Energetics of fasting heterothermia in TRPV1-KO and wild type mice

Abstract

To learn the possible role of TRPV1 in the changes of temperature regulation induced by short-term energy lack, TRPV1-KO and wild type mice were exposed to complete fasting for 2 or 3 days while their core temperature and locomotor activity were recorded using a biotelemetry method. In both types of mice, fasting led to progressive daytime hypothermia with night-time core temperature being maintained at normothermia (collectively called heterothermia). During fasting rises of locomotor activity were observed parallel to night-time normothermia with occasional increases of both parameters recorded every 2 to 3 hours (ultradian rhythms). The daytime fall of core temperature was significantly greater in wild type than in TRPV1-KO mice, in the former an advance of the temperature/activity rhythm having been observed in spite of the presence of a 12/12 hour light/darkness schedule. Re-feeding applied at the beginning of the light-period led to rapid reappearance of normothermia in both types of mice without a large increase in locomotor activity. It is concluded that the TRPV1-gene may have a role in the development of adaptive daytime hypothermia (and hence saving some energy) in mice during complete fasting but still allowing normothermia maintained at night, a strategy probably serving survival under natural conditions in small size rodents such as the mouse. The possible role of muscle thermogenesis either with or without gross bodily movement during fasting or on re-feeding, respectively, may be based on different mechanisms yet to be clarified.

Introduction

Since the characterization of TRPV1, the first thermoreceptor identified at molecular level [4], there has been a growing interest to learn a possible role of this receptor in thermoregulation, in general [3], [18], [34] and in fever, in particular [16]. Although TRPV1 is known to be activated by supraphysiologal heat under in vitro circumstances, the decreased physiological heat defence observed in TRPV1-knockout (TRPV1-KO) mice [34] may indicate a more complex role of this receptor in thermoregulation. The finding that under basic conditions TRPV1-KO mice have more pronounced circadian core temperature amplitude than their wild type (WT) counterparts [34] makes it likely that in energetic situations characterized by an exaggerated day–night core temperature amplitude, as e.g. in fasting [8], [22], [38], an altered thermoregulatory response may be observed in TRPV1-KO mice.

Experimental data supporting a general role of TRPV receptors in thermoregulation have been reported more recently. In particular, non-thermal stimuli have been shown to inhibit cold-defence mechanisms by TRPV1 receptors in rats [31], since pharmacological blockade of these receptors resulted in an attenuation of the hyperthermic effect of capsaicin or resiniferatoxin, stimulants of TRPV1-receptors. Those authors have concluded that tonic activation of TRPV1 channels by yet unidentified non-thermal factors inhibited skin vasoconstriction and thermogenesis, thus possessing a suppressive effect on body core temperature. On this basis it could be supposed that a non-thermal stimulus such as fasting may also lead to an attenuated hypothermic response in animals devoid of functional TRPV1 receptors.

In the present studies changes of body core temperature and locomotor activity were monitored in TRPV1-KO and wild type mice during fasting and on re-feeding by biotelemetry. Although temporary hypothermia as a response to fasting has been known for some time [22], [38], the possible energetic background of night normothermia has not been studied so far. The monitoring of locomotor activity was believed to shed some light on the possible role of physical activity in body temperature regulation, an issue having been debated in animal studies [see [9], [12], [13]].