Differential effects of hypoxia on sleep of warm- and cold-acclimated rats

We studied the effect of different levels of hypoxia (10, 12 or 13, 15, and 18% O2) on the sleep-waking pattern (SWP) and the maximum-minimum core temperature of warm-acclimated (WA) and cold-acclimated (CA) rats at their neutral temperature, 29 degrees C. Whereas the SWP of WA rats showed a trend toward increasing disruption as the degree of hypoxia increased, CA rats exhibited no such trend. The effect was chiefly on the frequency of state changes and less on epoch durations. The SWP of WA rats was more vulnerable to hypoxia than that of CA rats. Maximum and minimum body temperatures of WA and CA rats were not significantly affected by O2 lack down to 10% inspired O2. We conclude that in the rat 1) hypoxia primarily affects the neural mechanism that governs the frequency of changes in sleep-waking states; 2) the extent of alterations in SWP's depends on the ambient temperature to which the rats are acclimated; and 3) hypoxia does not significantly affect deep body temperature at the animal's neutral temperature.     

Brown fat thermogenesis in cold-acclimated rats is not abolished by the suppression of thyroid function

The effects of long-term cold exposure on brown adipose tissue (BAT) thermogenesis in hypothyroid rats have been examined. Thyroid ablation was performed in normal rats after 2 mo of exposure to 4 degrees C, when BAT hypertrophy and thermogenic activity were maximal. After ablation, hypothyroid and normal controls remained in the cold for 2 additional months. At the end of the 4-mo cold exposure, all untreated hypothyroid rats were alive, had normal body temperature, and had gained an average 12.8% more weight than normal controls. Long-term cold exposure of hypothyroid rats markedly increased BAT weight, mitochondrial proteins, uncoupling protein (UCP)-1, mRNA for UCP-1, and oxygen consumption to levels similar to those seen in cold-exposed normal rats. The results indicate that thyroid hormones are required for increased thermogenic capacity to occur as an adaptation to long-term cold exposure. However, cold adaptation can be maintained in the absence of thyroid hormone.     

Effect of selective and non-selective opioids on body temperature in warm- and cold-acclimated rats

(1) Exposure to ambient temperatures outside the thermoneutral zone modifies energy balance in mammals. (2) This study examined the response of acclimated animals to the administration of non-selective and mu-selective opioid agonists and antagonists on body temperature (T_b). (3) Saline had no effect on T_b. (4) In cold-acclimated animals, naloxone alone decreased T_b while morphine produced a biphasic response. (5) In both warm- and cold-acclimated animals, PL-017 induced hyperthermia. (6) CTAP, had no effect alone and blocked PL-017-induced hyperthermia in both groups of animals. (7) The data shows that acclimation modifies the response of the animals to administration of opioid agonists and antagonists.     

Glycerol uptake by erythrocytes from warm- and cold-acclimated Cope’s gray treefrogs

Cope’s gray treefrogs, Hyla chrysoscelis, accumulate glycerol during the period of cold acclimation that leads to the development of freeze tolerance. Glycerol must cross cell membranes in numerous processes during this time, including exit from hepatocytes where glycerol is synthesized and entry into other tissues, where glycerol is cryoprotective. Thus, we hypothesized that erythrocytes from H. chrysoscelis would be permeable to glycerol and that that permeability would be up-regulated during cold acclimation. Further, we hypothesized that glycerol permeability would be associated with the expression of aquaporins, particularly those from the glyceroporin sub-family. Erythrocytes from warm-acclimated treefrogs had high glycerol permeability at 20°C, as assessed by the time required for osmotic lysis following suspension in 0.2 M glycerol. That osmotic lysis, as well as uptake of radio-labeled glycerol, was inhibited by 0.3 mM HgCl₃. Permeability assessed via osmotic lysis was markedly reduced at 5°C. These properties were similar in animals deriving from northern (Ohio) and southern (Alabama) populations, although suggestive (through statistical interactions) of greater glycerol permeability in northern animals. Erythrocytes expressed mRNA and protein for a previously described glyceroporin, HC-3. In cold-acclimated animals, HC-3 protein expression was up-regulated, but we could not detect a concomitant enhancement of glycerol permeability.     

Role of hyperthyroidism in increased thermogenesis in the cold-acclimated Syrian hamster

The oxygen consumption of cold-acclimated Syrian hamsters (measured in pentobarbital-anaesthetized animals) was 59% greater than that of warm-acclimated hamsters. Upon return of the cold-acclimated hamsters to 24 degrees C, the elevated metabolic rate declined slowly, with half-life of approximately 1 day. The increase correlated well with our previous finding of a four-fold increase in serum 3,5,3'-triiodothyronine concentration in cold-acclimated hamsters and the slow decline in concentration of this hormone during deacclimation. Daily administration of T3 (for 7 days) to warm-acclimated hamsters at 24 degrees C resulted in a similar increase in oxygen consumption that persisted 1 day after the last injection and had disappeared by 7 days after the last injection. We conclude that the high concentration of serum triiodothyronine in the cold-acclimated hamster exerts a thermogenic effect that probably contributes to thermoregulatory thermogenesis in the cold.     

Ketone bodies in cold-acclimated rats

Acclimation temperature (28 or 5 degrees C) modifies acetoacetate (AA) and beta-hydroxybutyrate (BOH) levels in blood and liver. In the fed state AA and BOH levels were increased in blood and liver of 5 degrees C adapted rats. In the fasting state (24 or 48 hr) an antiketotic action of cold acclimation was observed. It was found to be more pronounced with high fat diet. These effects were more marked in the blood than in the liver. The variations in ketonemia are discussed with relation to the role of liver in cold adapted rats.     

Non-shivering thermogenesis in winter-acclimatized and in long-scotophase and cold-acclimated Apodemus mystacinus (Rodentia)

1. 1.|Resistance to cold through non-shivering thermogenesis (the absolute increase in O₂ consumption caused by noradrenaline injection) was increased 3-fold in individuals of the broad-toothed mouse A. mystacinus, kept for 3 weeks under a short photoperiod (long scotophase 8L:16D) at an ambient temperature of 28°C, compared to control conditions (12L:12D; 28°C), and did not differ significantly from the winter-acclimatized group.

2. 2.|Acclimation of the same individuals to long scotophase and cold (8L:16d; 7°C) caused a significant (P < 0.01) increase in absolute O₂ consumption and maximal body temperature, as a response to noradrenaline injectin, when compared to long-scotophase individuals (8L:16D; 28°C).

3. 3.|The results of this study support the idea that winter acclimatization of heat-production mechanisims may be induced by the extension of scotophase, which cycles very regulary in nature and in the Mediterranean region occurs before the beginning of the cold season.

UCP1-independent thermogenesis in white adipose tissue of cold-acclimated Ucp1-/- mice

Apart from UCP1-based nonshivering thermogenesis in brown adipocytes, the identity of thermogenic mechanisms that can be activated to reduce a positive energy balance is largely unknown. To identify potentially useful mechanisms, we have analyzed physiological and molecular mechanisms that enable mice, genetically deficient in UCP1 and sensitive to acute exposure to the cold at 4 degrees C, to adapt to long term exposure at 4 degrees C. UCP1-deficient mice that can adapt to the cold have increased oxygen consumption and show increased oxidation of both fat and glucose as indicated from serum metabolite levels and liver glycogen content. Enhanced energy metabolism in inguinal fat was also indicated by increased oxygen consumption and fat oxidation in tissue suspensions and increased AMP kinase activity in dissected tissues. Analysis of gene expression in skeletal muscle showed surprisingly little change between cold-adapted Ucp1+/+ and Ucp1-/- mice, whereas in inguinal fat a robust induction occurred for type 2 deiodinase, sarcoendoplasmic reticulum Ca2+-ATPase, mitochondrial glycerol 3-phosphate dehydrogenase, PGC1alpha, CoxII, and mitochondrial DNA content. Western blot analysis showed an induction of total phospholamban and its phosphorylated form in inguinal fat and other white fat depots, but no induction was apparent in muscle. We conclude that alternative thermogenic mechanisms, based in part upon the enhanced capacity for ion and substrate cycling associated with brown adipocytes in white fat depots, are induced in UCP1-deficient mice by gradual cold adaptation.