Renal responses to chronic cold exposure

The aim of this study was to assess our hypothesis that the release of antidiuretic hormone (ADH), the renal concentrating response to ADH, or both is decreased by prolonged cold exposure. Six groups (n = 6/group) of rats were used. Three groups were exposed to cold (5 degrees C), whilethe remaining three groups were kept at room temperature (25 degrees C). It was found that urine osmolality decreased significantly and serum osmolality increased significantly during cold exposure. The ratio of water/food intake was not affected by prolonged cold exposure. However, prolonged cold exposure increased the ratio of urine output/food intake in the cold-exposed rats, indicating that more urine flow is required by the cold-exposed rats to excrete the osmotic substance at a given food intake. The difference between water intake and urine output decreased significantly in the cold-exposed rats. Thus, prolonged cold exposure increases water loss from excretion. Renal concentrating responses to 24-h dehydration and Pitressin were decreased significantly in the cold-exposed rats. Plasma ADH levels remained unchanged, but renal ADH receptor (V2 receptor) mRNA was decreased significantly in the cold-exposed rats. The results strongly support the conclusion that cold exposure increases excretive water loss, and this may be due to suppression of renal V2 receptors rather than inhibition of ADH release.     

高山姬鼠冷驯化过程中的能量收支

为探讨栖息于横断山地区高山姬鼠的能量代谢特征,采用食物平衡法,在冷驯化条件下,对其能量收支进行了测定。分别测定了冷驯化(5 ± 1℃ ,42 d)过程中,高山姬鼠体重、体温、每日摄入能、消化能、消化率、粪便能及可代谢能、可代谢率的变化。结果表明:随着冷驯化时间的延长,高山姬鼠的体重和体温降低,28 d 时达到最低值后保持稳定,其中体重在冷驯化14 d 时即与对照组有显著差异,28 d 时平均比对照组降低了15.5% ,体温在14 d 后和对照组有显著差异。每日摄入能、消化能、可代谢能升高,三者均在冷驯化14 d 后与对照组有极显著差异,21 d 时达到最高后保持稳定。粪便能、消化率和可代谢率在冷驯化过程中没有显著变化。高山姬鼠在冷暴露过程中,通过降低体重减少绝对能量需求;通过降低体温减少用于维持体温恒定所消耗的能量;通过增加能量摄入维持正常的生理机能。高山姬鼠在冷驯化过程中表现出的变化模式,与其低纬度、高海拔、年平均温度较低的生存环境有关,这在一定程度上反映了横断山区小型哺乳动物在低温胁迫下的生存机制和适应对策。     

Effect of intracerebroventricular angiotensin II on body weight and food intake in adult rats

We recently reported that intracerebroventricular infusions of ANG II decreased food intake and increased energy expenditure in young rats. The aim of the present study was to determine if intracerebroventricular ANG II has similar effects in adult rats. The time course of the effect was also investigated with the idea that at earlier time points, a potential role for increased hypothalamic expression of corticotropin-releasing hormone (CRH) in the anorexia could be established. Finally, the contribution of ANG II-induced water drinking to the decrease in food intake was directly investigated. Rats received intracerebroventricular saline or ANG II using osmotic minipumps. Food intake, water intake, and body weight were measured daily. Experiments were terminated 2, 5, or 11 days after the beginning of the infusions. ANG II (approximately 32 ng.kg(-1).min(-1)) produced a transient decrease in food intake that lasted for 4-5 days although body weight continued to be decreased for the entire experiment most likely due to increased energy expenditure as evidenced by increased uncoupling protein-1 mRNA expression in brown adipose tissue. At 11 and 5 days, the expression of CRH mRNA was decreased. At 2 days, CRH expression was not suppressed even though body weight was decreased. The decrease in food intake and body weight was identical whether or not rats were allowed to increase water consumption. These data suggest that in adult rats ANG II acts within the brain to affect food intake and energy expenditure in a manner that is not related to water intake.     

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.     

Regulatory alterations of daily energy expenditure induced by fasting or overfeeding in unrestrained rats

The consequences of fasting or overfeeding during 2 days on energy expenditure were investigated by continuously monitoring O2 consumption in unrestrained, unanesthetized rats. O2 consumption decreased by 15% on the 1st day of fasting and then by an additional 15% on the 2nd day. On the 3rd day, when rats were fed again, energy intake increased by 30% above control (prefasting) values, whereas energy expenditure rapidly increased but no more than control values. On the other hand, when ad libitum fed animals were offered a sucrose solution (32%) for 2 days, energy intake increased by 30% and energy expenditure by 9-12%. On the 3rd day, when the rats were fed with their normal diet, energy intake significantly decreased under control (preoverfeeding) values during one day, but energy expenditure rapidly returned to normal values. The results show that fasting decreases, whereas hyperphagia increases 24-h energy expenditure during the treatments. When the treatments are terminated, energy expenditure rapidly returns to normal values, but fasting induces a postfasting increase of energy intake (during 2 days), whereas hyperphagia, on the contrary, results in a transient decrease of appetite. This indicates that alterations of food intake induce compensatory changes of energy expenditure during the treatments, but that after the treatments, energy balance is normalized via regulatory adjustments in the ratio of energy expenditure over energy intake.     

Reversibility of cold-induced hypertension after removal of rats from cold

Chronic exposure of rats to cold air induces hypertension, including elevation of blood pressure and cardiac hypertrophy. The present study was designed to assess reversibility of these changes after removal from cold. Five groups of six male rats each were exposed to cold (5 +/- 2 degrees C) for 39 days, while six control rats were maintained at 26 +/- 2 degrees C. Systolic blood pressures of the rats in one of the cold-treated groups, as well as the controls, were measured twice weekly throughout the experiment. Blood pressure of the cold-exposed rats (150 +/- 3 mmHg; 1 mmHg = 133.3 Pa) became elevated significantly above that of controls (129 +/- 3 mmHg) within 4 weeks. On day 39 of cold exposure, one group (six rats) of the cold-treated rats was sacrificed while still in the cold. The remaining four groups of cold-treated rats were than removed from cold and kept at 26 +/- 2 degrees C. One group of cold-treated rats was sacrificed weekly thereafter. During the last week, the six control rats were also sacrificed. At death, the heart, kidneys, and adrenal glands were removed and weighed. Mean heart weight of the cold-treated group (346 +/- 7 mg/100 g body weight), sacrificed prior to removal from cold, was significantly (p less than 0.01) greater than that of controls (268 +/- 5 mg/100 g body weight). The increased heart weight of the cold-treated group appeared to result mainly from an increase in left ventricular weight.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of food restriction on cold adaptability of rats

To determine the role of the nutritional state in nonshivering thermogenesis during cold adaptation, cold adaptability was compared between cold-adapted (5 degrees C for 4-5 weeks) rats fed ad libitum and cold-adapted rats pair fed with warm controls having the same food intake. Cold-adapted pair-fed rats suffered a significant loss in body weight during cold exposure. However, brown adipose tissue (BAT) in both cold-adapted ad libitum fed and cold-adapted pair-fed rats was enlarged to the same extent as compared with that in control rats. Fat-free dry matter in BAT also increased in cold-adapted ad libitum fed and cold-adapted pair-fed rats to the same extent. Cold tolerance as assessed by the change in the colonic temperature at -5 degrees C was improved relative to control rats and was the same for cold-adapted ad libitum fed and cold-adapted pair-fed rats. Nonshivering thermogenesis as estimated by the noradrenaline-induced increase in oxygen consumption was significantly greater in the cold-exposed rats and there was no significant difference between cold-adapted ad libitum fed and cold-adapted pair-fed rats. These results suggest that an improved cold tolerance by means of nonshivering thermogenesis in brown adipose tissue is closely related to the low temperature itself but not the increased food intake which occurred in the cold.     

Role of the sympathetic nervous system in cold-induced hypertension in rats

Hypertension develops in rats exposed chronically to cold [6 +/- 2 degrees C (SE)] and includes both an elevation of mean arterial pressure and cardiac hypertrophy. Previous studies suggest that cold-exposed animals, at least initially, have a large sustained increase in the activity of their sympathetic nervous system, suggesting a failure of the baroreceptor system to provide sufficient negative feedback to the central nervous system. The present study was designed to investigate whether alterations in the activity of the sympathetic nervous system, including the baroreceptor reflex, occur during exposure to cold and whether they contribute to cold-induced hypertension. Twenty male rats were prepared with indwelling catheters in the femoral artery and vein. Ten of the rats were exposed to cold (6 +/- 2 degrees C) chronically, while the remaining 10 were kept at 26 +/- 2 degrees C. Withdrawal of arterial blood samples (less than 5 ml/kg), measurement of direct arterial pressures, and measurement of baroreflex function were carried out at 0800 h at intervals throughout the experiment. Norepinephrine and epinephrine concentrations in plasma were also determined at intervals throughout the experiment. Systolic, diastolic, and mean blood pressures of cold-exposed rats were increased to levels significantly above those of controls. The sensitivity of the baroreflex (delta heart period/delta mean arterial pressure) was decreased in the cold-treated group. The concentration of norepinephrine in plasma increased after 24 h of exposure to cold and remained elevated throughout the experiment, whereas the concentration of epinephrine in plasma increased initially but returned to control levels after 19 days of exposure to cold.(ABSTRACT TRUNCATED AT 250 WORDS)     

Metabolic activity in isolated hepatocytes from cold exposed rats subjected to 24-hour fasting.

The aim of this work was to study the metabolic activity in isolated hepatocytes from control rats and rats exposed for 15 or 30 days to cold, all subjected to 24-h fasting. Hepatocyte oxygen consumption was used as an index of metabolic activity. The results show that 24-h fasting induces a decrease in energy expenditure at the level of the liver in cold-exposed rats but not in control animals.     

Perinatal Lead (Pb) Exposure Results in Sex-Specific Effects on Food Intake,Fat, Weight,and Insulin Response across the Murine Life-Course

Developmental lead (Pb) exposure has been associated with lower body weight in human infants and late onset obesity in mice. We determined the association of perinatal Pb exposure in mice with changes in obesity-related phenotypes into adulthood. Mice underwent exposure via maternal drinking water supplemented with 0 (control), 2.1 (low), 16 (medium), or 32 (high) ppm Pb-acetate two weeks prior to mating through lactation. Offspring were phenotyped at ages 3, 6, and 9 months for energy expenditure, spontaneous activity, food intake, body weight, body composition, and at age 10 months for glucose tolerance. Data analyses were stratified by sex and adjusted for litter effects. Exposed females and males exhibited increased energy expenditure as compared to controls (p<0.0001 for both). In females, horizontal activity differed significantly from controls (p = 0.02) over the life-course. Overall, food intake increased in exposed females and males (p<0.0008 and p<0.0001, respectively) with significant linear trends at 9 months in females (p = 0.01) and 6 months in males (p<0.01). Body weight was significantly increased in males at the medium and high exposures (p = 0.001 and p = 0.006). Total body fat differed among exposed females and males (p<0.0001 and p<0.0001, respectively). Insulin response was significantly increased in medium exposure males (p<0.05). Perinatal Pb exposure at blood lead levels between 4.1 µg/dL and 32 µg/dL is associated with increased food intake, body weight, total body fat, energy expenditure, activity, and insulin response in mice. Physiological effects of developmental Pb exposure persist and vary according to sex and age.     

Use of the doubly labeled water technique in humans during heavy sustained exercise

We measured energy expenditure with the doubly labeled water technique during heavy sustained exercise in the Tour de France, a bicycle race lasting more than 3 wk. Four subjects were observed for consecutive intervals of 7, 8, and 7 days. Each interval started with an oral isotope dose to reach an excess isotope level of 200 ppm 18O and 130 ppm 2H. The biological half-lives of the isotopes were between 2.25 and 3.80 days. Energy expenditure was compared with simultaneous measurements of energy intake, and body mass and body composition did not change significantly. The doubly labeled water technique gave higher values for energy expenditure than the food record technique. The discrepancy showed a systematic increment from the first to the third interval, being 12.9 +/- 7.9, 21.4 +/- 9.8, and 35.3 +/- 4.4% of the energy expenditure calculated from dietary intake, respectively. Possible explanations for the discrepancy are discussed. The subjects reached an average daily metabolic rate of 3.4-3.9 or 4.3-5.3 times basal metabolic rate based on the food record technique and the doubly labeled water technique, respectively. Thus, when measured with the same technique, the energetic ceiling for performance in humans is comparable with that of animals like birds.     

Effect of a reduction in sodium intake on cold-induced elevation of blood pressure in the rat.

Chronic exposure of rats to cold (5 degrees C) induces hypertension within 3 weeks. The objective of this study was to determine the effect of treatment with graded levels of dietary NaCl on the induction of hypertension during chronic exposure to cold. Four groups of male rats were used. The first, given a commercial sodium-deficient diet containing 0.30% NaCl, served as the warm-adapted control group. The second, third, and fourth groups were given the same diet containing 0.075%, 0.15%, and 0.30% NaCl, respectively. Because cold-exposed rats ingest approximately twice as much food as warm-adapted controls, this represented half, the same, and twice the amount of NaCl ingested by the control group. The latter three groups were placed in cold air (5 degrees C). All cold-treated groups had an elevation of systolic blood pressure that was proportional to the concentration of NaCl in the diet by the seventeenth week of exposure to cold. Cardiac hypertrophy occurred to the same extent in all cold-exposed groups and was thus unaffected by the NaCl content of the diet or by the extent of elevation of blood pressure. Hence, cardiac hypertrophy during chronic exposure to cold is supported by other factors, possibly by the increased concentration of either norepinephrine or triiodothyronine, or both, which occurs characteristically in rats under these conditions. The results of this experiment suggest that the amount of NaCl ingested daily plays a role in the cold-induced elevation of blood pressure observed in rats.     

Modified activity-stress paradigm in an animal model of the female athlete triad.

The exercising woman with nutritional deficits and related menstrual irregularities is at risk of compromising long-term bone health, i.e., the female athlete triad. There is no animal model of the female athlete triad. The purpose of this study was to examine long-term energy restriction in voluntary wheel-running female rats on estrous cycling, bone mineral content, and leptin levels. Twelve female Sprague-Dawley rats (age 34 days) were fed ad libitum and given access to running wheels during an initial 14-wk period, providing baseline and age-related data. Daily collection included dietary intake, body weight, estrous cycling, and voluntary running distance. At 4 mo, rats were randomized into two groups, six restrict-fed rats (70% of ad libitum intake) and six rats continuing as ad libitum-fed controls. Energy intake, energy expenditure, and energy availability (energy intake - energy expenditure) were calculated for each animal. Serum estradiol and leptin concentrations were measured by RIA. Femoral and tibial bone mineral density and bone mineral content (BMC) were determined by dual-energy X-ray absorptiometry. Restrict-fed rats exhibited a decrease in energy availability during Weight Loss and Anestrous phases (P = 0.002). Compared with controls after 12 wk, restrict-fed rats showed reduced concentrations of serum estradiol (P = 0.002) and leptin (P = 0.002), lower ovarian weight (P = 0.002), and decreased femoral (P = 0.041) and tibial (P = 0.05) BMC. Decreased energy availability resulted in anestrus and significant decreases in BMC, estrogen and leptin levels, and body weight. Finally, there is a critical level of energy availability to maintain estrous cycling.     

Effects of leptin and cholecystokinin in rats with a null mutation of the leptin receptor Lepr(fak)

The Koletsky ("corpulent) obese rat is homozygous for an autosomal recessive mutation of the leptin receptor (Lepr) that results in hyperphagia, obesity, and hyperlipidemia. Unlike the Lepr mutation that characterizes the fatty Zucker rat (Lepr(fa)), the Koletsky mutation (Lepr(fak)) is null. Because the Lepr(fak) mutation is null, exogenous leptin should have no effect on body weight or food intake in fa(k)/fa(k) rats. We confirmed that prediction: murine leptin, administered into the third ventricle for 5 consecutive days, did not affect daily food intake or body weight in fa(k)/fa(k) rats but produced dose-related inhibitions of food intake and body weight in +/+ and +/fa(k) rats. Although fa(k)/fa(k) rats did not respond to leptin, their response to CCK-8 (4 microg/kg ip) injected before 30-min test meals of 10% sucrose was not different from that of +/+ or +/fa(k) rats. These results demonstrate that the fa(k)/fa(k) rat is a good model in which to analyze the controls of food intake, energy expenditure, and energy storage in the absence of leptin effects.     

Barn Swallow Hirundo rustica parents work harder when foraging conditions are good

In altricial birds, the great effort involved in supplying food to nestlings can create trade‐offs in the allocation of resources between the current brood and parental self‐maintenance. In poor foraging conditions, parents have to adjust their energy expenditure in relation to the increased foraging costs. However, intra‐specific variation in parental energy expenditure has rarely been evaluated in the context of these trade‐offs. Here, we quantified the daily energy expenditure (DEE) of parent Barn Swallows Hirundo rustica during the nestling period in relation to foraging conditions while controlling for differences in brood size and nestling age. DEE varied substantially with environmental conditions, increasing by 10 kJ/day per 5 °C in ambient temperature, and by 11 kJ/day per hour in day length. Parent birds did not compensate for a poor aerial insect supply on cool days, but reduced their DEE. Parents only slightly buffered a negative energy balance during chick provisioning with stored body reserves. They did not sacrifice their own energy demands to keep up a high energy flow to the brood when foraging conditions were poor. Instead they worked harder when foraging conditions allowed a surplus intake, fully compensating for their additional efforts, and made maximum use of the rich food supply, allowing the brood to accrue body reserves to compensate for low food intake on cold days. This strategy of energy management may have evolved in the context of the adaptation to the aerial foraging mode and to the ephemeral nature of aerial food resources.     

The effect of cold-acclimation on energy strategies of Apodemus draco in Hengduan Mountain region

Environmental factors play an important role in the seasonal adaptation of body mass and thermogenesis in small mammals. The purpose of the present study was to test the hypothesis that ambient temperature triggers adjustments in body mass, body temperature, energy intake, digestible energy intake, metabolic energy intake, and the length and weight of the digestive tract, in Apodemus draco during 42 days of cold exposure. Body mass and body temperature of the cold-acclimated group decreased during the first 28 days and then stabilized at the lower levels. After 14 days of cold acclimation, the body mass of the cold-exposed group was significantly lower and the energy intake, digestible energy intake, and metabolic energy intake were significantly elevated relative to control animals. The differences were maximal after 21 days. The length and weight of the digestive tract (both wet and dry mass of the stomach, small intestine, large intestine, and cecum) changed significantly in response to decreasing temperature. During cold exposure, A. draco was able to maintain physiological functions and reduce its absolute energy demands by reducing the body mass, increasing energy intake, and adjusting the length of the digestive tract.     

Serum leptin, energy budget, and thermogenesis in striped hamsters exposed to consecutive decreases in ambient temperatures

Leptin has been found to be a direct participant in the regulation of both energy intake and energy expenditure in small mammals showing seasonal declines in body mass (M(b)) and fat mass, but its roles in an animal exhibiting seasonally increased thermogenesis and unchanged M(b) remain unclear. Serum leptin levels, energy budget, and thermogenesis were measured in striped hamsters exposed to consecutive decreases in ambient temperatures ranging from 23° to -23°C. Cold-exposed hamsters had significant increases in gross energy intake (GEI), the rate of basal metabolism, nonshivering thermogenesis, and activity of cytochrome c oxidase (COX) in brown adipose tissue (BAT), compared with control hamsters, indicating a cold-induced elevation of thermogenesis. Body mass and fat content were decreased in cold-exposed animals, and serum leptin levels were increased in hamsters exposed to temperatures of -8°C and below in inverse proportion to body fat content. Serum leptin levels were positively correlated with GEI and BAT COX activity in cold-exposed hamsters, but no such relationships were observed in control animals. These findings suggest that cold-exposed hamsters increase food consumption to meet the energy requirements for increased BAT thermogenesis. The increases in serum leptin levels are likely involved in increased thermogenesis in hamsters under cold stress. Cold-exposed hamsters may become leptin resistant, which is associated with impaired regulation of food intake. This new natural model of leptin resistance may also provide insight into the dynamic long-term control of energy homeostasis for animals that do not exhibit seasonal decline in M(b).     

Combined effects of oleoyl-estrone and a beta3-adrenergic agonist (CL316,243) on lipid stores of diet-induced overweight male Wistar rats

Oleoyl-estrone (OE) decreases appetite, induces adipose tissue wasting and resets the ponderostat setting, sparing glucose and protein. The beta3-adrenergic agonists increase energy expenditure and lipolysis. We studied the combination of both treatments to enhance fat mobilization. Overweight male rats received oral OE for 10 days; they were compared with controls and rats receiving a beta3-adrenergic agonist, CL316,243 (B3A); another group received both OE and B3A. Serum 3-hydroxybutyrate, NEFA, triacylglycerols and glucose showed only slight changes in all groups vs. controls; OE-treated rats showed lower cholesterol. OE decreased food intake and B3A increased energy expenditure. OE rats lost about 15%, B3A 24%, and those receiving both compounds lost 39% of their initial total body energy. In all cases, most of this energy imbalance was accounted for by the loss of body lipid. The combined treatment of OE and B3A reduced food intake, nevertheless maintaining a high energy expenditure. The combination of a beta3-adrenergic agonist with OE may help compensate the short-lived effects of the agonist and enhance the lipid mobilization action of OE. The eventual combination of both compounds should be explored as a way to obtain faster and more effective ways to treat obesity.     

Thermogenic drinking: mediation by osmoreceptor and angiotensin II pathways

Exposure of rats to air at 5 C for 1-12 days is accompanied by a relative dehydration in spite of the continued presence of water. Dehydration during exposure to cold was manifested by: 1) a reduction in the ratio of water/food ingested; 2) an increase in the ratio of urine excreted/water ingested; 3) an increased evaporative water loss; 4) an increased serum osmolality and chloride concentration; and 5) a striking thirst and ingestion of water after transfer from cold to air at 26 C. Drinking began within 15 min and lasted approximately 1 h. Thermogenic drinking persisted for at least 120 days of exposure to cold. It was not thwarted by preventing access to water for either 1 or 2 h after transfer to warm air, but either intragastric or intraperitoneal administration of a water load equal to 3% of body weight inhibited water intake after transfer. These characteristics of thermogenic drinking are similar to those observed after 24 h of dehydration at 26 C; they also suggest that the cold-exposed rat is dehydrated relative to controls. These results suggest that osmoreceptors may play a role in the induction of thermogenic drinking. However, angiotensin II receptors may also play a role. Thermogenic drinking was inhibited by a beta 2-adrenergic, but not a beta 1-adrenergic, antagonist as well as by captopril, an inhibitor of the conversion of angiotensin I to angiotensin II. Further, plasma renin activity increased fourfold within 15 min after removal from cold. This suggests that an additional component involved in thermogenic drinking is the angiotensin II receptor. The extent to which thermogenic drinking is mediated by each pathway is unknown and will require additional studies.