The receptors responsible for heat production in brown adipose tissue in the young rabbit

1986 ◽  
Vol 64 (2) ◽  
pp. 133-137 ◽  
Author(s):  
W. H. Harris ◽  
L. A. Moore ◽  
S. Yamashiro
Keyword(s):  
Brown Fat ◽  
Young Rabbit ◽  
Low Doses ◽  
Adrenergic Agonists ◽  
Alpha Adrenoceptors ◽  
Brown Adipose ◽  
Adrenergic Antagonist ◽  
Auxiliary Role ◽  
Stimulation Of ◽  
Thermogenic Response

It is known that adrenergic agonists stimulate thermogenesis in the brown fat of the young rabbit but the receptors responsible for mediating the response have not been identified. The infusion of either noradrenaline or isoproterenol (1–2 μg∙kg−1∙min−1) produced an increase in subcutaneous temperature (0.93 ± 0.15 and 1.22 ± 0.10 °C, respectively over the interscapular brown fat. At low doses (0.4 μg∙kg−1∙min−1) only isoproterenol was effective. The thermogenic response to isoproterenol was blocked by atenolol, a beta1-adrenergic antagonist. Neither salbutamol or terbutaline, both beta2-agonists, produced a temperature increase. Collectively, these data suggest that stimulation of beta1-adrenoceptor is primarily responsible for the thermogenic activity of brown fat in the rabbit. However, it was found that 53% of the increase in temperature could be blocked by prazosin, an alpha1-antagonist. Phentolamine was not effective as a blocker. Although a maximal brown fat thermogenic response can be achieved by stimulating the beta-adernoceptors, the alpha-adrenoceptors appear to play at least an auxiliary role in the young rabbit.

Influence of subdiaphragmatic vagotomy and brown fat sympathectomy on thermogenesis in rats

1985 ◽  
Vol 249 (3) ◽  
pp. E239-E243 ◽  
Author(s):  
P. L. Andrews ◽  
N. J. Rothwell ◽  
M. J. Stock
Keyword(s):  
Insulin Treatment ◽  
Brown Fat ◽  
Guanosine Diphosphate ◽  
Subdiaphragmatic Vagotomy ◽  
Brown Adipose ◽  
Adrenergic Antagonist ◽  
Brown Adipose Tissue Activity ◽  
Acute Injection ◽  
Brown Fat Mitochondria ◽  
Thermogenic Response

Infusion of rats with insulin (8 U/day via implanted minipump) for 7 days caused a 22% rise in resting oxygen consumption, which was inhibited by acute injection of the beta-adrenergic antagonist propranolol. Insulin treatment produced significant increases in brown fat mass, protein content, and total thermogenic activity (assessed from binding of guanosine diphosphate to isolated brown fat mitochondria), but these responses were inhibited by prior surgical sympathectomy of the tissue. Animals subjected to subdiaphragmatic vagotomy gained more weight than pair-fed, sham-operated controls and showed reductions in total energy expenditure, the acute thermogenic response to a meal and brown adipose tissue activity. Daily injections of insulin (1 U/day) prevented all of these effects of vagotomy. These data demonstrate that the changes in brown fat activity induced by exogenous insulin are mediated by the sympathetic nervous system and that the depressed thermogenesis and brown fat activity associated with vagotomy appear to be due to a relative insulin deficiency and can be reversed by treatment with the hormone.

Effect of norepinephrine and uncoupling agents on brown adipose tissue

1968 ◽  
Vol 46 (6) ◽  
pp. 897-902 ◽  
Author(s):  
Barbara A. Horwitz ◽  
Paul A. Herd ◽  
Robert Emrie Smith
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Brown Fat ◽  
Brown Adipose ◽  
In Vitro Response ◽  
Stimulation Of ◽  
Thermogenic Response

Examination of the in vivo effect of 2,4-dinitrophenol (DNP) on the brown adipose tissue of cold-exposed rats, as well as the in vitro response of this tissue to DNP and dicumarol, indicates that brown fat does possess a functional electron transport coupled phosphorylating system. Moreover, the fact that a norepinephrine-induced thermogenic response (in vivo) can be elicited from the brown fat after DNP administration implies that the effect of norepinephrine (NE) is not primarily due either to a physiological uncoupling by fatty acids, the level of which is increased by NE, or to stimulation of an ATP-ase system. Alternatively, our data suggest that under basal conditions (i.e. when the animal is not stimulated by cold stress or NE), the heat production (oxygen consumption) of the brown fat is limited by the availability of substrate rather than ADP. It is thus proposed that the thermogenic effect of NE results from the stimulation of lipolysis and an attendant increase of substrate available for oxidation.

Role of mast cell histamine in brown adipose tissue thermogenic response to VMH stimulation

1994 ◽  
Vol 266 (3) ◽  
pp. R831-R837 ◽  
Author(s):  
M. Desautels ◽  
A. Wollin ◽  
I. Halvorson ◽  
D. V. Muralidhara ◽  
J. Thornhill
Keyword(s):  
Adipose Tissue ◽  
Mast Cells ◽  
Brown Adipose Tissue ◽  
Receptor Antagonist ◽  
Histamine Content ◽  
Hypothalamic Area ◽  
Neural Input ◽  
Brown Adipose ◽  
Stimulation Of ◽  
Thermogenic Response

Electrical stimulation of the ventromedial hypothalamic area in rats caused a significant but transient increase in interscapular brown adipose tissue temperature. This response was markedly reduced by cimetidine, a histamine H2-receptor antagonist, but not by pyrilamine, an H1-receptor antagonist. Histamine is present in substantial amounts within mast cells in brown adipose tissue as injections of compound 48/80, which cause degranulation of connective tissue mast cells, reduced the tissue histamine content by > 85%. In contrast, histamine content in brown adipose tissue was not affected by loss of sympathetic neural input (with 6-hydroxydopamine) or sensory neural input (with capsaicin). Neither cimetidine nor histamine had any effect on basal and norepinephrine-stimulated rates of O2 consumption by isolated brown adipocytes. These results indicate that histamine released from mast cells acting on H2-receptors may play an important but indirect role in the thermogenic response of brown adipose tissue to stimulation of the ventromedial hypothalamic area.

scholarly journals Cold-induced reduction in Giα proteins in brown adipose tissue. Effects on the cellular hypersensitization to noradrenaline caused by pertussis-toxin treatment

1996 ◽  
Vol 314 (3) ◽  
pp. 761-768 ◽  
Author(s):  
Petr SVOBODA ◽  
Lena UNELIUS ◽  
Andrea DICKER ◽  
Barbara CANNON ◽  
Graeme MILLIGAN ◽  
...  
Keyword(s):  
Cold Acclimation ◽  
Pertussis Toxin ◽  
Fold Increase ◽  
Brown Fat ◽  
Fat Cells ◽  
Brown Adipose ◽  
Increased Sensitivity ◽  
Gi Proteins ◽  
Thermogenic Response ◽  
In Cells

The significance of Gi proteins for the physiological desensitization phenomena observed in brown-fat cells from cold-acclimated hamsters was investigated. For this purpose, pertussis toxin (the inhibitor of Gi function) was injected into control and cold-acclimated hamsters. After 3 days the thermogenic response to noradrenaline injection was monitored in the intact animals. It was found that the pertussis-toxin pretreatment did not affect the thermogenic response to noradrenaline. Nonetheless, the pertussis toxin pretreatment had a dramatic effect on the noradrenaline-sensitivity of isolated brown-fat cells (measured the following day as the respiratory response): a 250-fold-increased sensitivity to noradrenaline was observed in cells from control animals that had been pertussis-toxin pretreated. However, only a 20-fold increase was observed in cells from cold-acclimated hamsters, implying a lower complement of the Gi system in these cells. Therefore the content of Gi proteins was determined by quantitative immunoblotting of purified plasma-membrane proteins. Cold acclimation resulted in a nearly 50% reduction in the content of Gi1α and Gi2α, as well as of the β-subunit, both when expressed on a protein basis and when related to the content of forskolin-stimulated adenylyl cyclase; when expressed per unit of [3H]ouabain-binding (Na+/K+-ATPase), the reduction was even higher. In view of the magnitude of the pertussis-toxin effect, it was concluded that Gi proteins must play a substantial role in the regulation of the response of brown-fat cells to noradrenaline. As the capacity of the Gi pathway is reduced rather than augmented during cold acclimation, Gi activity cannot be responsible for the desensitization to noradrenaline observed in cells from cold-acclimated animals. However, the reduced Gi content may explain the earlier observed desensitization to adenosine that occurs after acclimation to cold.

The relationship between the thermogenic response of brown adipose tissue and age during noradrenaline infusion in the young rabbit

1985 ◽  
Vol 63 (10) ◽  
pp. 1215-1220
Author(s):  
W. H. Harris ◽  
D. O. Foster ◽  
B. E. Nadeau
Keyword(s):  
Blood Flow ◽  
Oxygen Consumption ◽  
Age Groups ◽  
Brown Fat ◽  
Young Rabbit ◽  
Morphological Evidence ◽  
Response Curves ◽  
Total Blood ◽  
Noradrenaline Infusion ◽  
Brown Adipose

This work was undertaken to determine if the thermogenic activity of brown fat decreased with age in young rabbits despite the morphological evidence indicating persistence of the brown adipocytes at 4 weeks of age. Data obtained by infusing five doses of noradrenaline and measuring oxygen consumption were used to construct cumulative dose–response curves for five age groups between 3 and 32 days of age. Blood flow to brown fat and other tissues was measured by the microsphere method at 1 and 3 weeks of age. The noradrenaline-induced increase in oxygen consumption when expressed as a percentage of resting oxygen consumption in millilitres per 100 g of body weight decreased (p < 0.05) with age. However, the absolute noradrenaline-induced increase in metabolic rate (millilitres per minute) increased with age. Total blood flow to brown fat (millilitres per minute) during noradrenaline infusion was unchanged between 1 and 3 weeks of age, but when the blood flow was expressed in millilitres per minute per gram of tissue flow decreased significantly (p < 0.05) probably because of infiltration of brown fat with white fat. These data suggest that the amount of brown fat and its thermogenic capacity remain relatively constant between 1 and 3 weeks of age, but as a thermogenic organ, brown fat becomes proportionally less effective with age because of the large increase in body mass.

Apparent thermogenic effect of injected glucagon is not due to a direct effect on brown fat cells

1998 ◽  
Vol 275 (5) ◽  
pp. R1674-R1682 ◽  
Author(s):  
Andrea Dicker ◽  
Jin Zhao ◽  
Barbara Cannon ◽  
Jan Nedergaard
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Brown Fat ◽  
Fat Cells ◽  
Brown Adipose ◽  
Adrenergic Blocker ◽  
Vehicle Injection ◽  
Alternative Means ◽  
Glucagon Injection ◽  
Thermogenic Response

To examine the significance of brown adipose tissue for the thermogenic response to glucagon, we injected glucagon intraperitoneally into rats (that have glucagon-sensitive brown fat cells) and into hamsters (that have glucagon-insensitive brown fat cells). Although a thermogenic response to glucagon injection was apparently observed in rats, this response was not augmented by cold acclimation and was not dose dependent. Similar observations were made in hamsters. The thermogenic response could be fully blocked by prior injection of the β-adrenergic blocker propranolol. Thus no direct thermogenic response to injected glucagon could be demonstrated, and the thermogenic response observed was fully due to vehicle injection. However, glucagon injection was able to unmask mitochondrial [3H]GDP binding. As expected, isolated brown fat cells from rats and mice responded thermogenically to glucagon but brown fat cells from hamsters were unresponsive. The EC50 of the rat brown fat cells was high (5 nM); these cells also responded to secretin, with an EC50 of 22 nM. It was concluded that, in contrast to earlier observations, no thermogenic response to injected glucagon could be observed; this may be related to differences in glucagon preparations. Brown fat cells from certain species are, however, glucagon sensitive. It is uncertain whether glucagon is the endogenous agonist for these receptors, but the presence of the glucagon-responsive receptor indicates alternative means to norepinephrine for stimulation of brown adipose tissue thermogenesis and, probably, of recruitment.

Surgical removal of brown fat results in rapid and complete compensation by other depots

1989 ◽  
Vol 257 (2) ◽  
pp. R253-R258 ◽  
Author(s):  
N. J. Rothwell ◽  
M. J. Stock
Keyword(s):  
Cytochrome Oxidase ◽  
Body Weight Gain ◽  
Young Male ◽  
Brown Fat ◽  
Male Rats ◽  
Surgical Removal ◽  
Brown Adipose ◽  
Response Increase ◽  
Excised Tissue ◽  
Thermogenic Response

Interscapular, scapular, and cervical brown adipose tissue (BAT) depots were removed from young male rats (BATX). These depots represented 40% of both the total dissectible mass and cytochrome oxidase content of BAT in these animals. Sham-operated and BATX rats were fed a low (8%) protein diet for periods of 9 or 16 days. Over both periods, body weight gain and energy intake, gain, expenditure, and efficiency were almost identical in sham and BATX groups. Four days after lipectomy the maximal thermogenic response (increase in O2 consumption) to norepinephrine (400 micrograms/kg sc) was 30% lower for BATX rats than for controls, but by day 13 this difference had disappeared. Nine days after lipectomy the total mass and cytochrome oxidase activity of the remaining dissectible BAT was comparable to that of the sham-operated controls, although the protein content was slightly reduced. The specific mitochondrial GDP binding (an index of thermogenic activity) was increased significantly in BATX rats, and total BAT mitochondrial GDP binding was no different from control values. At the end of the experiment (day 16), no regeneration of excised tissue had occurred, but the remaining BAT depots had shown almost complete compensation; the mass and the oxidative and thermogenic capacity of the total dissectible brown fat were virtually identical in both groups.

Potentiation of in vivo thermogenesis in rat brown adipose tissue by stimulation of α1-adrenoreceptors is associated with increased release of cyclic AMP

1984 ◽  
Vol 62 (8) ◽  
pp. 943-948 ◽  
Author(s):  
Stephanie W. Y. Ma ◽  
David O. Foster
Keyword(s):  
Adipose Tissue ◽  
Cyclic Amp ◽  
Brown Adipose Tissue ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Plasma Camp ◽  
Na Release ◽  
Stimulation Of ◽  
Thermogenic Response

Release of cyclic AMP (cAMP) from the interscapular brown adipose tissue (IBAT) of barbital-anesthetized, cold-acclimated rats given activators and inhibitors of brown adipose tissue (BAT) thermogenesis was assessed by measuring IBAT blood flow (microsphere method) and the arteriovenous difference in plasma cAMP across the tissue. The release was taken as an index of the generation of cAMP in the IBAT. During thermogenesis induced by infusion of graded doses of noradrenaline (NA), release of cAMP increased from no significant release without NA to 68 pmol/min at a NA dose that effected maximal thermogenesis. The α-adrenoreceptor antagonist dihydroergotoxin inhibited NA-induced BAT thermogenesis and markedly reduced the release of cAMP. The α1-adrenoreceptor agonist phenylephrine potentiated the in vivo thermogenic response of BAT to isoproterenol or to a suboptimal dose of NA and enhanced the release of cAMP elicited by these catecholamines. But given alone, phenylephrine or dihydroergotoxin had very little or no effect on thermogenesis and cAMP release. These results suggest that stimulation of the α1-adrenoreceptors on BAT adipocytes potentiates the thermogenic response originating from stimulation of the adenylate cyclase-coupled β1-adrenoreceptors by increasing, in some indirect way, the generation of cAMP, the intracellular messenger for activation of thermogenesis. However, in the absence of proof that adipocytes are the principal source of the cAMP released from IBAT, during catecholamine-induced thermogenesis, this explanation for the effect of α1-adrenoreceptor stimulation on thermogenesis remains tentative.

Arotinolol is a weak partial agonist on β3-adrenergic receptors in brown adipocytes

2001 ◽  
Vol 79 (7) ◽  
pp. 585-593 ◽  
Author(s):  
Jin Zhao ◽  
Valeria Golozoubova ◽  
Barbara Cannon ◽  
Jan Nedergaard
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Adrenergic Receptor ◽  
Partial Agonist ◽  
Brown Fat ◽  
Fat Cells ◽  
Direct Stimulation ◽  
Brown Adipose ◽  
Adrenergic Antagonist ◽  
Low Sensitivity

Arotinolol, a clinically used α/β-adrenergic blocker, has been demonstrated to be an anti-obesity agent. The anti-obesity effect of arotinolol was suggested to be the result of direct activation of thermogenesis in brown-fat cells. We tested the ability of arotinolol to stimulate thermogenesis (oxygen consumption) in isolated brown-fat cells and in intact animals. Arotinolol stimulated thermogenesis in brown-fat cells isolated from mouse and hamster. A relatively low sensitivity to the β-adrenergic antagonist propranolol (pKB [Formula: see text] 6) indicated that arotinolol interacted with the β3-adrenergic receptor. On the β3-receptor, arotinolol was a very weak (EC50 [Formula: see text] 20 µM) and only partial ([Formula: see text]50 %) agonist, but arotinolol also demonstrated the properties of being a β3-receptor antagonist with a pKB of 5.7. In intact animals, only the antagonistic action of arotinolol could be observed. Because arotinolol is only a very weak and partial agonist on the β3-receptors, direct stimulation of thermogenesis in brown adipose tissue is unlikely to be sufficient to cause significant weight loss. It may be necessary to invoke additional pathways to explain the anti-obesity effects of chronic treatment with arotinolol.Key words: arotinolol, β3-adrenergic receptor, brown adipose tissue, thermogenesis, mouse, hamster, rat.

Evidence for a contribution by brown adipose tissue to the development of fever in the young rabbit

1985 ◽  
Vol 63 (6) ◽  
pp. 595-598 ◽  
Author(s):  
W. H. Harris ◽  
D. O. Foster ◽  
B. E. Nadeau
Keyword(s):  
Blood Flow ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Heat Production ◽  
Brown Fat ◽  
Young Rabbit ◽  
Tissue Blood Flow ◽  
Febrile Response ◽  
Arterial Blood ◽  
Brown Adipose

This study was undertaken to determine if brown adipose tissue was involved in heat production during fever produced by S. abortus equi (1 μg) in unanesthetized rabbits aged 19–26 days. The fever (0.9–1.6 °C) occurred after a delay of 20–30 min and was frequently biphasic. Radiolabelled microspheres for measuring tissue blood flow were injected intraventricularly into three groups of animals: rabbits not given pyrogen, rabbits in which the febrile response to pyrogen was developing, and rabbits in which the febrile response had peaked. Blood flow to brown fat deposits and other organs was calculated from the fractional distribution of the microspheres and the recovery of microspheres in a reference arterial blood sample. At the fever peak, blood flow to brown fat was not significantly different (p > 0.05) from the control value (0.9 ± 0.2), but during the rising phase of the fever the flow increased significantly (p < 0.01) to 2.6 ± 0.4 mL min−1 g−1. The blood flow to muscles of the forelimbs and hind limbs was also increased significantly (p < 0.05) during the rising phase of the fever. No significant change in blood flow to other organs or tissues was found during the rising phase of the fever. These results indicate that both nonshivering as well as shivering thermogenesis contribute to heat production during development of fever in the young rabbit. However, nonshivering thermogenesis was not involved in the maintenance of the elevated body temperature after the fever had peaked.

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