Implications of interscapular brown adipose tissue removal and sucrose overfeeding on the sympatho-adrenal activity and metabolic responses

1. The influence of sucrose overfeeding on the sympatho-adrenal (SA) and metabolic responses was studied in sham-operated (SHAM) rats and in those with interscapular brown adipose tissue (IBAT) removed. 2. Sucrose feeding significantly increased the SA activity, mobilized the free fatty acids (FFA), but did not change glucose homeostasis in sham-operated rats. 3. IBAT removal in control rats fed a stock diet modified the SA activity whereas the levels of both blood glucose and serum FFA were unchanged. 4. However, sucrose in rats void of IBAT potentiated the activity of sympathetic nervous system only and prevented the FFA rise, which is seen in sham-operated sucrose fed rats indicating that the enhanced level of serum FFA in these animals principally originated from the IBAT.     

Influence of fasting and dopamine on the tissue catecholamines diurnal variations

To define the role of catecholamines (CA) in the metabolic adaptation to fasting we examined the effect of exogenous dopamine(DA) on heat production(HP) and CA content in the interscapular brown adipose tissue(IBAT) and adrenals of control-fed and 2-day fasted rats in the morning(M) and in the evening(E). DA stimulates HP in fed rats in the M by 45% but the thermogenic effect of this CA is markedly higher in the E. However, DA had no thermogenic effect in fasted rats. The tissue CA in fed rats fluctuates diurnally: in the IBAT noradrenaline(NA) was much higher in the E while adrenaline(A) in adrenals was lower. DA in fed rats did not change the adrenal A but reduced NA content both in the adrenals and in the IBAT all over the day. Fasting depleted A from adrenals but increased NA content both in the M and in the E. Unlike the adrenals in the IBAT fasting did not affect NA content. In the adrenal gland of fasted rats DA significantly increased the A content to the equal degree during the day, while this CA had no effect on NA content of the IBAT.     

Effects of ovariectomy on indices of insulin resistance, hypertension, and cardiac energy metabolism in middle-aged spontaneously hypertensive rats (SHR).

Insulin resistance is a risk factor for coronary heart disease. The protection of young women from coronary events is sharply reduced with menopause. To assess the impact of menopause on glucose tolerance, insulin resistance, body weight gain, heart size, and cardiac energy metabolism, we studied 28-week-old female SHR and Wistar-Kyoto (WKY) rats, who were either ovariectomized (SHR(OVX) and WKY(OVX)) or sham-operated (SHR(SHAM) and WKY(SHAM)). Animals underwent blood-pressure measurement and an oral glucose tolerance test (OGTT). Hearts were weighed and assayed for metabolic enzyme activities. Female SHR were 33 % lighter and hypertensive (+ 36 mmHg), with 33 % larger hearts (when corrected for body weight differences) compared to WKY. Although ovariectomized animals of both strains were heavier overall than their sham-operated counterparts, when heart weights were corrected for body weight, both OVX strains had lighter hearts than both SHAM strains. Glucose and insulin responses during OGTT were similar between the four groups; however, free fatty acid (FFA) responses were approximately 50 % greater in SHR than WKY, although less in SHR(OVX) than SHR(SHAM). WKY(OVX) demonstrated 8 % lower ventricular hexokinase activity than WKY(SHAM), which may reflect reduced cardiac glucose utilization. We also noted 16 % higher citrate synthase activity in WKY hearts. In conclusion, the insulin resistance characteristic of younger SHR is blunted in middle-aged female rats, although FFA responses remain elevated. Ovariectomy did not alter in vivo glucose tolerance in this group; however, sex hormones may be important in maintaining normal heart size and the potential for cardiac glucose metabolism.     

Effect of fasting and refeeding on the activities of monoamine oxidase and antioxidant enzymes in rat hypothalamus and brown adipose tissue

Fasting for 48 h and the same period of recovery induced by 48 h refeeding increased rat hypothalamic monoamine oxidase (MAO) activity. However, in the interscapular brown adipose tissue (IBAT), only refeeding induced a significant elevation of the enzyme activity. As far as hypothalamic antioxidative enzymes are concerned, the copper zinc superoxide dismutase (CuZnSOD) activity was decreased in refed rats only. However, in the IBAT both food deprivation and refeeding induced a significant decrease in catalase (CAT) activity. Under the influence of fasting the adrenal glands were strongly activated as judged by the increased dopamine-beta-hydroxylase (DBH) activity and decreased cholesterol concentration. Refeeding brought both parameters to control levels indicating full recovery of these glands. As expected, fasting for 48 h induced a significant decrease in serum glucose but an increase in FFA concentrations. Thus, it can be concluded that both fasting and refeeding resulted in increased activation of hypothalamic MAO, whereas CuZnSOD activity was decreased only by refeeding. However, in the IBAT only refeeding increased MAO activity whereas both fasting and refeeding decreased that of CAT. In conclusion, it may be assumed that food deprivation for 48 h and the same duration of refeeding influenced MAO and antioxidative enzymes activities in the rat hypothalamus and IBAT in a tissue specific manner.     

Effects of nicotinic acid on fatty acid kinetics, fuel selection, and pathways of glucose production in women

Chronic nicotinic acid (NA) ingestion effectively lowers lipid levels, but adverse effects on glucose metabolism have been reported. Our goal was to investigate acute and chronic effects of NA on lipolysis and glucose metabolism in women. Healthy normolipidemic volunteers (n = 5) were studied twice; four-day hospital stays were separated by 1 mo, during which time subjects took increasing doses of NA to 2 g/day (500 mg, 4 times). In the second study, 500 mg of NA was given at 0800. Rates of appearance (R(a)) of free fatty acid (FFA), glycerol, and glucose were determined by isotope dilution (of [1,2,3,4-(13)C(4)]palmitate, [2-(13)C(1)]glycerol, and [U-(13)C(6)]glucose). Mass isotopomer distribution analysis was used to measure gluconeogenesis and glycogenolysis. Fasting FFA concentrations ([FFA]), R(a) FFA, and R(a) glycerol were nonsignificantly elevated after 1 mo. Acute NA induced a significant reduction followed by a rebound overshoot of [FFA], R(a) FFA, and R(a) glycerol. Whole body fat oxidation fell initially and then increased back to basal levels; endogenous glucose production (EGP) increased in parallel with carbohydrate oxidation and then returned to basal values. The increased EGP was due entirely to increased glycogenolysis, not gluconeogenesis. We conclude that chronic effects of NA on FFA metabolism are complex (acute suppression followed by overshoot of R(a) FFA and [FFA] on top of a trend toward basal elevations), that responses after NA are consistent with operation of a glucose-fatty acid cycle in peripheral tissues, and that secondary effects on EGP were through changes in glycogenolysis, not gluconeogenesis.     

Effects of acute cold exposure on rectal temperature, blood glucose and plasma free fatty acids in alloxan-diabetic rats

These experiments were carried out to study the effects of acute cold exposure (0-2 degrees C/4 hr) on rectal temperature, blood glucose and plasma free fatty acids (FFA) in alloxan-diabetic rats. Male Wistar rats weighing 170-190 g were used and diabetes was induced by i.v. alloxan injection (40 mg/kg body wt). Cold exposure produced severe hypothermia in diabetic rats. After 4 hr of cold, blood glucose of diabetic rats was reduced from 296 +/- 16 to 86 +/- 12 mg/dl (P less than 0.01), and FFA increased slightly, but was not statistically different (P greater than 0.05) from the initial value. As expected, interscapular brown adipose tissue (IBAT) and retroperitoneal and epididymal white adipose tissues were significantly lower in diabetic than in control rats. Cold exposure reduced total IBAT lipids in control but not in diabetic animals. The results of this experiment suggest that diabetic rats were unable to maintain body temperature in the cold, probably because of a failure to generate an adequate amount of heat by nonshivering thermogenesis in brown adipose tissue.     

Effects of stimulation and damage of afferent nerves on the glucose and free fatty acid levels in the rat blood under various glycemic conditions

Capsaicin stimulation of afferent neurones increased hyperglycaemic responses to glucose and decreased hypoglycaemia in control rats. Elevation of the free fatty acids level occurred following both the stimulation alone and that combined with insulin. Neonatal capsaicin pre-treatment decreased the hypoglycaemic response effect of insulin and the FFA level. Treatment of adult rats with capsaicin did not affect hypoglycaemia following insulin administration but did decrease the FFA level. In capsaicin pre-treated rats, the capsaicin stimulation exerted no effect upon the hypoglycaemia following insulin administration but abolished the insulin effect on the FFA level. The findings suggest that the capsaicin-sensitive nerves play a major role in mediating the glucose and the FFA metabolic responses.     

Tesaglitazar, a dual PPAR{alpha}/{gamma} agonist, ameliorates glucose and lipid intolerance in obese Zucker rats

Insulin resistance, impaired glucose tolerance, high circulating levels of free fatty acids (FFA), and postprandial hyperlipidemia are associated with the metabolic syndrome, which has been linked to increased risk of cardiovascular disease. We studied the metabolic responses to an oral glucose/triglyceride (TG) (1.7/2.0 g/kg lean body mass) load in three groups of conscious 7-h fasted Zucker rats: lean healthy controls, obese insulin-resistant/dyslipidemic controls, and obese rats treated with the dual peroxisome proliferator-activated receptor alpha/gamma agonist, tesaglitazar, 3 mumol.kg(-1).day(-1) for 4 wk. Untreated obese Zucker rats displayed marked insulin resistance, as well as glucose and lipid intolerance in response to the glucose/TG load. The 2-h postload area under the curve values were greater for glucose (+19%), insulin (+849%), FFA (+53%), and TG (+413%) compared with untreated lean controls. Treatment with tesaglitazar lowered fasting plasma glucose, improved glucose tolerance, substantially reduced fasting and postload insulin levels, and markedly lowered fasting TG and improved lipid tolerance. Fasting FFA were not affected, but postprandial FFA suppression was restored to levels seen in lean controls. Mechanisms of tesaglitazar-induced lowering of plasma TG were studied separately using the Triton WR1339 method. In anesthetized, 5-h fasted, obese Zucker rats, tesaglitazar reduced hepatic TG secretion by 47%, increased plasma TG clearance by 490%, and reduced very low-density lipoprotein (VLDL) apolipoprotein CIII content by 86%, compared with obese controls. In conclusion, the glucose/lipid tolerance test in obese Zucker rats appears to be a useful model of the metabolic syndrome that can be used to evaluate therapeutic effects on impaired postprandial glucose and lipid metabolism. The present work demonstrates that tesaglitazar ameliorates these abnormalities and enhances insulin sensitivity in this animal model.     

Diurnal variations in the catecholamine content in rat tissues. Effects of exogenous noradrenaline

Endogenous noradrenaline (NA) content of the interscapular brown adipose tissue (IBAT), and of the hypothalamus, as well as adrenaline (A) and NA content of the adrenals were measured in the morning and in the evening in rats treated with saline (controls) or with NA (1.6 mg kg-1 pp). NA content in IBAT and in hypothalamus of control animals varies diurnally. NA content in IBAT was significantly higher in the evening than in the morning. In the hypothalamus, these variations were different of those found in the IBAT. Exogenous NA applied both in the morning and in the evening increases significantly NA content in IBAT both in the morning and in the evening, but more in the evening. Unlike IBAT, NA content of the hypothalamus after NA administration does not change essentially. In the adrenal gland of control rats, A content only is changed during the day, being markedly lower in the evening. After NA injection both A and NA are not changed significantly.     

Involvement of nitric oxide in noradrenaline-induced changes in the activity of antioxidant enzymes and lipid peroxidation in rat brown adipose tissue and heart

The effect of exogenous noradrenaline (NA) (1.6 mg.kg(-1) i.p., 35 min prior sacrifice) on the activity of antioxidant enzymes (AOE) copper zinc superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD) and catalase (CAT), as well as lipid peroxides (LP) concentration were studied in the rat interscapular brown adipose tissue (IBAT) and heart of saline (controls) and N(omega)-nitro-L-arginine methyl ester (L-NAME) treated rats (10 mg.kg(-1), i.p., during 3 days and 20 min before NA). NA differently affects both AOE activities and LP production in the IBAT and heart. Thus, NA inhibited the activity of all IBAT AOE and LP production while in the heart it markedly increased CAT activity only, but had no effect on any of SODs activities and LP concentration. L-NAME, a nitric oxide synthase blocker, completely abolished the NA-induced inhibition of the IBAT AOE and LP production, whereas in the heart it was without effect. In conclusion, these results indicate that both NA and L-NAME effects on AOE activity and LP production are tissue specific and also suggest that nitric oxide mediates the NA-induced inhibition of AOE activity and LP production in the IBAT only.     

Relationship between hypothalamic noradrenergic activity and the sympathetic activity in interscapular brown adipose tissue after cold-swim stress in rats.

Noradrenaline (NA) activities in both hypothalamus and interscapular brown adipose tissue (IBAT) were simultaneously assessed before and after cold-swim stress in rats. The technique of gas chromatography-mass spectrometry was employed for the analysis of NA and its primary neuronal metabolite, 3,4-dehydroxy-phenylethylenglycol (DHPG), and the ratio of DHPG to NA was used as an index of NA activity. The ratios of DHPG/NA in both hypothalamus and IBAT were significantly elevated 5 and 20 min after cold-swim stress. Moreover, we found that there is a highly significant positive relationship between the hypothalamic DHPG/NA ratio and the ratio of DHPG/NA in IBAT (r = 0.872, p less than 0.0001). This observation strongly supports the concept in which hypothalamic NA neurons play an important role in modulating the sympathetic outflow.     

Insulin suppresses PDK-4 expression in skeletal muscle independently of plasma FFA

Starvation and experimental diabetes induce a stable increase in pyruvate dehydrogenase kinase (PDK) activity in skeletal muscle, which is largely due to a selective upregulation of PDK-4 expression. Increased free fatty acid (FFA) level has been suggested to be responsible for the upregulation. Because these metabolic states are also characterized by insulin deficiency, the present study was designed to examine whether insulin has a significant effect to regulate PDK mRNA expression in rat skeletal muscle. In study 1, overnight-fasted rats received an infusion of saline or insulin for 5 h (n = 6 each). During the insulin infusion, plasma glucose was clamped at basal levels (euglycemic hyperinsulinemic clamp). A third group (n = 6) received Intralipid infusion during the clamp to prevent a fall in plasma FFA. PDK-2 mRNA level in gastrocnemius muscle was not altered by insulin or FFA (i.e., Intralipid infusion). In contrast, PDK-4 mRNA level was decreased 72% by insulin (P < 0.05), and Intralipid infusion prevented only 20% of the decrease. PDK-4 protein level was decreased approximately 20% by insulin (P < 0.05), but this effect was not altered by Intralipid infusion. In study 2, overnight-fasted rats were refed or received an infusion of saline or nicotinic acid (NA, 30 micromol/h) for 5 h (n = 5 each). During the refeeding and NA infusion, plasma FFA levels were similarly (i.e., 60-70% vs. saline control) lowered. Muscle PDK-4 mRNA level decreased 77% after the refeeding (P < 0.05) but not after the NA infusion. In conclusion, the present data indicate that insulin had a profound effect to suppress PDK-4 expression in skeletal muscle and that, contrary to previous suggestions, circulating FFA had little impact on PDK-4 mRNA expression, at least within 5 h.     

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.     

Uptake of glucose and release of fatty acids and glycerol by rat brown adipose tissue in vivo

The net in vivo uptake or release of free fatty acids glycerol, glucose, lactate, and pyruvate by the interscapular brown adipose tissue (IBAT) of barbital-anesthetized, cold-acclimated rats was determined from measurements of plasma arteriovenous concentration differences across IBAT and tissue blood flow. Measurements were made without stimulation of the tissue and also during submaximal and maximal stimulation by infused noradrenaline (NA), the physiological activator of BAT thermogenesis. There was no appreciable uptake of glucose or release of fatty acids and glycerol by the nonstimulated tissue. At both levels of stimulation there was significant uptake of glucose (1.7 and 2.0 mumol/min) and release of glycerol (0.9 and 1.2 mumol/min), but only at maximal stimulation was there significant release of fatty acids (1.9 mumol/min). Release of lactate and pyruvate accounted for 33% of the glucose taken up at submaximal stimulation and 88% at maximal stimulation. By calculation, the remainder of the glucose taken up was sufficient to have fueled about 12% of the thermogenesis at submaximal stimulation, but only about 2% at maximal stimulation. As estimated from the rate of glycerol release, the rate of triglyceride hydrolysis was sufficient at submaximal stimulation to fuel IBAT thermogenesis entirely with the resulting fatty acids, but it was not sufficient to do so at maximal stimulation when some of the fatty acid was exported. It is suggested that at maximal NA-induced thermogenesis a portion of lipolysis proceeded only to the level of mono- and di-glycerides with the result that glycerol release did not fully reflect the rate of fatty acid formation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Metabolic effects of estrogen substitution in combination with targeted exercise training on the therapy of obesity in ovariectomized Wistar rats

Postmenopausal women tend to have a higher risk in developing obesity and thus metabolic syndrome. Recently we could demonstrate that physical activity and estrogen replacement are effective strategies to prevent the development of nutritional induced obesity in an animal model. The aim of this study was to determine the combined effects of estrogen treatment and exercise training on already established obesity. Therefore ovariectomized (OVX) and sham-operated (SHAM) female Wistar rats were exposed to a high fat diet for ten months. After this induction period obese SHAM and OVX rats either remained sedentary or performed treadmill training for six weeks. In addition OVX rats were treated with 17β-Estradiol (E(2)) alone, or in combination with training. Before and after intervention effects on lipid and glucose metabolism were investigated. Training resulted in SHAM and OVX rats in a significant decrease of body weight, subcutaneous and visceral body fat, size of adipocytes and the serum levels of leptin, cholesterol, low-density lipoprotein and triglycerides. In OVX animals E(2) treatment resulted in similar effects. Often the combination of E(2) treatment and training was most effective. Analysis of the respiratory quotient indicates that SHAM animals had a better fat burning capacity than OVX rats. There was a tendency that training in SHAM animals and E(2) treatment in OVX animals could improve this capacity. Analysis of glucose metabolism revealed that obese SHAM animals had higher glucose tolerance than OVX animals. Training improved glucose tolerance in SHAM and OVX rats, E(2) treatment in OVX rats. The combination of both was most effective. Our results indicate that even after a short intervention period of six weeks E(2) treatment and exercise training improve parameters related to lipid as well as glucose metabolism and energy expenditure in a model of already established obesity. In conclusion a combination of hormone replacement therapy and exercise training could be a very effective strategy to encourage the therapy of diet-induced obesity and its metabolic consequences in postmenopausal women.     

Continuous 24-h nicotinic acid infusion in rats causes FFA rebound and insulin resistance by altering gene expression and basal lipolysis in adipose tissue

Nicotinic acid (NA) has been used as a lipid drug for five decades. The lipid-lowering effects of NA are attributed to its ability to suppress lipolysis in adipocytes and lower plasma FFA levels. However, plasma FFA levels often rebound during NA treatment, offsetting some of the lipid-lowering effects of NA and/or causing insulin resistance, but the underlying mechanisms are unclear. The present study was designed to determine whether a prolonged, continuous NA infusion in rats produces a FFA rebound and/or insulin resistance. NA infusion rapidly lowered plasma FFA levels (>60%, P < 0.01), and this effect was maintained for ≥5 h. However, when this infusion was extended to 24 h, plasma FFA levels rebounded to the levels of saline-infused control rats. This was not due to a downregulation of NA action, because when the NA infusion was stopped, plasma FFA levels rapidly increased more than twofold (P < 0.01), indicating that basal lipolysis was increased. Microarray analysis revealed many changes in gene expression in adipose tissue, which would contribute to the increase in basal lipolysis. In particular, phosphodiesterase-3B gene expression decreased significantly, which would increase cAMP levels and thus lipolysis. Hyperinsulinemic glucose clamps showed that insulin's action on glucose metabolism was improved during 24-h NA infusion but became impaired with increased plasma FFA levels after cessation of NA infusion. In conclusion, a 24-h continuous NA infusion in rats resulted in an FFA rebound, which appeared to be due to altered gene expression and increased basal lipolysis in adipose tissue. In addition, our data support a previous suggestion that insulin resistance develops as a result of FFA rebound during NA treatment. Thus, the present study provides an animal model and potential molecular mechanisms of FFA rebound and insulin resistance, observed in clinical studies with chronic NA treatment.     

Metabolic responses to catecholamines in dogs injected with a single dose of triiodothyronine.

Lipolytic and glycogenolytic responses to catecholamine infusions were studied in resting dogs before and 20 h following administration of a single dose (0.1 mg/kg) of triiodothyronine (T3). In the dogs pretreated with T3 much higher increases in the plasma FFA concentration were found both during noradrenaline and adrenaline infusions in comparison with control experiments. Adrenaline-induced increases in blood LA and glucose levels were also significantly higher in T3-pretreated dogs than in controls. The blockade of beta-adrenergic receptors with propranolol prevented the increases in blood FFA and LA concentrations during subsequent adrenaline infusion. Phentolamine -- the alpha-adrenergic blocking agent -- infused to the T3-pretreated dog inhibited the adrenaline-induced rise in blood glucose level. The observed changes in the metabolic responses to catecholamines induced by triiodothyronine pretreatment indicate that at least in the dog this hormone potentiates both the lipolytic and glycogenolytic effects of catecholamines acting on appropriate adrenergic receptors.     

Effect of 36-hour starvation on in vivo amino acid and glucose uptake by rat brown adipose tissue

The effect of 36-hour starvation on the net uptake/release of amino acids and glucose by interscapular brown adipose tissue (IBAT) of the rat has been studied by means of the determination of the arterio-venous differences in their blood concentrations. Starvation induced a net release of non-essential amino acids by the tissue, mainly alanine, glutamine, glycine and citrulline. In food deprived animals there was not a net glucose uptake by the IBAT. The results obtained in this study are in accordance with a typical peripheral tissue metabolic pattern of IBAT under food deprivation situations.     

Progressive enhancement of body temperature responses to consecutive exercise-bouts of the same intensity in dogs

Progressive enhancement of body temperature responses to consecutive exercise-bouts of the same intensity in dogs. Acta physiol. pol., 1985, 36 (3): 165-174. Changes in rectal (Tre), muscle (Tm), and hypothalamic (Thy) temperatures, plasma osmolality, and some intermediary metabolic variables were examined in dogs performing four successive exercise-bouts of the same intensity. During the rest-intervals separating the exercise-bouts body temperatures returned to initial levels and water losses were replaced. Tm and Tre responses to consecutive exercise-bouts were progressively increasing. Similar tendency was found in Thy changes. Cardiac and respiratory frequencies attained the same levels in all four exercise-bouts, while blood lactate and FFA concentrations were increasing and blood glucose level was decreasing progressively. No changes in plasma osmolality was noted. Exercise-induced increases in Tm correlated positively with plasma FFA concentration (r = 0.68). Body temperature responses to exercise were reduced by beta-adrenergic blockade. It is concluded that the enhancement of the thermal responses to consecutive exercise-bouts can be related to the metabolic action of catecholamines.     

Effect of the acute crowding stress on the rat brown adipose tissue metabolic function

Our previous results have shown that metabolic and thermal stressors influence interscapular brown adipose tissue (IBAT) metabolic activity by increasing oxygen consumption and, consequently, altering the toxic reactive oxygen species (ROS) production and the antioxidative system activity. Since there is not enough evidence about the effect of psychosocial stressors on these processes, we studied the effect of acute crowding stress on the IBAT and hypothalamic monoamine oxidase (MAO) activity as well as IBAT antioxidative enzymes, manganese (MnSOD), copper-zinc superoxide dismutase (CuZnSOD) and catalase (CAT), as the relevant indicators of IBAT metabolic alternations under the stress exposure and the returning of animals to control conditions. The results indicated that acute crowding stress did not change the hypothalamic and IBAT MAO activities, the generation of ROS and, consequently, the IBAT CuZnSOD and CAT activities. However, all three antioxidative enzymes were affected only after the recovery period. It seems that peripheral overheating of rats during acute crowding changes the stress nature, by becoming more thermal than psychosocial and by suppression the hypothalamic efferent pathways involved in the IBAT thermogenesis regulation. However, it seems that returning of the animals to the control conditions after the stress termination causes the reactivation of IBAT thermogenesis with tendency to normalise the body temperature.