Role of endocrine pancreas in temperature acclimation

Role of endocrine pancreas in temperature acclimation in rats was investigated. Plasma glucagon level increased and insulin level decreased in cold-acclimated rats (CA). The reverse was observed in heat-acclimated rats (HA). In the pancreas there were no changes in glucagon and insulin in CA, but a decrease in glucagon and an increase in insulin were found in HA. Plasma insulin/glucagon molar ratio (I/G) declined in CA and rose in HA. Pancreatic I/G rose in HA. Acute cold exposure elevated plasma glucagon, but did not affect plasma insulin. Pancreatic glucagon, insulin and I/G were not influenced by acute cold exposure, while plasma I/G decreased. Plasma I/G was inversely correlated with both blood free fatty acids and glucose levels. These results suggest that endocrine pancreas is closely associated with metabolic acclimation to cold and heat through its regulation of the metabolic direction to catabolic phase in cold acclimation and to anabolic phase in heat acclimation.     

Improved cold tolerance in glucagon-treated rats

In glucagon-treated rats (50 μg/100g, twice a day, 4 wks, sc) (GTR), the weights of liver and interscapular brown adipose tissue (BAT), and the level of plasma glucagon increased as compared with those in the vehicle-treated controls (VC). Mitochondria of BAT were markedly developed in size and cristae. Cold tolerance as assessed by the rate of fall in colonic temperature at ?5 °C was improved. Elevations of colonic temperatures by noradrenaline (40 μg/100g, im) were significantly enhanced in GTR. After cold exposure, blood free fatty acids (FFA) and plasma glucagon levels increased, but blood glucose and β-hydroxybutyrate levels were not changed in VC. Both blood FFA and β-hydroxybutyrate levels increased and blood glucose level decreased, but plasma glucagon levels was not affected by cold exposure in GTR. These results suggest that glucagon is involved in cold acclimation by means of enhanced nonshivering thermogenesis, possibly due to an activation of BAT as well as increased production and utilization of ketone bodies in the liver.     

Changes in thyroid hormone and insulin status of the brown adipose tissue of cold acclimated rats on short term exposure to heat

Acclimation of rats to cold caused 45% increase in the concentration of triidothyronine (T3) and 35% increase in the concentration of thyroxine (T4) in serum. Exposure of cold-acclimated rats to heat (12 hr, 37 degrees C) failed to decrease the concentrations of thyroid hormones in circulation. The concentration of T3 in brown adipose tissue (BAT) increased almost 10-fold on cold acclimation. Iodothyronine deiodinase activity also registered 3-fold increase. Exposure of cold-acclimated animals to heat caused decrease in the concentration of T3 in BAT without appreciably affecting T4 concentration. In liver tissue, the changes in hormone concentrations were quite small compared to those in BAT. On thyroidectomy or when fed with propyl thiouracil, rats could not survive exposure to the cold. The concentration of insulin in circulation showed small increase, while that in the tissues showed significant decrease on acclimation of rats to the cold. The concentration of the hormone in BAT registered significant increase on exposure of cold-acclimated animals to heat (12 hr, 37 degrees C). The increase in liver was marginal. The temperature-dependent response of T3 indicates an important role for this hormone in rapid physiological response in BAT.     

Modified metabolic responsiveness to glucagon in cold-acclimated and heat-acclimated rats

Calorigenic effect of glucagon on whole body oxygen consumption and interscapular brown adipose tissue (BAT) was investigated in unanesthetized and unrestrained warm controls (WC), cold-acclimated rats (CA) and heat-acclimated rats (HA). Glucagon produced significant elevation of oxygen consumption, body temperature and BAT temperature in all experimental groups. Such increased calorigenic responses to glucagon were significantly potentiated in CA and reduced in HA compared with those in WC. Thermogenic response of BAT to norepinephrine was also similar to that to glucagon; it was potentiated in CA, reduced in HA. These results indicate that glucagon would serve thermoregulatory nonshivering thermogenesis in temperature acclimation as calorigenic hormone, at least in part, through its action on BAT.     

Increased respiration in skeletal muscle mitochondria from cold-acclimated ducklings: uncoupling effects of free fatty acids

Intermyofibrillar mitochondria from skeletal muscle (m. gastrocnemius) and liver mitochondria were isolated from cold-acclimated (4 degrees C) or control (30 degrees C) 4-week old ducklings. The respiratory rate of isolated mitochondria, with Na-succinate as substrate, was followed polarographically at 25 degrees C in order to determine the basal respiratory rate, the rate of respiration in the presence of free fatty acids (FFA) (Na-palmitate), and the fully uncoupled rate, after addition of FCCP. The basal respiration (which in liver mitochondria was unaffected by acclimation to cold) was higher (+53%) in intermyofibrillar mitochondria from cold-acclimated ducklings than from controls, and the maximal FCCP-stimulated respiration was also increased (+98%) by acclimation to cold. FFA-stimulated respiration increased as a function of FFA concentration in both types of mitochondria. The increase in respiration due to FFA was about double in intermyofibrillar mitochondria from cold-acclimated ducklings than that of controls, but in liver mitochondria there was no increase due to cold. The membrane potential was estimated by the dye safranine in the absence or in the presence of FFA in the incubation medium. There were no significant differences in the basal membrane potential in the two groups and the addition of FFA led to the same depolarization in both groups. The significance of these alterations for acclimation to cold is discussed.     

Heat acclimation causes some alterations in serum enzymes activities in streptozotocin-diabetic rats

The present study investigated the effect of long-term heat acclimation and experimental diabetes on serum activity of transaminases (AST, ALT), ALP, LDH and elastase complex, as well as blood glucose and HbA1c level in Wistar rats. The heat acclimation model was established with the artificial heat chamber (35±1 °C and 30-40% humidity) for a period of 28 days, while the control groups were held on 20±2 °C. Experimental diabetes was induced by single streptozotocine (STZ) injection (55 mg/kg bodyweight) The changes caused by insulin treatment (2 IU/100 g body weight, 14 days, twice daily) in both thermal groups were also investigated.STZ-diabetes leads to significant increase in blood glucose and HbA1c level, AST, ALT and ALP activities in both thermal groups (normothermic and heat acclimated), decrease in LDH activity in normothermic animals and increase in heat-acclimated ones. Treatment with insulin restores the blood glucose, HbA1c and enzymes activities regardless of the previous thermal exposure.Prolonged acclimation of control animals to elevated ambient temperature resulted in significant decrease in blood glucose level, AST, ALT, ALP and LDH activities and non-significant changes in HbA1c. Compared to diabetic rats from room temperature, heat-acclimated diabetic ones have significantly higher blood glucose, AST, ALP and LDH activity, lower HbA1c concentration and no significant changes in ALT. Most of the changes observed in heat-acclimated insulin-treated diabetic rats did not significantly differ compared to those from room temperature.The overall two-way ANOVA analyses showed that diabetic state causes significant changes in the blood glucose, HbA1c, AST, ALT and ALP activity, while heat acclimation causes significant changes only in HbA1c level and AST activity. Both of the factors (diabetic state and heat acclimation) have significant common effects on AST, ALP and LDH activity.     

温度逆境交叉适应对葡萄叶片膜脂过氧化和细胞钙分布的影响

 研究了高温锻炼对低温胁迫下和低温锻炼对高温胁迫下葡萄(Vitis vinifera)叶片中丙二醛（MDA）、谷胱甘肽(GSH)和抗坏血酸(AsA)含量变化以及细胞中Ca2+分布的影响。结果表明: 高（低）温胁迫使正常生长的叶片丙二醛含量升高, GSH和AsA含量下降,低（高）温锻炼预处理能减少MDA含量,提高GSH和AsA含量,抑制了由于温度胁迫引起MDA含量升高和GSH和AsA下降趋势。常温下葡萄叶肉细胞的Ca2+主要分布于液泡、细胞间隙中;高温胁迫和低温胁迫后,细胞质中聚集大量Ca2+沉淀颗粒,液泡中和细胞间隙Ca2+沉淀颗粒减少,叶绿体超微结构被破坏,Ca2+稳态平衡遭到破坏。高温锻炼后细胞质出现大量的Ca2+沉淀颗粒,主要来源于细胞间隙,低温锻炼后细胞质也出现大量的Ca2+沉淀颗粒,主要来源于液泡,两者的叶绿体超微结构都完整;高温锻炼的叶片经过低温胁迫和低温锻炼的叶片经过高温胁迫后,细胞间隙和液泡内Ca2+沉淀颗粒增加,细胞质中Ca2+沉淀颗粒很少,叶绿体较完整,Ca2+稳态平衡得以维持。推测高低温锻炼能够通过Ca2+启动抗逆基因表达和维持细胞中Ca2+稳态平衡来交叉适应低高温的胁迫。     

Effect of cold-acclimation on oxygen uptake and glucose production of perfused duckling liver

The control of hepatic metabolism by substrates and hormones was assessed in perfused liver from young Muscovy ducklings. Studies were performed in fed or 24-h fasted 5-week-old thermoneutral (25 degrees C; TN) or cold-acclimated ducklings (4 degrees C; CA) and results were compared with those obtained in rats. Basal oxygen uptake of perfused liver (LVO2) was higher after cold acclimation both in fed (+65%) and 24-h fasted (+29%) ducklings and in 24-h fasted rats (+34%). Lactate (2 mM), the main gluconeogenic substrate in birds, similarly increased LVO2 in both TN and CA ducklings and the effect was larger after fasting. Both glucagon and norepinephrine dose-dependently increased LVO2 in ducklings and rats, but cold acclimation did not improve liver response and liver sensitivity to norepinephrine in ducklings was even reduced in CA animals. Liver contribution to glucagon-induced thermogenesis in vivo was estimated to be 22% in TN and 12% in CA ducklings. Glucagon stimulated gluconeogenesis from lactate in duckling liver and the stimulation was 2.2-fold higher in CA than in TN fasted birds. These results indicate a stimulated hepatic oxidative metabolism in CA ducklings but hepatic glucagon-induced thermogenesis (as measured by LVO2) was not improved. A role of the liver is suggested in duckling metabolic acclimation to cold through an enhanced hepatic gluconeogenesis under glucagon control.     

Lipolysis in brown adipose tissue of cold- and heat-acclimated hamsters

Rates of release of free fatty acids (FFA) and glycerol to the incubation medium by brown adipose tissue (BAT) slices isolated from heat-acclimated (H), cold-acclimated (C), and control (N) hamsters in the absence or presence of epinephrine (E) were studied. Rates of FFA and glycerol release by tissue slices isolated from H and N animals were similar. In tissue slices isolated from C animals rate of release of FFA and glycerol was three times as high. Addition of E to the incubation medium (200 microgram/ml) had no effect on the rate of FFA and glycerol release of slices from C animals, but tripled the rates of slices from N, resulting in similar values for the two groups. In slices from H animals the rate of release was lower than in the other two groups, increasing only 1.5-fold. Pretreatment of N animals with triiodothyronine (T3; 0.8 microgram/100 g daily for 7 days) doubled the rates of FFA and glycerol release. Addition of E to the medium affected both pretreated and nontreated slices similarly. Two possible mechanisms by which temperature acclimation controls the lipolytic rate of BAT are suggested by 1) the concentration of specific enzymes and 2) cellular metabolites and hormones which activate existing systems. It seems that both operate in temperature-acclimated hamsters.     

Temperature acclimation in the Mongolian gerbil (Meriones unguiculatus): biochemical and organ weight changes.

1. Adult Mongolian gerbils (Meriones unguiculatus) were acclimated to 5 +/- 1, 24 +/- 1 and 34 +/- 1 degrees C for 6-8 weeks. 2. Body weights of temperature acclimated gerbils did not differ significantly from controls. Organ wt/body wt ratios of liver, kidney and heart increased in cold-acclimated and decreased in heat-acclimated gerbils. Adrenal wt/body wt ratio increased in the cold and was unchanged in the heat. Relative weights of brain, spleen, lungs, brown fat and ovaries + uterus did not change with temperature acclimation. 3. Cold acclimation produced significant increases in specific and total activity of brown fat alpha GPO and liver SO and AAO and in total activity of kidney SO; a significant decrease in liver mitochondrial ADP/O ratio with succinate as substrate; and no change in brown fat SO or liver alpha KGO. 4. Heat acclimation produced significant decreases in specific and total activity of liver and kidney SO, and in total activity of brown fat SO and alpha GPO, and liver AAO and alpha KGO. 5. The combined biochemical and organ wt changes seen in temperature-acclimated gerbils suggest that this species is capable of altering its metabolic thermogenic potential in response to a wide range of ambient temperatures.     

The effect of photoperiod on changes in plasma, glucose, cholesterol, and free fatty acids during cold acclimation in frogs

1. Many previous experiments on cold acclimation in frogs were carried out on animals maintained in total darkness. I tested the effect of photoperiod on changes in plasma FFA, glucose, and cholesterol during cold acclimation. 2. Hematocrit levels were lower whereas plasma FFA levels were higher in frogs kept in total darkness during cold acclimation. 3. Plasma glucose and plasma cholesterol levels were not affected by photoperiod during cold acclimation.     

Impact of temperature on the relationship between respiration and nitrogen concentration in roots: an analysis of scaling relationships, Q10 values and thermal acclimation ratios

* The impact of nitrogen (N) supply on the temperature response of root respiratory O(2) uptake (R) was assessed in several herbaceous species grown in solution culture. Warm-grown (25 : 20 degrees C, day:night) plants differing in root N concentration were shifted to 13 : 8 degrees C for 7 d to cold-acclimate. * Log-log plots of root R vs root N concentration both showed that R increased with increasing tissue N concentration, irrespective of the growth temperature. Although the regression slopes of the log-log plots did not differ between the warm-grown and cold-acclimated plants, cold-acclimated plants did exhibit a higher y-axis intercept than their warm-grown counterparts. This suggests that cold acclimation of root R is not entirely dependent on cold-induced increases in tissue N concentration and that scaling relationships (i.e. regression equations fitted to the log-log plots) between root R and N concentration are not fixed. * No systematic differences were found in the short-term Q(10) (proportional change in R per 10 degrees C change in temperature), or degree of cold acclimation (as measured by the proportional difference between warm- and cold-acclimated roots) among roots differing in root N concentration. The temperature response of root R is therefore insensitive to tissue N concentration. * The insensitivity of Q(10) values and acclimation to tissue N concentration raises the possibility that root R and its temperature sensitivity can be predicted for a range of N supply scenarios.     

Interaction between heat acclimation and exogenous insulin in brown adipose tissue of rats

Seventy-one male Wistar strain rats (7 weeks old) were kept at 5, 25, or 34° C, respectively, for 2 weeks with or without insulin administration. Insulin (Novo Lente MC) was given subcutaneously in a dose of 3.62 nmol/125 µl saline per 100 g body weight. An apparent effect of insulin treatment was noted only in heat-exposed rats, resulting in a remarkable gain in inter-scapular brown adipose tissue (BAT) mass of heat-acclimated, insulin-treated rats in terms of weight or weight per unit body weight. The BAT from heat-acclimated, insulin-treated rats had significantly higher levels of protein, DNA, RNA, and triglyceride than BAT from heat-acclimated, saline-treated rats. Therefore, it seems likely that the growth of BAT in heat-acclimated, insulin-treated rats was mostly due to the anabolic effects of insulin. The uncoupling protein mRNA was, however, present in BAT of heat-acclimated, insulin-treated rats at rather a depressed level, explaining a corresponding decrease in cold tolerance. On the other hand, the expression of insulin receptor mRNA was attenuated in BAT of rats from all the insulin-treated groups, possibly due to the down-regulation of insulin. Thus, there appeared to be some linkage among BAT, heat acclimation, and insulin.     

Heat loss responses in rats acclimated to heat loaded intermittently

The present study examined the heat loss response of heat-acclimated rats to direct body heating with an intraperitoneal heater or to indirect warming by elevating the ambient temperature (Ta). The heat acclimation of the rats was attained through exposure to Ta of 33 or 36 degrees C for 5 h daily during 15 consecutive days. Control rats were kept at Ta of 24 degrees C for the same acclimation period. Heat acclimation lowered the body core temperature at Ta of 24 degrees C, and the core temperature level was lowered as acclimation temperature increased. When heat was applied by direct body heating, the threshold hypothalamic temperature (Thy) for the tail skin vasodilation was also lower in heat-acclimated rats than in the control rats. However, the amount of increase in Thy from the resting level to the threshold was the same in all three groups. When heat was applied by indirect warming, threshold Thy was slightly higher in heat-acclimated than in control rats. The amount of increase in Thy from the resting level to the threshold was significantly greater in heat-acclimated rats. In addition, Ta and the skin temperature at the onset of skin vasodilation were significantly higher in heat-acclimated rats. The results indicate that heat-acclimated rats were less sensitive to the increase in skin temperature in terms of threshold Thy. The gain constant of nonevaporative heat loss response was assessed by plotting total thermal conductance against Thy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of the Ca2+ cycle in uncoupling of oxidative phosphorylation in liver mitochondria of cold-acclimated rats

Cold acclimation of Wistar rats for 2-4 weeks at about 3 degrees C resulted in an increased respiration rate and a reduced ADP/O ratio in liver mitochondria. With increasing duration of acclimation up to 10-12 weeks, these parameters returned to a normal level. The increase in the respiration rate and the decline of the mitochondrial ADP/O ratio were associated with a significant activation of the electroneutral release of Ca2+. When the animals were acclimated for 10-12 weeks the rate of Ca2+ release reduced to control values. The addition of 1 microM ruthenium red resulted in a decrease in the rates of mitochondrial respiration in control and cold-acclimated rats to approximately equal values and in a partial restoration of the ADP/O ratio in liver mitochondria of rats kept in the cold for 2-4 weeks. The respiratory activity of mitochondria isolated in the presence of 1 mM EGTA unaffected by ruthenium red.     

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.     

Free radical equilibrium in interscapular brown adipose tissue: relationship between metabolic profile and antioxidative defense

Interscapular brown adipose tissue (IBAT) hyperplasia involves a new metabolic and structural profile, resulting from acclimation of animals to a cold environment. Cold-induced changes of several antioxidative defense (AD) components in IBAT and their interrelationship with uncoupling protein 1 (UCP1), sympathetic innervation and apoptosis were studied using cold-acclimated adult rat males (4 +/- 1 degrees C, 45 days). Their age-matches were maintained at 22 +/- 1 degrees C serving as the controls. In cold-adapted rats, activities of CuZn- and Mn-superoxide dismutase (SOD) and apoptosis were reduced, while catalase (CAT), glutathione peroxidase (GSH-Px), glutathione S-transferase (GST) activities and glutathione (GSH) content were increased compared to the control. IBAT mass, protein content, plasma free fatty acid (FFA) concentration, sympathetic innervation and UCP1 level were significantly increased in cold-acclimated group compared to the corresponding control. These results suggest that decreased CuZn and MnSOD activities in IBAT represent an adaptive response due to UCP1-induced mitochondrial uncoupling. Additionally, intensive fatty acid oxidation led to an increased H(2)O(2) production which resulted in increased CAT, GSH-Px and GST activities and GSH level. Generally speaking, cold-induced changes of AD in the IBAT are closely connected with newly established metabolic profile in this tissue, thus making an important part of the entire tissue homeostasis including cell survival.     

Hormonal and metabolic response to physical exercise, fasting and cold exposure in the rat. Effects on ketogenesis in isolated hepatocytes

Four groups of rats were subjected to the following conditions: (1) 48 h fasting, (2) 48 h of 4 degrees C cold exposure, (3) 5 h treadmill running, (4) 48 h fasting with 4 degrees C cold exposure. The groups were compared to fed control rats in order to study hormonal and metabolic responses in blood and tissue samples. Isolated hepatocytes were used to evaluate the rate of ketogenesis. Decreases in liver glycogen and increases in blood free fatty acids (FFA) confirmed that glycogenolysis and lipolysis occur in these situations of metabolic stress. Increases in the glucagon/insulin plasma ratio were also noted. Plasma catecholamine levels were only enhanced after running and after cold exposure. Production of blood ketone bodies was stimulated more by running and by fasting than by cold exposure. The low ketone body production observed after cold exposure seems to be linked to increases liver glycogen levels and decreased FFA availability. Liver cells isolated after cold exposure exhibited higher ketogenesis than these isolated after running. This difference in ketogenic capacity could result both from the longer hormonal stimulation by high glucagon/insulin plasma ratios and from the metabolic state of the liver.     

Mangiferin decreases plasma free fatty acids through promoting its catabolism in liver by activation of AMPK

Mangiferin has been shown to have the effect of improving dyslipidemia. Plasma free fatty acids (FFA) are closely associated with blood lipid metabolism as well as many diseases including metabolic syndrome. This study is to investigate whether mangiferin has effects on FFA metabolism in hyperlipidemic rats. Wistar rats were fed a high-fat diet and administered mangiferin simultaneously for 6 weeks. Mangiferin (50, 100, 150 mg/kg BW) decreased dose-dependently FFA and triglycerides (TG) levels in plasma, and their accumulations in liver, but increased the β-hydroxybutyrate levels in both plasma and liver of hyperlipidemic rats. HepG2 cells were treated with oleic acid (OA, 0.2 mmol/L) to simulate the condition of high level of plasma FFA in vitro, and were treated with different concentrations of mangiferin simultaneously for 24 h. We found that mangiferin significantly increased FFA uptake, significantly decreased intracellular FFA and TG accumulations in HepG2 cells. Mangiferin significantly increased AMP-activated protein kinase (AMPK) phosphorylation and its downstream proteins involved in fatty acid translocase (CD36) and carnitine palmitoyltransferase 1 (CPT1), but significantly decreased acyl-CoA: diacylgycerol acyltransferase 2 (DGAT2) expression and acetyl-CoA carboxylase (ACC) activity by increasing its phosphorylation level in both in vivo and in vitro studies. Furthermore, these effects were reversed by Compound C, an AMPK inhibitor in HepG2 cells. For upstream of AMPK, mangiferin increased AMP/ATP ratio, but had no effect on LKB1 phosphorylation. In conclusion, mangiferin decreased plasma FFA levels through promoting FFA uptake and oxidation, inhibiting FFA and TG accumulations by regulating the key enzymes expression in liver through AMPK pathway. Therefore, mangiferin is a possible beneficial natural compound for metabolic syndrome by improving FFA metabolism.