Akihiro Kuroshima

Involvement of nitric oxide in noradrenaline-induced increase in blood flow through brown adipose tissue

N omega-nitro-L-arginine methyl ester (L-NAME) (80 mg), a NO synthase blocker, completely abolished noradrenaline (NA)-induced increase in blood flow through brown adipose tissue (BAT) in the urethan-anesthetized rat. L-NAME suppressed NA-induced increase in blood flow dose-dependently. L-arginine (80 mg), but not D-arginine (80 mg), reversed the inhibitory effect of L-NAME (0.8 mg). NA-induced increase in BAT temperature was also decreased by L-NAME. These results suggest that nitric oxide mediates NA-induced increase in BAT blood flow.

Role of glucagon in metabolic acclimation to cold and heat

Abstract Plasma glucagon concentration increased in 2 weeks cold-acclimated rats, but it returned to normal value in 4 weeks cold-acclimated ones. Plasma free fatty acid (FFA) and β-hydroxybutyrate concentrations also showed the similar pattern of changes. Plasma glucagon and FFA concentrations decreased in both 2 weeks and 4 weeks heat-acclimated animals. Plasma β-hydroxybutyrate concentration was not changed by heat acclimation. Plasma glucose concentration decreased in heat-acclimated animals, while it was not affected by cold acclimation. There was a significant positive correlation between plasma glucagon and FFA levels as a whole in 2 weeks warm-, cold- and heat-acclimated rats, and in 4 weeks warm- and heat-acclimated ones. These findings would appear to indicate that in both cold and heat acclimation glucagon is closely involved as one member of a hormonal team through regulating lipid and carbohydrate metabolism.

Cross adaption between stress and cold in rats

Three-hour immobilization stress was imposed on male adult rats of Wistar strain by restraining them on a board 6 days a week for 1–8 weeks. The stressed rats showed less body weight gain during the experiment compared to the controls. These stressed animals manifested an improved cold tolerance as shown by no significant fall in colonic temperature in the cold at −5° C for 300 min during the experimental period, while the colonic temperature of the controls fell progressively. Nonshivering thermogenesis as assessed by noradrenaline-induced increase in oxygen consumption was significantly potentiated in the stressed rats. The weight and protein content of the intercapsular brown adipose tissue (BAT) increased and BAT mitochondria were more packed in the stressed rats. Plasma insulin, insulin/glucagon molar ratio and thyroxine levels were lowered in the stressed rats, while the plasma triiodothyronine level remained unchanged. Removal of interscapular BAT led to a loss of improved cold tolerance and a significant reduction of nonshivering thermogenesis in the stressed rats.These results indicate that repetitive stress may induce cross adaptation between stress and cold through an enhanced capacity of nonshivering thermogenesis mediated, at least in part, via stimulation of BAT function.

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.

Hormonal regulation of brown adipose tissue—with special reference to the participation of endocrine pancreas

Abstract 1. 1. The role of pancreatic hormones, especially glucagon in the thermogenic function of brown adipose tissue (BAT) was investigated in rats. 2. 2. Plasma glucagon level increased in the cold-acclimated rats, while it decreased in the heat-acclimated ones. A significant positive relationship was observed between plasma glucagon and blood free fatty acid (FFA) levels as a whole in the warm controls, cold-acclimated and heat-acclimated rats. 3. 3. Glucagon infusion provoked an immediate rise of blood FFA and glucose levels on the venous drainage from the interscapular BAT. The β-adrenergic blocker, propranolol, did not modify these lipolytic and glycogenolytic actions of glucagon. When glucagon infusion was prolonged, the elevation of blood FFA and blood glucose levels was markedly suppressed in the cold-acclimated rats. 4. 4. Glucagon exhibited a marked heat production in the isolated brown adipocytes. 5. 5. Chronic administration of glucagon caused an improved cold tolerance accompanied by enhanced activity of BAT and increased non-shivering thermogenesis. 6. 6.Cold acclimation markedly elevated the content of glucagon as well as insulin in the interscapular BAT, while heat acclimation decreased it. 7. 7.These results would appear to indicate that glucagon as well as insulin is closely involved in the metabolic temperature acclimation, possibly through activation or inhibition of thermogenic mechanism(s) residing in the BAT.

Improved cold tolerance in glucagon-treated rats

Abstract 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.

Calorigenic effects of noradrenaline and glucagon on white adipocytes in cold- and heat-acclimated rats.

Calorigenic actions of noradrenaline and glucagon on isolated epididymal fat cells from warmacclimated controls, cold-acclimated and heatacclimated rats were measured by the use of a twin-type conduction microcalorimeter. Both noradrenaline and glucagon stimulated heat production in isolated adipocytes maximally in doses of 1 μg/ml and 10μg/ml, respectively. Maximal responsiveness of adipocytes per unit cell to noradrenaline was not influenced by cold acclimation, while it was reduced by heat acclimation. Maximal response in total epididymal fat cells to noradrenaline was increased in cold acclimation and not changed in heat acclimation at increased numbers of adipocytes in both cold-acclimated and heatacclimated animals. Maximal response per unit cell as well as per total epididymal fat cells to glucagon was increased in cold acclimation and reduced in heat acclimation.The present results indicate that the modified responses of target adipocytes to noradrenaline and glucagon are involved in the development of temperature acclimation.

Effects of cold stress on glutathione and related enzymes in rat erythrocytes

Effects of acute and chronic cold stress on glutathione and related enzymes in rat erythrocytes were investigated. Blood from both cold-acclimated (CA) and cold-adapted (CG) rats had significantly lower concentrations of glutathione than blood from control animals. Superoxide dismutase activity was increased significantly in CA rats and tended to rise in CG rats. Activity of glutathione peroxidase in erythrocytes was inconsistent in that it tended to increase in CA rats but decreased significantly in CG rats. The results may imply that CG rats suffered deleterious effects of hydrogen peroxide. On the other hand, there were marked decreases in glutathione peroxidase and glutathione reductase activities in acutely cold-exposed rats in conjunction with unchanged levels of glutathione. In all treatments the state of riboflavin metabolism was estimated to be adequate, since no increases were observed in the erythrocyte glutathione reductase activity coefficient.

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 effect 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.

Economy of hormonal requirement for metabolic temperature acclimation

1. 1. Thermogenic responses to some hormones in termperature-acclimated rats were studied in order to evaluate the role of hormonal factors in temperature acclimation. 2. 2. Glucagon (100 μg 100 g−1, i.p.) produced significant elevation of whole-body O2 consumption (VO2), and intraperitoneal (IP) and interscapular brown adipose tissue (IBAT) temperatures in the unanaesthetized and unrestrained warm control rats (WC: 25°C, 4W), cold-acclimated ones (CA: 4°C, 4 W) and heat-acclimated ones (HA: 34°C, 4 W) for the period of 60 min. Such increased calorigenic responsiveness to glucagon was markedly potentiated in CA and reduced in HA as compared with that in WC. Glucagon-induced maximum increases in VstaggeredO2 and in IBAT temperature were positively correlated with IBAT weights, respectively. Similar results were also observed in the CA mice. 3. 3. Injection of triiodothyronine (T3; 50 or 100 μg 100 g−1, s.c.) caused and increase in VO2, and IP and IBAT temperatures in WC and CA for the period of 18–48 h. Calorigenic responsiveness to T3 was significantly potentiated in CA and suppressed in HA as compared with that in WC. 4. 4. Injection of Metopirone (20 mg 100 g−1, i.p.), which is known to cause compensatory increases of desoxycorticosteroids such as desoxycorticosterone or desoxycortisol, desoxycorticosterone and corticosterone (0.3 mg 100 g−1, s.c., respectively), produced greater increases in VO2 in CA than in WC. 5. 5. These findings suggest that thermogenic responsiveness to calorigenic hormones is modified by temperature acclimation, and that multiple hormonal factors contribute to the development and maintenance of regulatory NST during temperature acclimation.