The effect of exercise training in a cold environment on thermoregulation in adult and aged C57BL/6J mice

We studied the effect of exercise training in cold environment (six weeks of daily, one-hour runs on a treadmill at ambient temperature of 6 ± I°C at 60±65% of VO_2max) on cold-induced metabolic heat production, heat loss, and cold tolerance in adult and aged C57BL/6J male mice. In adult mice, exercise training in cold environment resulted in greater cold-induced heat production and cold tolerance without changes in heat loss, similar to the effects of daily cold exposure without exercise. In aged mice, daily cold exposures did not affect cold tolerance and cold-induced heat production, but exercise training in the cold resulted in greater cold-induced heat production and cold tolerance. Heat loss in aged mice increased similarly after both repeated cold exposures and exercise training in the cold. Therefore, mechanisms of effect of exercise training on cold tolerance are different in adult and aged animals. Exercise training in cold environment does not affect cold-induced heat production and cold tolerance in adult mice, but improves them in aged animals.     

Metabolic heat production during repeated testing at 24 degrees C and 6 degrees C in adult and aged male C57BL/6J mice: the effect of physical restraint before cold stress

Adult (9-14 month) and aged (29-31 month) male C57BL/6J mice were subjected to 3 baseline tests (BASE), 3 cold tests (COLD), or 3 baseline immediately followed by cold tests (BASE/COLD). All tests consisted of partial restraint, and baseline tests were at 24 degrees C for 1 h while cold tests were at 6 degrees C for 3 h. All tests were started at 0900 and were repeated every 2 weeks. Mice were weighed before each test and colonic temperature, O2 consumption, and CO2 production were measured every 4 min for the duration of the test. Mean metabolic heat production during baseline and/or cold and slopes of colonic temperature over time during cold were calculated for each animal. Metabolic heat production at 24 degrees C in both BASE and BASE/COLD was the same in aged mice as adults, however, at degrees C BASE/COLD adult mice increased metabolic heat production compared to 24 degrees C, while aged mice produced a similar amount of heat at both 6 degrees C and 24 degrees C. When comparing metabolic heat production at 6 degrees C between COLD and BASE/COLD mice, adult COLD mice demonstrate an habituation to repeated cold exposure accompanied by increasing heat production, while BASE/COLD adults produce higher heat in all 3 cold exposures. The authors suggest that this is due to a priming of heat production in adults by restraint before the cold. In aged mice, neither COLD nor BASE/COLD groups demonstrate habituation, but BASE/COLD mice produce more heat than COLD during cold exposure, again indicating baseline priming of heat production. The data imply that aged mice have an impairment in specific cold-induced thermogenesis, while their abilities to produce heat in response to restraint-induced sympathetic activation remains intact.     

Nonshivering thermogenesis in adult and aged C57BL/6J mice housed at 22°C and at 29°C

Twelve- and 28-month-old C57BL/6J male mice were housed either at room temperature of 22°C or at thermoneutrality (29°C) during the two months prior to experiments. Acute experiments were conducted under anesthesia, myorelaxation, and artificial ventilation. We recorded efferent electrical impulse activity in one of the sympathetic nerves innervating the interscapular brown adipose tissue in response to acute cold stimulation, when body temperature was lowered 7.5°C below control level. In separate experiments we measured O₂ consumption and CO₂ production and calculated the nonshivering thermogenesis. We also measured the concentration of uncoupling protein in interscapular brown adipose tissue before and after three-hour cold stress. In aged mice, both sympathetic nervous activity and nonshivering thermogenesis were lower in animals housed at thermoneutrality (29°C) than in mice housed at 22°. Among mice maintained at 22°C, but not at thermoneutrality, aged animals had greater nonshivering thermogenesis and greater cold induced concentration of uncoupling protein in the brown adipose tissue than adults. Sympathetic nervous outflow to brown adipose tissue was always greater in aged mice, regardless of the temperature of acclimation. We concluded that aged mice, housed at 22°C, showed the changes in nonshivering thermogenesis associated with cold acclimation. However, an increased sympathetic outflow to brown adipose tissue in aged animals reflects an age-related elevation of the tone and responsiveness of the sympathetic nervous system.     

The effect of exercise training in cold on shivering and nonshivering thermogenesis in adult and aged C57BL/6J mice

To understand the mechanisms of improvement of cold-induced heat production in aged mice following exercise training, the relative contributions of shivering and nonshivering thermogenesis to cold-induced metabolic responses were assessed in adult and aged C57BL/6J male mice, which inhabited sedentarily at room temperature, or were subjected either to a regimen of moderate intensity exercise training at 6°C, or to sedentary repeated exposures to the same temperature. The main findings were that (1) aged mice had greater cold-induced nonshivering thermogenesis, but lower shivering than adult mice; (2) exercise training in a cold environment enhanced cold-induced nonshivering thermogenesis in adult mice, but suppressed it in aged animals; (3) exercise training in a cold environment increased shivering thermogenesis in both age groups, but this increase was much greater in aged mice; (4) the increase of cold-induced shivering thermogenesis was mainly responsible for increased cold tolerance in aged mice after exercise training in a cold environment.     

Nonshivering thermogenesis during acute cold exposure in adult and aged C57BL/6J mice

In C57BL/6J adult and aged mice, housed at room temperature (22.5 ± 1°C), we measured O₂ consumption and CO₂ production and calculated metabolic heat production under conditions of anesthesia and myorelaxation during acute cold stimulation when body temperature was lowered 7.5°C below control level. An independent group of mice was subjected to a three hour partial physical restraint at 6°C and concentration of uncoupling protein (thermogenin) was measured in interscapular brown adipose tissue mitochondria at different times after cold exposure. Heat production under anesthesia and myorelaxation was about 57–66% lower than in nonanesthetized conditions, but increased significantly during cold stimulation in both age groups. Under anesthesia and myorelaxation before and during cold stimulation aged mice produced about 20% more heat than adult mice. Because in these experiments all sources of facultative thermogenesis, except nonshivering, were suppressed by anesthesia and myorelaxation, and because brown adipose tissue is the major source of nonshivering thermoproduction, we concluded that aged mice housed at room temperature have an increased thermogenesis in brown adipose tissue. This conclusion was also supported by the finding that the concentration of uncoupling protein measured in the mitochondria of brown adipose tissue after single cold exposure was significantly higher in aged than in adult mice. Therefore, we propose that the lower, cold-induced, heat production typically observed in nonanesthetized aged mice may reflect reduced thermogenic capacity of skeletal muscles. While aged mice have less brown adipose tissue than adult animals, the remaining brown adipose tissue may compensate by increasing the concentration of uncoupling protein.     

A longitudinal study of tolerance to cold stress among C57BL/6J mice

C57BL/6J male mice of different ages were movement-restricted and exposed to 10 degrees C for 3-hr periods every other week while colonic temperature was measured. A longitudinal trend in cold tolerance related to age and to initial colonic temperature was demonstrated. Adaptative thermoregulatory changes during cold exposure occurred during the first two tests. These were similar for all age groups except 30-month-old mice. There was no adaptation of colonic temperature during cold exposure among aged mice with repeated testing; however, their baseline colonic temperatures prior to testing increased after the first two tests. This finding suggests that old animals adjust to repeated cold stress differently than do younger mice. Specifically, younger animals are capable of adjusting their thermoregulatory response during cold stress with no change in baseline (pre-stress) temperature. Old animals do not modify the responses emitted during the stress; however, they do adapt by raising their baseline temperatures. Repeated cold exposure started later in life increased mortality among old animals but did not affect maximum lifespan.     

Heat loss during cold exposure in ADULT and AGED C57BL/6J mice

Metabolic heat production (MHP), colonic temperature (Tco), and nonevaporative (dry) heat loss were measured in ADULT and AGED C57BL/6J male mice during cold exposure. Dry heat loss was assessed as a differential temperature (Td) between incoming and outgoing air through the chamber for indirect calorimetry. The average Td during cold exposure normalized to surface area for ADULT mice was significantly higher than that for the AGED animals (0.0618 ± 0.0003°C/cm² and 0.0553 ± 0.0005°C/cm², respectively). Linear regression analysis showed that at the same Tco AGED mice showed lower values of Td normalized to surface area, indicating that at the same body temperature they were losing less heat than ADULT animals. It was concluded that age-related decline in cold tolerance in mice is not due to a lack of ability to reduce heat loss during cold exposure. On the contrary, AGED animals had lower heat loss in comparison with ADULT. We suggest that augmentation of heat conservation mechanisms is an adaptive response to diminishing cold-induced heat production.     

Cold-induced metabolism and brown fat GDP binding in young and old rats

The attenuated thermogenic responses observed in older animals exposed to low environmental temperatures may reflect decreased thermogenic capacity of brown adipose tissue, a major nonshivering thermogenic effector in rats, and/or decreased metabolic capacity of lean body mass. to evaluate these possibilities, the oxygen consumption of female Sprague-Dawley rats aged 5 and 26 months was recorded at rest and during 6 h of exposure to 6°C. The thermogenic capacity of brown fat was estimated from the binding of guanosine-5′-diphosphate (GDP) to isolated brown fat mitochondria. Both resting and cold-induced oxygen consumption expressed on a mass independent basis [ml/(min x kg body mass^·67)] and as a function of lean body mass [ml/(min x g lean body mass)] were significantly lower in the 26-month-old animals. Colonic temperatures of younger and older rats after the 6 h of cold exposure were 37.5 ± 0.1 and 36.1 ± 0.2°C, respectively, and were significantly different. However, no significant differences in the binding of GDP to isolated brown fat mitochondria were observed. These data indicate that the thermogenic capacity of brown fat is not decreased in the aged rat, and that the metabolic capacity as well as the amount of lean body mass is altered with age.     

Effect of intermittent feeding on thermoregulatory abilities of young and aged C57BL/6J mice

At 6 mth of age, male C57BL/6J mice were subjected to an intermittent schedule of feeding (every-other-day) or continued to be maintained on an ad libitum diet (24% protein). This regimen of dietary restriction resulted in increased mean and maximum lifespan (11%) compared to the survival of ad libitum-fed mice. At 8 and 26 mth of age, different groups of mice were tested for cold tolerance during 3 h exposure to 10 degrees C. Aged mice (26 mth) fed ad libitum compared to young mice (8 mth) on the same diet had significantly lower baseline colonic temperatures prior to cold exposure, and impaired cold tolerance, as measured by the rate of decline in colonic temperature during cold exposure. Dietary restriction by intermittent feeding had no significant effect on cold tolerance in young mice or baseline colonic temperature in young or aged mice. However, the cold tolerance of aged mice subjected to 20 mth of intermittent feeding was markedly improved over that of aged cohorts maintained on an ad libitum diet and in fact was indistinguishable from that of young counterparts. Thus, it appeared that this regimen of dietary restriction when implemented in young adults prevented the age-related decline in cold tolerance observed among ad libitum fed mice of this strain.     

Nasal heat exchange in a northern ungulate, the reindeer (Rangifer tarandus)

When reindeer were exposed to low ambient temperatures, heat and water were recovered from the exhaled air by a nasal counter-current heat exchanger. Measurements of respiratory frequency, minute volume, exhaled air temperature and metabolic rate were made over a range of ambient air temperatures extending from -5.5 degrees C to 27.2 degrees C. At ambient air temperatures less than 10 degrees C the exhaled air temperatures were an average of 21 degrees C less than body temperature. The reduction of the exhaled air temperature at the lowest ambient air temperatures used in this study resulted in the recovery of 75% of the heat added and 80% of the water added to the inspired air on its way to the lungs. The heat and water recovered by the nasal temporal counter-current heat exchanger in reindeer significantly reduced the metabolic cost of survival during cold exposure.     

Energy turnover and heat exchange in mature lean and obese Zucker rats acutely exposed to three environmental temperatures for 24 hours

Differences between lean (FA/?, n = 6) and obese (fa/fa, n = 6) mature male Zucker rats' energy turnover and heat storage were compared during a 24-h period when the animals were exposed to ambient temperatures of 30, 15 or 5 degrees C. Energy turnover was examined through measurements of heat production rates via indirect calorimetry and heat loss rates via direct calorimetry. Heat storage rates were calculated as the difference between heat production and heat loss rates. Predicted heat storage rates were also calculated as the product of the change in core temperature and the calculated specific heat of the animal based on body composition (carcass) analysis. A minimal heat loss rate was determined for each animal representing a period of least activity. Various comparisons were made: between groups (lean/obese), temperature (30, 15, 5 degrees C), calorimetry method (indirect/direct), period (light/dark), heat storage (experimental/predicted), and minimal heat loss. Immediately before a test, pretest weight and colonic temperature were obtained. Then, the animal was placed into the calorimeter chamber and remained there unrestrained for 24 h. Normal light/dark periods were maintained. On removal from the calorimeter, core temperature and body weight measurements were again obtained. Upon completion of all tests, body composition was analyzed and surface area determined. Energy turnover, i.e. both heat production and heat loss in the lean and obese animals differed among the 30, 15 and 5 degrees C exposures. The obese animals had relatively greater heat production rate and heat loss rate (kcal/day or kcal/kg (FFM)/day than the lean animals at 30, 15 and 5 degrees C. But, on a relative basis, the increments in heat production in the cold environments were greater for the lean animals. Both the lean and obese animals tended to be more active during the dark period when at 30 degrees C, but the difference was less at 15 degrees C and even less at 5 degrees C. Experimental heat storage rates did not differ significantly from predicted values at any of the temperatures with the possible exception of the animals at 5 degrees C. It was concluded that the mature obese Zucker rats had no major discernible defect in thermoregulation as revealed by rates of heat production and loss, although three of the obese rats did elicit a drop in colonic temperature during exposure to 5 degrees C, i.e. their excessive subcutaneous adiposity and thermal insulation did not prevent a fall in colonic temperature.(ABSTRACT TRUNCATED AT 400 WORDS)     

Longevity and body weight loss of silkworm moth, Bombyx mori, varied by different temperature treatments

The adult of silkworm, Bombyx mori, has a very short lifetime, since it lives without taking food after emergence. The body weight at emergence took on a seasonal variety, when reared at optimal temperature (25°C); about 1·4 times heavier in spring than in autumn. These were, however, few seasonal differences of the mean and maximum life spans. All metabolisms and the rate of living of silkworm moth appear to be accelerated by such high temperatures as 30 and 35°C, resulting in shortening their life span by 50%. On the contrary, the moths kept at 4°C maintained life approximately five times longer than the moth at optimal temperature. The final body weight level of the moth exposed to cold never fell to the final weight level at the optimal temperature. It might be difficult to account for the elongation of the life span only by a moderate disturbance of metabolic processes at the low temperature. Neither correlations between life span and body weight at emergence nor between life span and body weight at death were recognized by the every temperature treatment. Energy corresponding to about a quarter of body weight at emergence was utilized for basic metabolisms necessary to maintain the minimal life, muscle movements and oviposition at the optimal temperature.

Oviposition of virgin females was promoted by high temperature treatments, but inhibited by low temperature. The ratio of total oviposition days to mean life span was almost comparable between optimal and high temperature conditions. Only at low temperature the ratio was less than that at optimum. During the adult period three increasing phases of death number were observed. Oviposition in females did not seem to be concerned with the second increase phase in the middle ages.     

Thermoregulatory and cardiac responses of infant spontaneously hypertensive and Wistar-Kyoto rats to cold exposure.

Cardiovascular function during cold exposure is dependent on effective thermoregulation. This dependence is particularly apparent in infants. For example, we have previously demonstrated that in infant rats during cold exposure, cardiac rate is directly related to their ability to produce heat endogenously. The primary source of endogenous heat production for infant rats is brown adipose tissue (BAT). Because of the dependence of cardiac rate on effective thermoregulation in the cold and because hypertension in spontaneously hypertensive rats (SHR) is influenced by the preweanling environment, in this study we examined the thermoregulatory and cardiac rate responses of infant SHR and Wistar-Kyoto rats (WKY) to varying levels of cold exposure. In experiment 1, 7- to 8-day-old SHR and WKY were acclimated at a thermoneutral air temperature (35 degrees C) and then exposed to successive decreases in ambient temperature (30.5 degrees C, 26.5 degrees C, 23 degrees C, and 17 degrees C) while thermal and metabolic measures were recorded. Although both strains increased BAT thermogenesis and oxygen consumption in response to cold exposure, SHR cooled more than WKY and exhibited lower levels of oxygen consumption at the lowest air temperatures. Experiment 2 was identical to experiment 1 except that cardiac rate was also measured. Again, SHR exhibited substantial thermoregulatory deficits compared with WKY; in addition, they were less able than WKY to maintain cardiac rate at the 2 lowest air temperatures tested. Finally, in experiment 3, infant SHR exhibited diminished BAT thermogenesis in response to a range of doses of a selective beta3-adrenoceptor agonist. We hypothesize that long-term thermoregulatory deficits during the early postnatal period influence cardiovascular function and contribute to the development of hypertension in SHR.     

Body temperature rhythms, cold tolerance, and fever in young and old rats of both genders

The circadian rhythm of body temperature (CTR) of male and female rats living at 23°C, as well as their body temperature response to a yeast injection or to a 2-h exposure to 0°C, was investigated by telemetry. Young rats had a clear CTR with a mean nocturnal peak of 38.0 ± 0.1°C and diurnal trough of 36.2 ± 0.1°C. Older rats, starting at about 18 months of age, tended to have poor (that is, lower amplitude) rhythms. Mean daily body temperature was 37.1 ± 0.2°C at all ages. After exposure to the cold, the body temperature of young rats, old rats with a strong CTR, and old rats with a poor CTR changed in the ranges of −0.3 to +1.5°C, −3.1 to +0.7°C, and −5.2 to +0.4°C, respectively. This indicates that old animals, especially but not exclusively those with poor CTRs, are less resistant to cold stress. On the other hand, the capacity to develop a fever in response to a yeast injection was equivalent in the three groups of animals, although females had a smaller response than males. It is concluded that the process of aging does not have a generalized debilitating effect on temperature regulation in rats. Rather, aging seems to affect individual components of the thermoregulatory system differentially.     

Acute effects of nicotine on plasma free fatty acid concentrations and on the response to cold stress, in lean and obese (genotype ob/ob) mice

Lean and genetically obese (ob/ob) male and female mice were given nicotine by subcutaneous injection. Nicotine treatment was found to raise plasma free fatty acids by similar amounts in both lean and obese mice. In lean mice, nicotine caused depression of rectal temperature at ambient temperatures 22-25 degrees C and partially prevented the hypothermia in these mice when exposed to cold (o-3 degrees C). In obese mice, nicotine treatment did not alter either rectal temperature at 22-25 degrees C or the severe hypothermia on cold exposure. It is proposed that the effect of nicotine on free fatty acids is due to release of adrenal catecholamines and that this mechanism operates in both lean and obese animals. It is also proposed that, in obese mice under normal circumstances, there is a defect in the central nervous control of this adrenergic mechanism which may contribute to the observed fall in body temperature at low ambient temperatures.     

Breathing in the potassium depleted rat: the role of metabolic rate and body temperature

Rats with dietary potassium (K) depletion have an altered breathing pattern compared to age matched control rats. The K depleted rats also have a decreased body weight gain, basal metabolic rate and body temperature. In this study, age matched controls are underfed (UFC) to match for body weight gain and metabolic rate and controls are exposed to different ambient temperatures to alter metabolism and body temperature. Compared to UFC rats with the same body weight and basal metabolic rate the K depleted rats breathe slower and with a larger tidal volume in the basal state and in response to hypercapnia and hypoxia. With heat stress body temperature is increased in K depleted rats as is metabolic rate. While frequency is increased it is still slower than in controls at the same ambient and body temperatures. We conclude that the low metabolic rate and body temperature of K depleted rats is not the cause of the altered breathing pattern. In addition, it is shown that the hypothermia of K depletion is present only at ambient temperatures below the thermoneutral zone and that is is apparently due to an inability of the K depleted rat to increase metabolic heat production with cold stress.     

Leptin is required for uncoupling protein-1-independent thermogenesis during cold stress

We investigated the role of leptin in regulating energy metabolism through induction of uncoupling protein (UCP)-1-based brown fat thermogenesis by comparing phenotypes of energy balance in ob/ob and double-mutant ob/ob.Ucp1(-/-) mice. Measurements of adiposity and lean body mass (nuclear magnetic resonance), energy expenditure (indirect calorimetry), body weight, food intake, and core body temperature were determined in the two mutant stocks of 3-month-old mice maintained at an initial ambient temperature of 28 C for 21 d and then at 21 C for 16 d, and finally with leptin administration for 8 d at 21 C. No phenotypic differences between ob/ob and ob/ob.Ucp1(-/-) mice were detected, suggesting that UCP1-based thermogenesis is not essential for the regulation of adiposity in ob/ob mice at temperatures between 21 and 28 C. Although both Ucp1(-/-) and ob/ob mice can survive in extreme cold at 4 C, provided they are adapted to the cold by gradually lowering ambient temperature, ob/ob.Ucp1(-/-) mice could not adapt and survive at temperatures lower than 12 C unless they were administered leptin. As the ambient temperature was reduced from 20 to 16 C, ob/ob.Ucp1(-/-) mice treated with leptin have elevated levels of circulating T(3) that correlate with elevated sarcoendoplasmic reticulum Ca(2+) ATPase 2a mRNA levels in gastrocnemius muscle. Furthermore, ob/ob.Ucp1(-/-) mice, treated with T(3), were able to maintain body temperature and stimulate sarcoendoplasmic reticulum Ca(2+) ATPase 2a expression when the ambient temperature was gradually reduced to 4 C. Thus, in the absence of UCP1, leptin-induced thermogenesis protects body temperature in part through its action on the thyroid hormone axis.     

The effect of cold acclimation and exercise training on cold tolerance in aged C57BL/6J mice

We investigated whether intermittent cold acclimation and low intensity exercise training, two interventions known to improve thermoregulatory function in young rodents, enhanced cold tolerance in aged C57BL/6J mice. Mice, aged 18 to 20 months, were randomly assigned to four treatment conditions: (a) intermittent cold acclimation (CA) (50 min per day, 5 times per week for 3 weeks at 5 degrees C), (b) submaximal treadmill exercise (EX) (15 m min-1 for 30 min, 5 times per week for 8 weeks, (c) sequential treatment of CA + EX, and (d) control group. Mice were exposed to a 3-hr cold stress test (15 degrees C) prior to and following treatment. CA aged mice maintained normothermia and demonstrated significant increases in oxygen consumption and brown adipose tissue protein concentration compared with controls; enhanced cold tolerance was probably due to increased utilization of nonshivering thermogenesis. EX aged mice had elevated O2 consumption and increased skeletal muscle enzyme activity compared with controls; however, cold tolerance was not enhanced compared with CA mice. The data suggest that intermittent CA effectively reduces hypothermia during cold challenge in aged mice.     

The effect of acute cold and warm ambient temperatures on the thyroid hormone concentration in blood plasma,blood supply,and oxygen consumption in Japanese quail

Blood supply to the thyroid gland, blood plasma T₄ and T₃ concentration, oxygen consumption, and body temperature were measured in Japanese quail in cold (?1 to ?6°) and warm (34 to 35°) ambient temperatures. The most pronounced changes were noted during the first hour of temperature influence. During this time, in cold ambient temperature, the blood supply of the thyroid and T₃ concentration in the plasma increased 2.14- and 3.24-fold, respectively. The T₄ concentration initially decreased significantly then it increased. In a warm ambient temperature constant decreases in blood supply and T₄ concentration were noted. The plasma T₃ concentration was significant greater at 5 and 48 hr after warm exposure. Oxygen consumption was elevated within the first hour of cold diuration, a decline in oxygen consumption was not observed before Hour 12 of heat influence. A statistically significant change in rectal and skin temperatures occurred chiefly during cold exposure.     

Thermogenesis in diabetes-obesity syndromes in mutant mice

Summary The two mouse mutants, obese (ob) and diabetes (db), cause similar diabetes-obesity syndromes that are characterized by a marked increase in apparent metabolic efficiency with regard to utilization of energy. A failure to thermoregulate in a normal fashion would save energy which could then be diverted to other functions and be reflected as increased metabolic efficiency. This study assesses the contribution of a defect in thermogenesis to the increased metabolic efficiency. Thermogenesis in obese (ob) and diabetes (db) mutant mice was quantified at various environmental temperatures. Both mutants maintained body temperatures near normal when maintained at ambient temperatures (23 °C), and if exposed to cold at 10 °C for a brief period, became cold-adapted and would survive indefinitely at 4°C. Rectal temperatures of mutants maintained at 4 °C were only 1 °–2 °C less than those seen in normal mice. This maintenance of nearly normal body temperature at temperatures less than thermoneutral was reflected by increased food consumption in all mice maintained in the cold. The data presented suggest that the defect in thermogenesis in both mutants is not a major cause of the increased metabolic efficiency. Hyperinsulinaemia, a consistent feature of both mutants, might by increasing anabolic processes (synthesis) and decreasing degradation spare energy normally used for tissue turnover and account for some of this increased metabolic efficiency.