Inhibition of daily torpor in mice requires calories, not just feeding: a potential role for GLP-1.

Torpor is an energy-saving physiological state characterized by a drop in the metabolic rate of the animal, followed by a decrease in core body temperature. In mice, daily torpor can be avoided through food consumption, but it remains unclear whether this effect is due to the physical presence of food in the digestive system or the caloric content of the meal. We hypothesized that physical digestion or distension is sufficient to prevent torpor, even in the absence of calories. To test this, C57Bl/6J female mice were implanted with temperature telemeters and calorically restricted until they consistently entered torpor. These mice were then given ad libitum access to either caloric gelatin or very low-calorie (VLC) gelatin diet (0.05 kcal/g). Mice that consumed the VLC diet continued to enter torpor, whereas consumption of caloric gelatin prevented torpor. Further, daily torpor was blocked by consumption of any of the caloric macromolecules: carbohydrates, fats, or proteins. We next investigated whether this caloric effect was mediated by gut hormones. Circulating glucagon-like peptide 1 (GLP-1) was relatively low in mice given the VLC diet (when torpor occurred) and elevated during caloric feeding (when torpor was inhibited). Administration of liraglutide, a GLP-1 receptor agonist, prevented calorically-restricted mice from entering torpor. Together these data suggest that GLP-1 mediates the suppression of daily torpor in the mouse in response to the input of calories from a meal.