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Biomedical subjects

A Kuroshima

Publications and source records attributed to A Kuroshima.

At least 19 recordsLinked to original sources

Postnatal changes in fatty acids composition of brown adipose tissue.

It has been demonstrated that thermogenic activity of brown adipose tissue (BAT) is higher during the early postnatal period, decreasing towards a low adult level. The present study examined postnatal changes in the lipid composition of BAT. BAT from pre-weaning rats at 4 and 14 days old showed the following differences in lipid composition compared to that from adults of 12 weeks old. (i) Relative weight of interscapular BAT to body weight was markedly greater. (ii) BAT-triglyceride (TG) level was lower, while BAT-phospholipid (PL)level was higher. (iii) In TG fatty acids (FA) polyunsaturated fatty acids (PU; mol%), arachidonate index (AI), unsaturation index (UI) and PU/saturated FA (SA) were higher; rare FA such as eicosadienoate, bishomo-gamma-linolenic acid and lignoceric acid in mol % were also higher. (iv) In PL-FA monounsaturated FA (MU) in mol % was lower; PU mol %, AI and UI were higher. These features in BAT of pre-weaning rats resembled those in the cold-acclimated adults, suggesting a close relationship of the PL-FA profile to high activity of BAT.

Adipose Tissue, Brown

Effects of running training on in vitro brown adipose tissue thermogenesis in rats.

Brown adipose tissue (BAT) is a major site of nonshivering thermogenesis (NST) during cold acclimation for most mammals. Repetitive nonthermal stress such as immobilization has been shown to enhance the capacity of NST as cold acclimation. In the present study, the effects of running training, another type of nonthermal stress, were investigated on in vitro thermogenesis and the cellularity of interscapular BAT in rats. The rats were subjected to treadmill running for 30 min daily at 30m/min under 8 degrees inclination for 4-5 weeks. In vitro thermogenesis was then measured in minced tissue blocks incubated in a Krebs-Ringer phosphate buffer containing glucose and albumin at 37 degrees C, using a Clark type oxygen electrode. The trained rats showed less body weight gain during the experiment. The weights of BAT and epididymal white adipose tissue were smaller in the trained rats. Noradrenaline- and glucagon-stimulated oxygen consumption were also significantly smaller in the trained rats. The tissue DNA level was greater in the trained rats, but the DNA content per tissue pad did not significantly differ. The results indicate that running training reduces BAT thermogenesis, possibly as an adaptation to conserve energy substrates for physical work.

Adipose Tissue, Brown

Effects of chronic administration of noradrenaline and glucagon on in vitro brown adipose tissue thermogenesis.

The in vitro brown adipose tissue (BAT) oxygen consumption stimulated by noradrenaline (NA) or glucagon (G) was significantly lower in chronically NA-treated rats and that of G-treated rats did not differ as compared with that of vehicle-treated control animals. In vitro thermogenic response of BAT in NA-treated rats was consistent with that induced by cold acclimation.

Acclimatization

Effect of immobilization stress on in vitro and in vivo thermogenesis of brown adipose tissue.

Repetitive intermittent stress such as immobilization has been shown to induce an improved cold tolerance through an enhanced capacity of nonshivering thermogenesis (NST), causing positive cross adaptation between nonthermal stress and cold. In the present study, effect of 3-h-daily immobilization stress for 4-5 weeks was investigated on in vitro and in vivo thermogenesis of interscapular brown adipose tissue (BAT). In vitro thermogenesis was measured in the minced tissue blocks incubated in Krebs-Ringer phosphate buffer with glucose and albumin at 37 degrees C, using a Clark-type oxygen electrode. The stressed rats showed less body weight gain during the experiment. The BAT weight, its protein and DNA contents were significantly greater in the stressed rats. Basal, noradrenaline- and glucagon-stimulated oxygen consumptions were significantly greater in the stressed rats. In vivo thermogenesis was assessed by the changes of temperatures in colon (Tcol), BAT (TBAT), and tail skin (Tsk) induced by noradrenaline or glucagon infusion in the anesthetized rats. Noradrenaline and glucagon increased the TBAT and the extent of increase was greater in the stressed rats. These results indicate that cross adaptation between nonthermal stress and cold may be mediated through an enhanced thermogenic activity of BAT.

Acclimatization

Effects of cold acclimation on cold-induced changes in lipid metabolism of rat brown adipose tissue.

Effects of acute cold exposure (0 degree C, 12 h) on lipid metabolism of the interscapular brown adipose tissue (BAT) were studied in warm controls (25 degrees C) (WC) and cold-acclimated rats (5 degrees C, 4 weeks) (CA). 1) We confirmed that cold acclimation brought about decreased BAT triglyceride (TG) level and increased BAT phospholipid (PL) level. The indexes of unsaturation, such as unsaturation index and polyunsaturated fatty acids/saturated fatty acids ratio, of bulky fatty acids (FA) (palmitic, stearic, oleic, and linoleic acids) decreased in TG, while those increased in PL. Rare FA (eicosadienoic acid, homo-gamma-linoleinic acid, lignoceric acid) level, which were about five times higher in PL than TG in WC, decreased in both TG and PL in CA. 2) Effect of acute cold exposure in WC: The level as well as the amount of TG in BAT was greatly reduced and the indexes of unsaturation in TG-FA increased. The most part of reduced TG (85%) was explained by the bulky FA. Rare FA explained only 1.1% of reduced TG. PL level in BAT did not change, but its amount decreased. The indexes of unsaturation increased in PL-FA. 3) Effect of acute cold exposure in CA: CA was placed in warm temperature of 25 degrees C before cold exposure. In contrast with the cold-reduced TG in WC, either the level or the total amount of TG in BAT did not change, but the indexes of unsaturation in TG-FA decreased. The level as well as the total amount of PL in BAT increased. The arachidonic index and arachidonate in PL-FA decreased, but the indexes of unsaturation did not change. These results indicate as a whole that acute cold exposure as well as cold acclimation influences BAT lipid metabolism in FA compositions as well as amount of TG and PL, suggesting that such changes are related to thermogenic activity of this tissue.

Acclimatization

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.

Animals

Effects of exercise stress and cold stress on glutathione and gamma-glutamyltransferase in rat liver.

Effects of acute and chronic stress (exercise and cold) on glutathione and gamma-glutamyltransferase (gamma GT) in the rat liver were investigated. Such stress, except for in the case of acute exercise, had no definite influence on the glutathione level. On the other hand, gamma GT activity in both the extramicrosomal and microsomal fractions varied substantially, suggesting that acute exercise increases the release ability of the microsomal membrane of the rat liver, and that swimming training and long-term cold exposure stabilize the membrane. Immunoreactive gamma GT, however, did not always correlate with the enzyme activity, especially in the extramicrosomal fraction. Cross-adaptation appeared to exist between swimming training and chronic cold exposure.

Animals

Changes in fasting-induced adrenocortical secretion of cold-acclimated rats.

Effect of cold acclimation on fasting-induced adrenocortical and metabolic responses was studied in rats. The animals were acclimated to cold by exposure to 5 degrees C for 4 weeks. The warm control animals were kept at 25 degrees C for the same period. Fasting for 48 h decreased the body weight to the same extent in warm controls (WC) and cold-acclimated rats (CA). Plasma free fatty acids concentration increased by fasting, but the degree of increase did not differ between WC and CA. Plasma glucose level decreased in WC, while it increased in CA by fasting. Plasma corticosterone level was significantly higher in CA than in WC. Fasting increased the level in both groups, and the extent of increase as assessed by 95% confidence interval was significantly greater in CA as compared with that in WC. The present results indicate that fasting-induced glucocorticoid secretion is potentiated by cold acclimation, suggesting a possible role of this hormone in some metabolic changes in fasting.

Acclimatization

Cold-induced and postnatal changes in brown adipose tissue ganglioside levels.

Effects of cold and postnatal development were studied on brown adipose tissue (BAT) ganglioside levels in rats. Interscapular BAT was defatted by cold acetone before ganglioside extraction. Gangliosides were determined using HPTLC. Major ganglioside in BAT was found to be GM3. BAT GM3 level per g of fresh tissue weight as well as fat-free dry matter significantly increased in cold-acclimated rats (CA) and in rats reared in cold for 27 generations. BAT GM3 level per g of fresh weight as well as fat-free dry matter was significantly higher in 4-day- and 14-day-old rats than that in adult animals (12 weeks old). It was also shown that the higher levels of BAT GM3 were associated with greater BAT weight relative to body weight. These results suggest that BAT ganglioside, especially GM3, is implicated in growth and/or function of BAT in terms of cold-induced and postnatal changes of this tissue.

Acclimatization

Increased ACTH response to corticotropin-releasing factor in cold-adapted rats in vivo.

We have recently reported that chronically repeated restraint stress results in improved cold tolerance in rats via an increased activity of nonshivering thermogenesis, a characteristic metabolic change observed during cold adaptation, suggesting the presence of cross-adaptation between cold and stress. It is well established that the hypothalamic-pituitary-adrenal (HPA) axis is activated in various stress responses. In the present study, therefore, we examined whether cold adaptation would alter the adrenocorticotropic hormone (ACTH)-releasing state in vivo using freely moving, conscious rats chronically implanted with intra-atrial cannulas. There was no difference in the basal levels of plasma ACTH between warm control and cold-adapted rats. On the other hand, the ACTH response to the intravenous administration of corticotropin-releasing factor (CRF; 2 micrograms/animal) was significantly elevated in cold-adapted rats. However, the injection of 10 micrograms of CRF, which was considered as a dose to elicit the maximal ACTH response, resulted in similar ACTH release patterns between the two groups. These changes in the responsiveness of ACTH secretion have been observed in rats chronically exposed to stressful conditions. The results demonstrated in the present study, therefore, provide further evidence for our hypothesis that there may exist cross-adaptation between cold and nonthermal stress.

Adaptation, Physiological

Metabolic cold acclimation after repetitive intermittent cold exposure in rat.

Repetitive intermittent cold exposure (5 degrees C, 6 h/day, 4 weeks) (ICE) resulted in the same cold adaptability as assessed by an enhanced cold tolerance (less drop of colonic temperature at -5 degrees C) and nonshivering thermogenesis (NST) (greater noradrenaline-induced heat production) as that elicited by continuous cold exposure (5 degrees C, 4 weeks) (CA) in rats. Although shorter intermittent (5 degrees C, 2 h/day, 4 weeks) (ICE-2 hr) as well as shorter continuous (5 degrees C, 1 week) (CA-1 wk) cold exposure effected an improved cold adaptability, the magnitude of cold tolerance and NST was smaller as compared with that in CA and ICE. The cold deacclimation process as reflected on the decreased NST did not differ between CA and ICE. Food intake was less in ICE than CA, while increase in body weight during the acclimation period was greater in the former. Increase in adrenal weight was greater in CA than ICE, but plasma corticosterone level did not differ among warm controls (WC), CA, and ICE in resting state (after 18-20 h at warm control temperature of 25 degrees C). Weights of interscapular and dorsocervical brown adipose tissue (BAT) increased to the same degree in CA and ICE. Plasma glucagon level in resting state did not differ among groups, while BAT glucagon levels significantly increased in CA and ICE, but they were higher in dorsocervical site than interscapular site in all acclimated states. Acute cold exposure (-5 degrees C, 15 min) caused increases in plasma corticosterone, glucagon levels, and in BAT glucagon levels in all acclimated groups. The extent of increase was significantly less for plasma glucagon in CA, while plasma corticosterone increased similarly in all groups. These results indicate that repetitive short-term cold exposure could elicit the same cold adaptability as that induced by continuous exposure, but requiring only one-fourth of the time of continuous cold exposure. Moreover, it is suggested that glucagon is involved in both CA and ICE, but the same extent of cold adaptability can be obtained in the less energy-requiring and less stressful state in ICE.

Acclimatization

Noradrenaline-induced changes in rat brown adipose tissue glucagon.

Brown adipose tissue (BAT) glucagon level was higher in cold-acclimated rats (CA) than in warm controls (WC). Noradrenaline (NA) injection increased BAT glucagon levels in both WC and CA with increases in plasma glucagon levels. The magnitude of increase was significantly greater in CA for plasma glucagon, while it did not differ for BAT between groups. However, BAT glucagon was kept at a higher level in CA after NA injection than in WC.

Acclimatization

Effects of exercise, cold, and immobilization stresses on gamma-glutamyltransferase activity in rat kidney.

Effects of acute and chronic stresses (exercise, cold, and immobilization) on gamma-glutamyltransferase (gamma GT) activity in the rat kidney were investigated. In the extramicrosomal fraction there were significant decreases in acute-exercised rats but significant increases in cold-adapted and immobilized rats. In the microsomal fraction, on the other hand, the gamma GT activity of acute-exercised rats increased definitely. The results suggest that different types of stresses have different effects on gamma GT activity in the rat kidney.

Animals

[Studies on regulation of the function of thermogenic tissue, brown adipose tissue (BAT) by means of tissue culture method].

In order to clarify the regulatory mechanism of BAT function, the effects of noradrenaline (NA) (6mM), insulin (I) (40nM), glucagon (G) (400nM) and nerve growth factor (NGF) (2-10nM), alone or in combination, were investigated directly in BAT from neonatal rats (ca. 3 days old), cultured in 10% fetal bovine serum-medium 199 in 95% air-5% CO2 gas phase at 33 degrees C for 1 to 2 weeks. I stimulated lipid accumulation and enlarged outgrown cell size, but mitochondria in the cells of tissue block were smaller and their cristae less distinct. I + G enlarged nucleus and cytoplasm, and suppressed the lipid accumulation induced by I, but mitochondria in the cells of tissue block were larger and their cristae became more prominent than those of I-added cells. G induced the similar changes to those by I + G. I + NA also induced the similar effects to those by I + G, but their mitochondria size did not differ from that of I-added cells. NGF caused the similar effects of those by G, inducing the development of mitochondria, rough endoplasmic reticulum and Golgi complex. These results suggest that multiple factors such as NA, I, G and NGF regulate differentiation and functional development of BAT.

Adipose Tissue

Effect of noradrenaline on plasma hormones and metabolites in cold-acclimated rats.

The effects of noradrenaline (NA) injection (40 micrograms/100 g, i.p.) on plasma glucagon, corticosterone (CS), deoxycorticosterone (DOCS), glucose, and free fatty acids (FFA) were investigated in cold-acclimated rats (CA) and warm controls (WC). The CA were transferred to warm control temperature ca. 18 h prior to NA or saline injection. The animals were decapitated and the trunk blood was collected 0, 10, 20, and 40 min after the injection. Plasma glucagon level increased significantly during the experimental period after NA, while saline did not influence its level. The magnitude of increase as assessed by 95% confidence interval was significantly greater in CA than in WC. Plasma CS and DOCS were significantly increased by saline injection, but NA caused greater elevations of these steroid-hormones. The magnitudes of increases were also greater in CA. In contrast to the hormonal responses, NA-induced increases of plasma glucose and FFA levels were smaller in CA than in WC. These results suggest that glucagon and glucocorticoids are released, at least partly, by NA, and these thermogenic factors act in synergism, enhancing nonshivering thermogenesis through an accelerated utilization of energy substrates such as glucose and FFA.

Acclimatization

Gangliosides and energy substrates in brown adipose tissue of cold-acclimated rat.

Effect of cold acclimation on gangliosides as well as triglyceride and glycogen in brown adipose tissue was studied in rats. Ganglioside GM3 level per unit fresh weight and per unit fat-free-dry-matter was significantly higher in cold-acclimated rats (CA) than in warm controls, while the tissue triglyceride and glycogen levels were lower in CA. GM3 may be involved in cold-induced proliferation and differentiation of brown adipose tissue.

Acclimatization

Stress- and cold-induced adrenocortical responses in repetitively immobilized or cold-acclimated rats.

To evaluate the role of adrenocortical hormones in stress- or cold-induced nonshivering thermogenesis, plasma corticosterone (CS) and deoxycorticosterone (DOCS) were measured with the aid of HPLC under various conditions. Repetitive immobilization stress (3 h/day, for 1 or 4 weeks) elevated the resting level (24 h after the last immobilization) of CS, but not DOCS. Acute stress (immobilization for 30 min) or cold exposure (-5 degrees C for 15 min) caused marked increases of CS and DOCS in both nonstressed naive controls and repetitively stressed rats. Four weeks, but not 1 week, of repetitive immobilization stress potentiated the responsiveness of CS to both acute stress and cold, and that of DOCS to acute stress, but not to cold. Cold acclimation (5 degrees C, 4 weeks) significantly elevated both corticosteroids but did not affect the resting levels (18 h after being transferred to 25 degrees C) or the responsiveness of both CS and DOCS to either acute stress or cold. These results suggest that repetitive immobilization stress, but not cold acclimation, could enhance nonshivering thermogenesis, at least in part, through an improvement in the responsiveness of adrenocortical hormone secretion to acute stress or cold.

Acclimatization