Thermogenic changes with chronic cold exposure in the naked mole-rat (Heterocephalus glaber)

Abstract

The naked mole-rat (Heterocephalus glaber) lives communally in a thermally buffered underground habitat. Here, it relies primarily on ectothermic (behavioral) mechanisms to maintain body temperature (T_b). Outside this milieu, it is unable to effectively regulate T_b and T_b tracks that of ambient temperature (T_a). Although naked mole-rats, in their natural habitat have little need for cold-tolerance, we questioned whether or not thermogenic capacity would change with prolonged (>1 year) exposure to cooler conditions. We hypothesized that these rodents would not conform to common mammalian patterns and that non-shivering thermogenic (NST) capacity would be unchanged with chronic cold exposure. The capacity for NST was assessed following noradrenaline administration (0.8 mg/kg, s.c.) to lightly anesthetized (pentobarbital 6% m/v 40 mg/kg) animals and monitoring the concomitant changes in oxygen consumption and T_b. Results concur with the null hypothesis in that prolonged cold exposure did not elicit any increase in NST capacity (1.52±0.17 ml O₂/g/h, cold-acclimated; 1.73±0.31 ml O₂/g/h, control; P>0.05). Rapid heat loss across their uninsulated integument may necessitate continuous maximal stimulation of brown adipose tissue (BAT), and as such, prevent any further increase in thermogenic capacity following cold exposure.

Introduction

Non-shivering thermogenesis is commonly employed in response to acute cold stress in small mammals living in both tropical and temperate areas (Heldmaier, 1993, Haim et al., 1998, Li et al., 2001). However, adaptive changes in the capacity for non-shivering thermogenesis (NST) are critical for the survival of small mammals in temperate environments where pronounced seasonal differences in ambient temperature (T_a) prevail (Hayes, 1989, Heldmaier, 1993, Haim and Izhaki, 1993, Nespolo et al., 2001). Endogenous heat production via sympathetically mediated NST is enhanced in response to cold, thus compensating for increased heat loss to the environment (Williams, 1968, Hissa and Hirsimaki, 1971). Brown adipose tissue (BAT) is the major site for this sympathetic-induced NST response (Foster and Frydman, 1978, Foster and Frydman, 1979, Carneheim et al., 1984, Himms-Hagen, 1990). An acute cold stimulus increases thermogenesis in existing BAT, whilst chronic cold exposure markedly increases the capacity for NST via proliferation and neural recruitment of BAT (Himms-Hagen, 1990). As such the NST response of non-hibernating rodents following chronic cold exposure is commonly 1.5-fold greater than the maximal induced NST response prior to cold exposure (Wunder and Gettinger, 1996).

Naked mole-rats (Heterocephalus glaber) are hairless rodents, unable to effectively regulate body temperature (T_b), such that despite the employment of endogenous thermogenic mechanisms (e.g. NST and shivering) these mammals thermoconform to their environment (Buffenstein and Yahav, 1991, Hislop and Buffenstein, 1994). These atypical mammalian features reflect the evolutionary history and lifestyle of naked mole-rats; these animals live in large colonies in a thermally buffered underground habitat in tropical North East Africa (Lavocat, 1978, Jarvis, 1981, Brett, 1991, Buffenstein, 1996). In their natural milieu there is little need to be cold-tolerant and naked mole-rats are able to rely of ectothermic mechanisms (such as huddling and thigmothermy) to maintain a constant T_b. When these animals are housed in the laboratory under simulated burrow temperatures of 31–32 °C, and subjected to acute variations in T_a, metabolism increases by more than 50% over basal levels for every 1 °C drop in T_a below ‘apparent thermoneutrality’ (as T_b is never regulated) till approximately 29 °C (Buffenstein and Yahav, 1991). At this comparatively warm temperature rates of heat production relative to basal metabolic rate (BMR) are of similar magnitude to those exhibited by other cold-stressed laboratory rodents at an T_a of approximately 5 °C (Dicker et al., 1995, Hammond et al., 1996).

Naked mole-rats appear to be extremely sensitive to prolonged exposure to cooler conditions and respond with marked changes in thermoregulatory profiles (Woodley, 2000), thyroid hormone concentrations (Buffenstein et al., 2001), lung morphology (Maina et al., 2001) and reproductive function (Woodley, 2000). These animals react to prolonged cold exposure in a similar manner to that shown by most mammals: Food consumption is 1.4-fold greater and BMR is elevated (Woodley, 2000) suggesting that average daily energy expenditure is raised. Furthermore, these animals exhibit a ‘left shift’ in the metabolism/temperature rate curves, such that the lower critical temperature of the ‘apparent thermoneutral zone’ (TNZ) is decreased; the TNZ is extended from 31–34 to 27–34 °C, and the slope of RMR/T_a is reduced (Woodley, 2000). These features minimize energy expenditure under cold conditions (Cossins and Bowler, 1987). Peak metabolism in that study (Woodley, 2000) was of a similar magnitude to that previously noted under various conditions (Buffenstein and Yahav, 1991, Hislop and Buffenstein, 1994, Urison and Buffenstein, 1995), implying that maximal metabolic rate was unchanged, and that naked mole-rats may not be able to (or might not choose to) adjust their endothermic capacity and thus may be unresponsive to chronic cold conditions. We investigated whether or not, these animals respond to prolonged cold-stress by increasing BAT thermogenic capacity by monitoring changes in oxygen consumption (Vo₂) and T_b following noradrenaline (NA) intervention.