The Hibernation Continuum: Physiological and Molecular Aspects of Metabolic Plasticity in Mammals

(Uploaded by Plazi for the Bat Literature Project) Mammals are often considered to be masters of homeostasis, with the ability to maintain a constant internal milieu, despite marked changes in the envi-ronment; however, many species exhibit striking physiological and biochem-ical plasticity in the face of environmental fluctuations. Here, we review metabolic depression and body temperature fluctuation in mammals, with a focus on the extreme example of hibernation in small-bodied eutherian spe-cies. Careful exploitation of the phenotypic plasticity of mammals with met-abolic flexibility may provide the key to unlocking the molecular secrets of orchestrating and surviving reversible metabolic depression in less plastic species, including humans. In birds and mammals, endothermy is defined as an increase of resting or routine oxygen consump-tion that is ϳ5-to 15-fold higher than that ob-served in similar sized ectotherms (89). The result of this increased metabolism is an increased body temperature (T b). Conversely, decreased metabo-lism is accompanied by reduced T b . Modification of the thermoregulatory setpoint in mammals al-lows for control of both T b and metabolism (29); when the setpoint is lowered to approach an am-bient temperature that is below T b , both metabo-lism and T b decrease. Hibernation lies at the extreme end of a broad spectrum of phenotypes in endotherms that conserve energy by lowering me-tabolism and hence T b (FIGURE 1). Slow-wave sleep is considered the most shallow form of metabolic depression and is common to all mammals (4). T b is only slightly depressed (FIGURE 2A), and oxygen consumption is reduced just 10-15% in this state (95). Torpor is a deeper form of metabolic depression that can be ex-pressed in a variety of patterns. In daily torpor, core T b is usually moderately depressed below 33°C for relatively short periods of time, e.g., Ͻ24 h (FIGURE 2B). In the white-footed mouse, Peromys-cus leucurus, effective daily torpor use can result in an energetic savings of 74% (85). The most extreme form of metabolic depression in mammals occurs during deep hibernation (FIGURE 2C), as exempli-fied by small-bodied, temperate-zone species from a wide range of taxa (reviewed in Refs. 7, 70). In some hibernators, oxygen consumption decreases to as low as 1% of active rates and T b to as low as Ϫ2.9°C (2), leading to a seasonal energy savings of as much as 90% (88). Historically, some authors have used the term estivation to describe torpor bouts that are longer than 1 day (characteristic of hibernation) but occur in warm dry periods rather than in the cold (93). As our knowledge of the thermoregulatory and activity patterns of different mammalian species increases (reviewed in Refs. 21, 22), so does our appreciation of the extent of their metabolic flexibility. At this point, it is important to attempt to dispel some of the confusion surrounding the nomencla-ture of hibernation and torpor. Some of this con-fusion may be the result of the diversity of metabolic strategies underlying torpor use and of hibernation patterns. Most authors refer to torpor as a physiologically controlled depression of met-abolic rate and activity. Torpor initiates with a regulated lowering of heart, respiratory, and met-abolic rates as well as T b setpoint, which allows T b to approach ambient temperature (FIGURE 2, B AND C). After a period of low metabolic activity and stable, but lowered T b , the animal elevates heart, respiratory, and metabolic rates to initiate rewarming and restoration of active T b , recovering from torpor (FIGURE 2B).