Clocks and meals keep mice from being cool

Abstract

Daily torpor is used by small mammals to reduce daily energy expenditure in response to energetic challenges. Optimizing the timing of daily torpor allows mammals to maximize its energetic benefits and, accordingly, torpor typically occurs in the late night and early morning in most species. However, the regulatory mechanisms underlying such temporal regulation have not been elucidated. Direct control by the circadian clock and indirect control through the timing of food intake have both been suggested as possible mechanisms. Here, feeding cycles outside of the circadian range and brain-specific mutations of circadian clock genes ( ; ) were used to separate the roles of the circadian clock and food timing in controlling the timing of daily torpor in mice. These experiments revealed that the timing of daily torpor is transiently inhibited by feeding, while the circadian clock is the major determinant of the timing of torpor. Torpor never occurred during the early part of the circadian active phase, but was preferentially initiated late in the subjective night. Food intake disrupted torpor in the first 4-6 h after feeding by preventing or interrupting torpor bouts. Following interruption, re-initiation of torpor was unlikely until after the next circadian active phase. Overall, these results demonstrate that feeding transiently inhibits torpor while the central circadian clock gates the timing of daily torpor in response to energetic challenges by restricting the initiation of torpor to a specific circadian phase.

The relationship between fasting-induced torpor, sleep, and wakefulness in laboratory mice

“…Interestingly, under a restricted feeding schedule, mice enter torpor predominantly in the dark phase, during which they are typically active in laboratory conditions, whereas the opposite is mostly true for torpor triggered by shortening of the photoperiod. This is consistent with previous studies of fasting-induced torpor in mice [ 49 , 62 , 88 ], but further work is necessary to disentangle the roles of the endogenous clock, the timing of feeding and the degree of energetic challenge in torpor initiation and its other characteristics [ 89 , 90 ].…”

Impact of endogenous melatonin on rhythmic behaviors, reproduction, and survival revealed in melatonin‐proficient C57BL/6J congenic mice

“…60,61 They appear to be complex mechanisms composed of pivotal neurons in the preoptic area in the hypothalamus and connected to several systems associated with circadian rhythms, thyroid hormone-dependent photoperiodicity, and feeding behavior. 62,63 Melatonin signaling is closely related to these physiological systems: for example, melatonin receptors (MT 1 and MT 2 ) are F I G U R E 8 Restricted feeding-induced daily torpor in AH−/− and AH+/+ mice. A, Representative body temperature recordings of female mice subjected to 7-d restricted feeding.…”

Turn it off and on again: characteristics and control of torpor

“…When mice are unable to access sufficient calories to maintain active physiology and normal body temperature, they will enter periods of torpor lasting several hours ( Hudson & Scott, 1979 ). Stimuli for torpor in mice include acute fasting ( Sunagawa & Takahashi, 2016 ), a combination of fasting and reduction in the ambient temperature ( Hitrec et al ., 2019 ; Swoap & Gutilla, 2009 ), food restriction ( van der Vinne et al ., 2018 ), or simply increasing the energy costs of foraging ( Schubert et al ., 2010 ). This latter observation supports the hypothesis that it is a relative imbalance of energy supply compared to the demands of maintaining ‘normal’ physiological homeostasis rather than a response to cold and hunger per se, which triggers torpor.…”

“…Torpor in mice generally occurs during the latter part of the lights off period ( Brown & Staples, 2010 ; Webb et al ., 1982 ). Timing of torpor entry is primarily under the control the circadian clock, but can be adjusted by the timing or expected timing of food ( van der Vinne et al ., 2018 ), or entrained to food in mice or hamsters lacking endogenous circadian clocks ( Paul et al ., 2004 ; van der Vinne et al ., 2018 ). Duration of torpor in mice is inversely proportional to the weight of the mouse ( Hudson & Scott, 1979 ), with some evidence that torpor is engaged when food restriction or fasting decreases body weight to approximately 20g ( Solymár et al ., 2015 ), although this experiment was performed only in male mice.…”

“…As well as playing a role in thermoregulation ( Jeong et al ., 2015 ; Liedtke, 2017 ; Zhao et al ., 2017 ), the DMH also adjusts circadian rhythms based on the timing of food availability ( Gooley et al ., 2006 ). One might speculate that the dorsomedial hypothalamus integrates information about the availability and timing of food in order to optimise the timing of torpor, which is known to be under circadian control but can be adjusted according to food availability ( van der Vinne et al ., 2018 ).…”