLP-1R) would exhibit earlier entry into torpor and prolonged torpor bouts. To test these hypotheses, GLP-1R-/- mice and litter mate controls were implanted with heart rate (HR)/body temperature (Tb) telemeters and subjected to 1) baseline ad libitum feeding, 2) caloric restriction (2 g/day) for 7 days to induce torpor, fed at the onset of the dark phase, and 3) injected intraperitoneally with a GLP-1R agonist (semaglutide 10nmol/kg) on a caloric restriction day. During the baseline period, litter mate controls had a HR of 538±14 bpm and Tb of 36.6±0.2°C that was not significantly different from GLP-1R-/- mice (536±17 bpm, 36.8±0.1°C, p >0.05 for both comparisons). During the caloric restriction period all mice entered torpor. GLP-1R-/- mice entered torpor with the same latency as litter mate controls (623±113, 620±99 min, respectively relative to the onset of feeding, p >0.05). The duration of torpor (time spent below 29°C) was 272±82min in wild-type controls, and not significantly different in GLP-1R-/- mice (281±115 min, p >0.05). The depth of torpor was also not significantly different between litter mate controls and GLP-1R-/- mice (23.6±1.8, 22.4±1.0˚C, respectively, p >0.05). Mice then received a semaglutide injection (10nmol/kg) at the onset of the dark phase during caloric restriction. Semaglutide blocked torpor in litter mate control mice (min Tb = 31.5±1.3˚C) with no time spent under 29˚C, whereas torpor was not blunted in GLP-1R-/- mice as expected (min Tb = 22.4±0.9˚C, p< 0.05 v. control; time under 29˚C = 359±83 min). These data support the hypothesis that GLP-1R agonism blocks caloric-restriction induced torpor in the mouse. However, the GLP-1R is not required for normal torpor behavior as the torpor characteristics–latency, depth, and duration–of GLP-1R-/- mice closely resemble those of litter mate controls. Data shown as mean ± sd. This study was funded internally by Williams College. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.