Effects Of Chronic Cold Exposure Research Articles

Cold Exposure Alleviates T2DM Through Plasma-Derived Extracellular Vesicles.

Anecdotal reports have praised the benefits of cold exposure, exemplified by activities like winter swimming and cold water immersion. Cold exposure has garnered acclaim for its potential to confer benefits and potentially alleviate diabetes. We posited that systemic cold temperature (CT, 4-8°C) likely influences the organism's blood components through ambient temperature, prompting our investigation into the effects of chronic cold exposure on type 2 diabetic (T2DM) mice and our initial exploration of how cold exposure mitigates the incidence of T2DM. The effects of CT (4-8°C) or room temperature (RT, 22-25°C) on T2DM mice were investigated. Mice blood and organ specimens were collected for fully automated biochemical testing, ELISA, HE staining, immunohistochemistry, and immunofluorescence. Glucose uptake was assessed using flow cytometry with 2-NBDG. Changes in potential signaling pathways such as protein kinase B (AKT), phosphorylated AKT (p-AKT), insulin receptor substrates 1 (IRS1), and phosphorylated IRS1 (p-IRS1) were evaluated by Western blot. CT or CT mice plasma-derived extracellular vesicles (CT-EVs) remarkably reduced blood glucose levels and improved insulin sensitivity in T2DM mice. This treatment enhanced glucose metabolism, systemic insulin sensitivity, and insulin secretion function while promoting glycogen accumulation in the liver and muscle. Additionally, CT-EVs treatment protected against the streptozocin (STZ)-induced destruction of islets in T2DM mice by inhibiting β-cell apoptosis. CT-EVs also shielded islets from destruction and increased the expression of p-IRS1 and p-AKT in adipocytes and hepatocytes. In vitro experiments further confirmed its pro-insulin sensitivity effect. Our data indicate that cold exposure may have a potentially beneficial effect on the development of T2DM, mainly through the anti-diabetic effect of plasma-derived EVs released during cold stimulation. This phenomenon could significantly contribute to understanding the lower prevalence of diabetes in colder regions.

Chronic cold environment regulates rheumatoid arthritis through modulation of gut microbiota-derived bile acids

The pathologies of many diseases are influenced by environmental temperature. As early as the classical Roman age, people believed that exposure to cold weather was bad for rheumatoid arthritis (RA). However, there is no direct evidence supporting this notion, and the molecular mechanisms of the effects of chronic cold exposure on RA remain unknown. Here, in a temperature-conditioned environment, we found that chronic cold exposure aggravates collagen-induced arthritis (CIA) by increasing ankle swelling, bone erosion, and cytokine levels in rats. Furthermore, in chronic cold-exposed CIA rats, gut microbiota dysbiosis was identified, including a decrease in the differential relative abundance of the families Lachnospiraceae and Ruminococcaceae. We also found that an antibiotic cocktail suppressed arthritis severity under cold conditions. Notably, the fecal microbiota transplantation (FMT) results showed that transplantation of cold-adapted microbiota partly recapitulated the microbiota signature in the respective donor rats and phenocopied the cold-induced effects on CIA rats. In addition, cold exposure disturbed bile acid profiles, in particular decreasing gut microbiota-derived taurohyodeoxycholic acid (THDCA) levels. The perturbation of bile acids was also associated with activation of the TGR5-cAMP-PKA axis and NLRP3 inflammasome. Oral THDCA supplementation mitigated the arthritis exacerbation induced by chronic cold exposure. Our findings identify an important role of aberrant gut microbiota-derived bile acids in cold exposure-related RA, highlighting potential opportunities to treat cold-related RA by manipulating the gut microbiota and/or supplementing with THDCA.

Effects of Chronic Cold Exposure on Proteomics of Lung Tissue in Mice

Background: Cold exposure can induce inflammation-related injury in lung tissue, but the exact mechanism is still unclear. Objective: The study aimed to clarify the proteomic characteristics of lung tissue under cold exposure. Methods: Forty mice were randomly equally divided into a control group and a model group. The model group was exposed to - 20°C for two weeks (4 hours per day), while the control group was maintained at 22 ± 2°C. H&E staining and ELISA were used to verify the injury of lung tissue. Furthermore, a quantitative analysis of the overall proteome in the lung of mice exposed to cold stress was conducted by using LC-MS/MS. 15 differentially expressed proteins were selected for PRM validation. Results: According to our results, cold exposure induced lung injury, and the expressions of 151 proteins were upregulated and those of 95 proteins were downregulated. Bioinformatics analysis showed that differentially expressed proteins were associated with tricarboxylic acid cycle, fat metabolism, glycolysis, and oxidative phosphorylation. The expression of gabra2, Klkb1, and complement- related proteins was significantly upregulated. The results of PRM validation were consistent with those of proteomics. Conclusion: We found changes in glycolysis, gabra2, Klkb1, and the complement system in the lung tissue of cold-stressed mice, which may play an important role in cold stress-induced lung injury.

Glucose supplementation improves intestinal amino acid transport and muscle amino acid pool in pigs during chronic cold exposure.

Mammals in northern regions chronically suffer from low temperatures during autumn-winter seasons. The aim of this study was to investigate the response of intestinal amino acid transport and the amino acid pool in muscle to chronic cold exposure via Min pig models (cold adaptation) and Yorkshire pig models (non-cold adaptation). Furthermore, this study explored the beneficial effects of glucose supplementation on small intestinal amino acid transport and amino acid pool in muscle of cold-exposed Yorkshire pigs. Min pigs (Exp. 1) and Yorkshire pigs (Exp. 2) were divided into a control group (17°C, n=6) and chronic cold exposure group (7°C, n=6), respectively. Twelve Yorkshire pigs (Exp. 3) were divided into a cold control group and cold glucose supplementation group (8°C). The results showed that chronic cold exposure inhibited peptide transporter protein 1 (PepT1) and excitatory amino acid transporter 3 (EAAT3) expression in ileal mucosa and cationic amino acid transporter-1 (CAT-1) in the jejunal mucosa of Yorkshire pigs (P<0.05). In contrast, CAT-1, PepT1 and EAAT3 expression was enhanced in the duodenal mucosa of Min pigs (P<0.05). Branched amino acids (BCAA) in the muscle of Yorkshire pigs were consumed by chronic cold exposure, accompanied by increased muscle RING-finger protein-1 (MuRF1) and muscle atrophy F-box (atrogin-1) expression (P<0.05). More importantly, reduced concentrations of dystrophin were detected in the muscle of Yorkshire pigs (P<0.05). However, glycine concentration in the muscle of Min pigs was raised (P<0.05). In the absence of interaction between chronic cold exposure and glucose supplementation, glucose supplementation improved CAT-1 expression in the jejunal mucosa and PepT1 expression in the ileal mucosa of cold-exposed Yorkshire pigs (P<0.05). It also improved BCAA and inhibited MuRF1 and atrogin-1 expression in muscle (P<0.05). Moreover, dystrophin concentration was improved by glucose supplementation (P<0.05). In summary, chronic cold exposure inhibits amino acid absorption in the small intestine, depletes BCAA and promotes protein degradation in muscle. Glucose supplementation ameliorates the negative effects of chronic cold exposure on amino acid transport and the amino acid pool in muscle.

Cold Stress Induced Liver Injury of Mice through Activated NLRP3/Caspase-1/GSDMD Pyroptosis Signaling Pathway.

The body needs to generate heat to ensure basic life activities when exposed to cold temperatures. The liver, as the largest glycogen storage organ in the body and main heat-producing organ at rest, may play a role in chronic cold exposure. Recent studies suggested that pyroptosis plays a crucial role in liver diseases. However, the role of pyroptosis in cold stress-induced liver injury is not clear. Hence, in this study, we attempted to investigate the effects of chronic cold exposure on liver function, apoptosis, oxidative stress and inflammation in mice by establishing a mouse model of chronic cold exposure, and to investigate whether pyroptosis pathways are involved in the process of chronic cold exposure. In vivo, our results show that inflammatory cell infiltration and other pathological changes in liver cells and the activity of liver enzyme evidently increased in the serum and liver of cold-exposed mice, suggesting cold stress may result in liver injury. Remarkably, increased expression of heat shock protein 70 (HSP70) and HSP90 proteins proved the cold stress model is successfully constructed. Then, elevated levels of apoptosis, inflammation, oxidative stress and pyroptosis related proteins and mRNAs, such as cysteinyl aspartate specific proteinase-3 (Caspase-3), inducible nitric oxide synthase (iNOS), nuclear factor erythroid2-related factor 2 (Nrf2) and gasdermins D (GSDMD), confirmed that cold exposure activated apoptosis, oxidative stress and pyroptosis, and released inflammation cytokines. Meanwhile, in vitro, we got similar results as in vivo. Further, adding an NLR family pyrin domain containing 3 (NLRP3) inhibitors found that suppression expression of NLRP3 results in the essential proteins of pyroptosis and antioxidant evidently reduced, and adding GSDMD inhibitor found that suppression expression of GSDMD accompanies with the level of Nrf2 and heme oxygenase-1 (HO-1) obviously reduced. In summary, these findings provide a new understanding of the underlying mechanisms of the cold stress response, which can inform the development of new strategies to combat the effects of hypothermia.

Cold Exposure Induces Intestinal Barrier Damage and Endoplasmic Reticulum Stress in the Colon via the SIRT1/Nrf2 Signaling Pathway.

Ambient air temperature is a key factor affecting human health. Long-term exposure to a cold environment can cause various diseases, while the impact on the intestine, the organ which has the largest contact area with the external environment, cannot be ignored. In this study, we investigated the effect of chronic cold exposure on the colon and its preliminary mechanism of action. Mice were exposed to 4°C for 3 hours a day for 10 days. We found that cold exposure damaged the morphology and structure of the colon, destroyed the tight junctions of the colonic epithelial tissue, and promoted inflammation of the colon. At the same time, cold exposure also activated the unfolded protein response (UPR) in the colon and promoted apoptosis in intestinal epithelial cells. Chronic cold exposure induced oxidative stress in vivo, but also significantly enhanced the response of the Nrf2 pathway that promotes an anti-oxidant effect. Furthermore, we demonstrated that chronic cold exposure promoted p65 acetylation to aggravate the inflammatory response by inhibiting SIRT1. Similar results were observed following SIRT1 knock-down by shRNA in Caco-2 cells treated with Thapsigargin (Tg). Knock-down of SIRT1 promoted nuclear localization of Nrf2, and increased the level of Nrf2 acetylation. Taken together, our study indicates that cold exposure may aggravate endoplasmic reticulum stress and damage epithelial tight junctions in the colon by inhibiting SIRT1, which promotes nuclear localization of Nrf2 and induces an anti-oxidant response to maintain intestinal homeostasis. These findings suggest that SIRT1 is a potential target for regulating intestinal health under cold exposure conditions.

Cold exposure aggravates pulmonary arterial hypertension through increased miR-146a-5p, miR-155-5p and cytokines TNF-α, IL-1β, and IL-6

BackgroundCold temperatures can aggravate pulmonary diseases and promote pulmonary arterial hypertension (PAH); however, the underlying mechanism has not been fully explored. AimTo explore the effect of chronic cold exposure on the production of inflammatory cytokines and microRNAs (miRNAs) in a monocrotaline (MCT)-induced PAH model. MethodsMale Sprague Dawley rats were divided into a Control (23.5 ± 2 °C), Cold (5.0 ± 1 °C for ten days), MCT (60 mg/kg body weight i.p.), and MCT + Cold (ten days of cold exposure after 3 weeks of MCT injection). Hemodynamic parameters, right ventricle (RV) hypertrophy, and pulmonary arterial medial wall thickness were determined. IL-1β, IL-6, and TNF-α levels were determined using western blotting. miR-21-5p and -3p, miR-146a-5p and -3p, and miR-155-5p and -3p and plasma extracellular vesicles (EVs) and mRNA expression of Cd68, Cd163, Bmpr2, Smad5, Tgfbr2, and Smad3 were determined using RT-qPCR. ResultsThe MCT + Cold group had aggravated RV hypertrophy hemodynamic parameters, and pulmonary arterial medial wall thickness. In lungs of the MCT + Cold, group the protein levels of TNF-α, IL-1β, and IL-6 were higher than those in the MCT group. The mRNA expression of Cd68 and Cd163 were higher in the MCT + Cold group. miR-146a-5p and miR-155-5p levels were higher in the plasma EVs and lungs of the MCT + Cold group. Cold exposure promoted a greater decrease in miR-21-5p, Bmpr2, Smad5, Tgfbr2, and Smad3 mRNA expression in lungs of the MCT + Cold group. ConclusionCold exposure aggravates MCT-induced PAH with an increase in inflammatory marker and miRNA levels in the plasma EVs and lungs.

Finger cold-induced vasodilation of older Korean female divers, haenyeo: effects of chronic cold exposure and aging.

The aim of the present study was to evaluate the local cold tolerance of older Korean female divers, haenyeo (N=22) in terms of cold acclimatization and ageing. As control groups, older non-diving females (N=25) and young females from a rural area (N=15) and an urban area (N=51) participated in this study. To evaluate local cold tolerance, finger cold-induced vasodilation (CIVD) during finger immersion of 4°C water was examined. As a result, older haenyeos showed greater minimum finger temperature and recovery finger temperature than older non-diving females (P<0.05), but similar responses in onset time, peak time, maximum finger temperature, frequency of CIVD, heart rate, blood pressure, and thermal and pain sensations as those of older non-diving females. Another novel finding was that young urban females showed more vulnerable responses to local cold in CIVD variables and subjective sensations when compared to older females, whereas young rural females had the most excellent cold tolerance in terms of maximum temperature and frequency of CIVD among the four groups (P<0.05). The present results imply that older haenyeos still retain cold acclimatized features on the periphery even though they changed their cotton diving suits to wet suits in the early 1980s. However, cardiovascular responses and subjective sensations to cold reflect aging effects. In addition, we suggest that young people who have been adapted to highly insulated clothing and indoor heating systems in winter should be distinguished from young people who were exposed to less modern conveniences when compared to the aged in terms of cold tolerance.

Effects of chronic cold exposure on murine central nervous system

Recently, cold-adaptation medicine has gotten more and more attention because of its specific significance to health care, military activities, sports performance, and so on. Although numerous studies have focused on respiratory, immune, and circulatory systems as well as skin damage upon cold exposure, the impacts on central nervous system are not well understood. This study explores the effects of chronic cold exposure on the murine central nervous system. To establish a chronic cold-exposure animal model, adult male mice from postnatal days 40-50 (P40-50) were housed at 0-4°C for 20 days. During the study period, estrogen receptors were labeled via immunohistochemistry, the dendritic spines of visual cortical pyramidal cells were labeled with DiI diolistic assay, and synaptic ultrastructure was observed by transmission electron microscopy. The results showed that cold exposure could inhibit neural proliferation significantly, with an increase of G-protein-coupled receptor 30 (GPR30) expression. Chronic cold exposure could also induce a decrease in the dendritic spines of pyramidal cells in visual cortex, along with a decrease in the number of synaptic formations. The ultrastructure of synapses after cold exposure was observed. It was found that pre- and postsynaptic membranes were fused, with a vague synaptic cleft. Furthermore, neuronal cytoplasmic and organelle swellings were also observed, along with microtubule disintegration. In conclusion, chronic cold exposure can cause structural and functional changes in the mouse central nervous system, possibly by direct participation of estrogen and its receptor, GPR30, in response to chronic cold exposure.

Influence of Chronic Exposure to Cold Environment on Thyroid Gland Function in Rabbits

Chronic exposure to cold can affect the thyroid gland. However, the effect on thyroid gland perfusion images and the ratio between thyroid hormones secretion were not addressed in any previous study. The present study investigates the effects of chronic cold exposure on thyroid gland function using radionuclide tracer and thyroid hormones secretion concentration. New Zealand white rabbits weighing approximately 1.8-2 kg were kept in a cold room (4°C) for 7 weeks. Thyroid scintigraphy was performed for cold exposed rabbits and a control rabbit group. Each rabbit was injected with 115 MBq (3.1 mCi) technetium-99m pertechnetate (99mTc pertechnetate). Studies were performed using Gamma camera equipped with a low energy, high resolution, pinhole collimator interfaced with a computer. Static images were acquired 20 min after administration of the radiotracer. Rabbits chronically exposed to cold had less body weights than control. Thyroid gland uptake is higher in rabbits chronically exposed to cold than controls using radionuclide perfusion study. The increase was proportional to the time period, so the increase after 7 weeks was greater than 5 weeks. There is also an increase in free triiodothyronine (FT3) and a decrease in free thyroxine (FT4) values. Our results indicate that thyroid gland uptake is higher in rabbits chronically exposed to cold than control and the increase was proportional to the duration. The decrease in rabbit body weights may be related to the increase in metabolism due to the increase of thyroid hormones. Chronic cold exposure also increased the conversion of T4 to T3, which is more potent in thermogenic effect.

Lung perfusion is affected by chronic cold exposure

Background/AimThe Respiratory system can be affected by exposure to cold. It is well known that acute cold exposure induces asthmatic attacks. However, the influence of chronic cold environment exposure on lung perfusion and the pulmonary circulation was not studied in any previous study. Therefore this study was designed to investigates the effects of chronic cold exposure on lung perfusion using radionuclide study. MethodsNew Zealand White rabbits were used in these experiments. The rabbits were kept in the cold room (4°C) for 7 weeks. Lung perfusion scintigraphy was performed at the end of this period. Each rabbit was injected with 74MBq (2mCi) technetium-99m macroaggregated of albumin (99mTc MAA). Perfusion studies were done using Gamma camera equipped with a low energy, high resolution, parallel hole collimator interfaced with a computer. Static images were obtained 5min after administration of the radiotracer. Static images were acquired include anterior/posterior (Ant/Post), right anterior oblique/left posterior oblique (RAO/LPO), right lateral/left lateral (RLat/LLat), right posterior oblique/left anterior oblique (RPO/LAO). ResultsRabbits chronically exposed to cold had lesser lung perfusion than controls using radionuclide perfusion study. The lung counts of chronic cold exposure (4°C) for 7 weeks on rabbit lung perfusion for 5min was 64±4%. (n=6, ⁎⁎⁎P<0.001). ConclusionsOur results indicate that chronic cold exposure decreased pulmonary circulation and lung perfusion in normal subjects. Therefore chronic cold exposure might worsen some diseases that are affected by cold such as asthma.

Effect of chronic cold exposure on noradrenergic modulation in the preoptic area of thermoregulation in freely moving rats

For this study, we compared the thermoregulatory involvement of noradrenaline (NA) in the medial preoptic area (mPOA) of non-cold acclimated rats to that of cold-acclimated rats. We quantified the release of NA in the mPOA during 3 h cold (5 °C) exposure in room-temperature-acclimated rats (RA group, kept at 23 °C for 2 weeks) and cold-acclimated rats (CA group, kept at 5 °C for 2 weeks). We concurrently monitored the core body temperature ( T c), heart rate (HR), and tail skin temperature ( T t). Cold exposure significantly increased T c and HR, and decreased T t in both groups. However, the cold-induced increase of the extracellular NA levels in mPOA was observed only in the RA group: not in the CA group. To elucidate these different results in NA levels further, and to evaluate participation of the mPOA in thermoregulation in the cold, we measured T c, HR, and T t during perfusion of α-adrenoceptor antagonist phenoxybenzamine during cold exposure (5 °C). This pharmacological procedure induced marked hypothermia, with decreases in HR only in the RA group; no changes were observed in T c or any thermoregulatory parameter in the CA group. These results suggest that NA in the mPOA modulates heat production in response to acute cold stress in the RA group. However, this thermoregulatory action of NA in the mPOA was attenuated in the CA group.

Effects of chronic cold exposure on the endothelin system

Cold temperatures have adverse effects on the human cardiovascular system. Endothelin (ET)-1 is a potent vasoconstrictor. We hypothesized that cold exposure increases ET-1 production and upregulates ET type A (ETA) receptors. The aim of this study was to determine the effect of cold exposure on regulation of the ET system. Four groups of rats (6-7 rats/group) were used: three groups were exposed to moderate cold (6.7 +/- 2 degrees C) for 1, 3, and 5 wk, respectively, and the remaining group was maintained at room temperature (25 degrees C) and served as control. Cold exposure significantly increased ET-1 levels in the heart, mesenteric arteries, renal cortex, and renal medulla. Cold exposure increased ETA receptor protein expression in the heart and renal cortex. ET type B (ETB) receptor expression, however, was decreased significantly in the heart and renal medulla of cold-exposed rats. Cold exposure significantly increased the ratio of ETA to ETB receptors in the heart. An additional four groups of rats (3 rats/group) were used to localize changes in ETA and ETB receptors at 1, 3, and 5 wk of cold exposure. Immunohistochemical analysis showed an increase in ETA, but a decrease in ETB, receptor immunoreactivity in cardiomyocytes of cold-exposed rats. Increased ETA receptor immunoreactivity was also found in vascular smooth muscle cells of cold-exposed rats. Cold exposure increased ETA receptor immunoreactivity in tubule epithelial cells in the renal cortex but decreased ETB receptor immunoreactivity in tubule epithelial cells in the renal medulla. Therefore, cold exposure increased ET-1 production, upregulated ETA receptors, and downregulated ETB receptors.

Chronic cold exposure affects the antioxidant defense system in various rat tissues

Background: Chronic exposure to stress alters the normal body homeostasis and, hence, leads to the development of various human pathologies, which might involve alterations in the antioxidant defense system. We studied the effect of chronic cold exposure on oxidative stress and antioxidant defense system in various rat tissues. Methods: Male albino rats (Wistar strain), 2–3 months old, were exposed to 3 weeks of cold treatment. Antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) were measured in addition to the antioxidants, ascorbic acid (AsA) and glutathione (GSH), and the prooxidants, lipid peroxides (LPO) and xanthine oxidase (XOD), in brain, heart, kidney, liver and small intestine using standard protocols. Results: Chronic cold exposure resulted in a significant increase in LPO in all the tissues studied while XOD was increased in the brain and intestine. Total SOD activity was significantly decreased in all the tissues, whereas CAT activity was significantly increased in the kidney and decreased in heart, liver and intestine in the animals exposed to cold. GPx activity was increased only in the brain and intestine of stressed rats. Chronic cold exposure resulted in significant decrease in GR activity in heart, liver and intestine. GST activity was increased (except heart) and GSH was significantly decreased in all the tissues in treated rats. AsA was increased in kidney and intestine but decreased in heart of stressed animals. Conclusions: The observed changes in the antioxidant defense system are tissue specific, but it is evident that chronic exposure to cold leads to oxidative stress by displacing the prooxidant–antioxidant balance of this defense system by increasing the prooxidants while depleting the antioxidant capacities.

Chronic exposure to cold stress alters electrophysiological properties of locus coeruleus neurons recorded in vitro.

Chronic stress exposure can alter central noradrenergic function. Previously, we reported that in chronically cold-exposed rats the release of norepinephrine and electrophysiological activation of locus coeruleus (LC) neurons is enhanced in response to multiple excitatory stimuli without alterations in basal activity. In the present studies, we used in vitro intracellular recording techniques to explore the effect of chronic cold exposure on the basal and evoked electrophysiological properties of LC neurons in horizontal slices of the rat brainstem. Consistent with our findings from in vivo experiments, chronic cold exposure did not affect basal firing rate. Furthermore, gross morphology of LC neurons and spike waveform characteristics were similar in slices from control and previously cold-exposed rats. However, excitability in response to intracellular current injection and input resistance were larger in slices from previously cold-exposed rats. In addition, the accommodation of spike firing in response to sustained current injection was smaller and the period of postactivation inhibition appeared to be less in LC neurons from cold-exposed rats. These data demonstrate that the stress-evoked sensitization of LC neurons observed in vivo is at least in part maintained in the slice preparation and suggest that alterations in electrophysiological properties of LC neurons contribute to the chronic stress-induced sensitization of central noradrenergic function observed in vivo. Furthermore, the present data suggest that an alteration in autoinhibitory control of LC activity is involved in the chronic stress-induced alterations. The enhanced functional capacity of LC neurons following cold exposure of rats may represent a unique model to study the mechanisms underlying the alterations in central noradrenergic function observed in humans afflicted with mood and anxiety disorders.

Effects of chronic cold exposure on the activities of cytochrome c oxidase, glutathione peroxidase and glutathione reductase in rat tissues ( Rattus norvegicus)

The effects of cold acclimation on the activity levels of cytochrome c oxidase, glutathione peroxidase and glutathione reductase in various tissues of the rat ( Rattus norvegicus) were investigated. One group was individually housed at 4±1°C and the other at 24±1°C for 6 months. Chronic cold acclimation resulted in significantly ( P<0.05) increased cytochrome c oxidase activity levels in liver, kidney, heart, interscapular brown adipose tissue and gastrocnemius muscle. The activity of glutathione peroxidase was significantly ( P<0.05) elevated in liver, interscapular brown adipose tissue, lung and muscle, whereas glutathione reductase was only significantly ( P<0.05) elevated in interscapular brown adipose tissue as a result of chronic cold exposure. The results obtained are possibly indicative of a positive compensatory response against the increased production of oxygen derived radicals as a result of chronic cold exposure.

Capillary geometry in the soleus muscle of rats cold-acclimatized for 68 generations.

The effects of chronic cold exposure on soleus muscle capillarity were examined, particularly in terms of the distribution of arteriolar and venular capillaries and their capillary domain area (CDA) in adult rats exposed to cold for 68 generations (CG; n = 6). These parameters were compared with those obtained from control rats (CON; n = 5) and deacclimatized rats (DCG; n = 4), reared in thermoneutral temperature after being reared for 11 generations in cold. Morphometric data were obtained from muscle cross sections exposed to a double-staining method that stained the arteriolar and venular portions of capillaries blue and red, respectively. In CG, the capillary densities of arteriolar and venular capillaries were significantly greater than that of both CON and DCG (P < 0.05). The CDA of arteriolar, intermediate and venular portions in CG was significantly smaller by 15, 14 and 13%, respectively, than those of respective portions in CON (P < 0.05). Although CDA of arteriolar and venular capillary portions was also smaller in DCG than in CON, the degree of reduction was less in DCG than in CG. The succinate dehydrogenase activity of soleus muscle was significantly greater in CG than in both CON and DCG (P < 0.05). These results suggest that adaptive changes in the oxygen transport system, identified as an increase in the number of arteriolar capillaries and a reduction in the diffusion distance for oxygen, were observed in the soleus muscle after chronic cold exposure. These changes may improve the effective oxygen supply to muscle tissues and enable muscle tissues to promote thermogenesis in the cold atmosphere.

Effect of chronic cold exposure on Na-dependent D-glucose transport along small intestine in ducklings.

In conditions of chronic cold exposure, ducklings develop a nonshivering thermogenesis that requires a high energy expenditure. Therefore, energy supply becomes essential to cold-acclimated ducklings, which increase their intake of carbohydrate-rich food. The aim of this work was to investigate the effect of cold acclimation on the activity of the intestinal brush-border Na(+)-D-glucose cotransport, which is the first major step controlling glucose entrance into an organism. Cotransport activity was determined by measuring D-glucose uptake in brush-border membrane vesicles isolated from different parts of the small intestine of thermoneutral control (25 degrees C) or cold-acclimated (4 degrees C) ducklings (Cairina moschata). Two D-glucose transport sites were described in ducklings: a high-affinity/low-capacity site and a low-affinity/high-capacity site. The former was mainly located in the ileum and the latter in the duodenum. These two transport sites were altered differently by cold exposure. Major alterations occur in the ileum where 1) a reduction in the Michaelis-Menten constant and maximal transport rate of the high-affinity site was observed, and 2) the occurrence of low-affinity site activity was noted in cold-acclimated ducklings, although it was not detected in the thermoneutral control group. Cold effect on the high-affinity site could be related to the changes in the ileal brush-border membrane vesicle lipids, whereas cold effect on the low-affinity site could be due, at least in part, to the higher glycosyl content found in this segment. The small intestine appears then able to react to cold exposure by increasing both its mucosa mass in proximal segments and D-glucose uptake capacity in ileum to respond to the higher energy demand induced by thermoregulatory requirements.

The effects of chronic cold exposure on diurnal corticosterone and aldosterone rhythms in Sprague-Dawley rats

Plasma corticosterone (CORT) and aldosterone (ALDO) exhibit diurnal rhythmicity. Cold exposure increases basal plasma CORT and ALDO levels. This study investigated the effects of cold exposure on CORT and ALDO diurnal rhythms. Twelve male Sprague-Dawley rats were housed at 23°C, adapted to a 12:12 day:night cycle (lights on 0900 h), and provided chow and water ad lib. On day 7, 100 μl tail blood samples were obtained every 4 h for 24 h beginning at 0900 h. The temperature of the animal room was lowered to 4°C. On days 7 and 14 of cold exposure, blood samples were obtained every 4 h as above. After 7 days at 4°C, CORT levels were elevated at 0900 h, 1300 h, and 0500 h ( p < 0.05) as compared to levels observed at 23°C. Peak CORT levels were observed at 2100 h in each 24-h sampling session with mean levels of 181.3 ± 23.3 ng/ml at 23°C, and 200.5 ± 16.4 ng/ml and 188.1 ± 19.9 ng/ml after 7 and 14 days at 4°C. In contrast, ALDO levels were elevated at all time points across the day:night cycle after 7 days at 4°C. After 14 days, ALDO levels were elevated at 0900 h, 1300 h, and 2100 h ( p < 0.05) as compared to levels observed at 23°C. Peak ALDO levels occurred at 2100 h in each 24-h sampling session with mean levels of 199.9 ± 24.4 pg/ml at 23°C, and 361.4 ± 18.2 pg/ml and 342.1 ± 31.6 pg/ml after 7 and 14 days at 4°C. Cold exposure initially elevated CORT and ALDO levels possibly by reducing the effectiveness of negative feedback of CORT on the hypothalamic-pituitary-adrenal axis. However, ALDO levels remained elevated after 14 days at 4°C while CORT levels returned to baseline, suggesting different regulatory mechanisms after prolonged cold exposure.

Effect of maternal cold exposure on brown adipose tissue and thermogenesis in the neonatal lamb.

1. This study examines the effect of chronic cold exposure during pregnancy, induced by winter shearing twin-bearing ewes 4 weeks before predicted lambing date, on O2 consumption and CO2 production during non-rapid-eye-movement (REM) sleep in lambs maintained for at least 1 h at warm (28-18 degrees C) and cold (14-5 degrees C) ambient temperatures at 1, 4, 14 and 30 days of age. This was combined with measurement of the thermogenic activity (GDP binding to uncoupling protein in mitochondrial preparations) of perirenal adipose tissue from lambs immediately after birth and at 33 days of age. 2. Lambs born from shorn (cold-exposed) ewes were 15% heavier (P < 0.01) and possessed 21% (P < 0.01) more perirenal adipose tissue that contained 40% more protein and mitochondrial protein than unshorn (P < 0.05) controls. Total GDP binding in perirenal adipose tissue was 40% greater (P < 0.05) in lambs born from shorn ewes but there was no difference in lipid content of this tissue between the two groups. 3. At 1 day of age, lambs born from shorn ewes exhibited a 16% higher (P < 0.05) rate of O2 consumption (per kilogram bodyweight) at the warm temperature and a 40% greater metabolic response to the cold ambient temperature. All lambs born from shorn ewes responded to cold exposure without shivering (i.e. via non-shivering thermogenesis) whilst shivering was measured in four out of seven lambs in the unshorn group. These differences had disappeared by 4 days of age as a result of a 25% increased (P < 0.01) rate of O2 consumption in the warm in lambs born from unshorn ewes and a 20% decrease (P < 0.05) in the response to the cold in lambs from shorn ewes. Shivering during cold exposure was measured in six out of nine lambs born from shorn ewes indicating a rapid alteration in thermoregulatory responses to cold during the first few days of life. 4. The levels of GDP binding and mitochondrial protein in perirenal adipose tissue fell by one-third in both groups of lambs during the first 33 days of life whereas lipid content either increased or was unchanged. This indicated that brown adipose tissue (BAT) was developing the characteristics of white adipose tissue.(ABSTRACT TRUNCATED AT 400 WORDS)