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.

Cold-induced developmental changes in fat cell size and number in brown adipose tissue of the rat

1981 ◽  
Vol 240 (4) ◽  
pp. E379-E383 ◽  
Author(s):  
C. Senault ◽  
G. Cherqui ◽  
M. Cadot ◽  
R. Portet
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Acclimation ◽  
Cell Size ◽  
Brown Fat ◽  
Control Group ◽  
Fat Cells ◽  
Fat Cell ◽  
Brown Adipose ◽  
The Mean

Seven-week-old Long-Evans rats were acclimated to a constant temperature of either 28 degrees C (control group) or 5 degrees C (cold-acclimated group). Cold acclimation induced a 70% increase in the interscapular brown adipose tissue (IBAT) relative mass, a 35% increase in DNA content, and a 44% decrease in triglyceride (TG) content, which resulted in a 51% decrease of the TG/DNA ratio. A procedure is described by which brown fat cells were isolated, with a yield of 21% from the IBAT of the control group and of 38% in the cold-acclimated group. In both groups, the brown fat cells accounted for 35-37% of the total cells in the tissue. Cold acclimation induced decreases in the mean fat cell diameter (about 20%), the mean fat cell TG content (50%), and the fat cell TG/DNA ratio (50%). The total number of IBAT fat cells was significantly increased in cold-acclimated rats. It is concluded that cold acclimation involves a hyperplasia of the IBAT, associated with a decrease of fat cell size without any alteration of the fat cell-to-nonfat cell ratio.

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.

Cold acclimation-recruited nonshivering thermogenesis: the Syrian hamster is not an exception

1995 ◽  
Vol 269 (4) ◽  
pp. R767-R774 ◽  
Author(s):  
A. Dicker ◽  
B. Cannon ◽  
J. Nedergaard
Keyword(s):  
Metabolic Rate ◽  
Cold Acclimation ◽  
Resting Metabolic Rate ◽  
High Rate ◽  
In Vivo Studies ◽  
Nonshivering Thermogenesis ◽  
Brown Adipose ◽  
Thermogenic Response

Biochemical evidence from in vitro studies of brown adipose tissue in Syrian hamsters indicates a significant degree of recruitment of the tissue as an effect of cold acclimation. However, earlier in vivo studies indicate a lack of recruitment of nonshivering thermogenesis in the intact animal as a result of cold acclimation. Because of this apparent discrepancy, the occurrence of cold acclimation-recruited nonshivering thermogenesis in hamsters was investigated. Hamsters were cold acclimated to 6 degrees C or remained at 24 degrees C (controls), and their thermogenic response was investigated in an open-circuit system at 24 degrees C. Cold acclimation resulted in a small increase in resting metabolic rate and a major increase in the thermogenic response to norepinephrine (61% increase over resting metabolic rate in controls and 156% increase in cold-acclimated animals). The absolute beta 3-specific adrenergic agonist CGP-12177 also induced a high rate of nonshivering thermogenesis, which was similarly recruited. It was concluded that, concerning the relative effect of recruitment on the capacity for nonshivering thermogenesis, the intact hamsters responded as would be predicted from in vitro experiments. Thus the hamster does not seem to constitute an exception to the general patterns described for other rodents concerning recruitment of nonshivering thermogenesis due to cold acclimation.

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.

cAMP metabolism and lipolysis in brown adipocytes of hamsters consuming a cafeteria diet

1985 ◽  
Vol 248 (2) ◽  
pp. E224-E229
Author(s):  
R. J. Schimmel ◽  
L. McCarthy ◽  
K. K. McMahon
Keyword(s):  
Adenylate Cyclase ◽  
Sympathetic Activity ◽  
Brown Fat ◽  
Adenylate Cyclase System ◽  
Brown Adipocytes ◽  
Beta Adrenergic ◽  
Fat Depots ◽  
Brown Adipose ◽  
Camp Levels ◽  
In Cells

Feeding animals cafeteria diets causes increased sympathetic activity to brown adipose tissue and this is believed to be responsible for the concomitant activation of thermogenesis. Because chronic catecholamine stimulation in other systems leads to a desensitization of beta-adrenergic receptors, we examined lipolysis and cAMP production in brown adipocytes of hamsters eating cafeteria diets for evidence of diminished beta-adrenergic responses. Basal cAMP levels were similar in chow- and cafeteria-fed hamsters. However, adipocytes from overfed animals formed less cAMP in response to isoproterenol than those of control animals. Isoproterenol-stimulated adenylate cyclase activity was similarly decreased in membrane preparations from cafeteria-fed hamsters. However, when the diterpene forskolin was used, equal amounts of cAMP were formed in cells and membrane preparations from control and overfed animals. In contrast to the reduced responses of the cAMP system to isoproterenol stimulation observed in overfed hamsters, isoproterenol-stimulated lipolysis was greater in cells from overfed animals than in cells from control animals. These results are consistent with a desensitization of the adenylate cyclase system in brown adipocytes occurring during chronic hyperphagia. Because eating cafeteria diets has been reported to increase sympathetic activity to brown fat depots, the apparent desensitization of brown adipocytes observed in this study may result from a persistent stimulation of the brown fat with norepinephrine in vivo. Our data also suggest the existence of mechanisms that preserve lipolysis in the face of low cAMP levels.

Normal and Neoplastic Cells of Brown Adipose Tissue Express the Adhesion Molecule CD31

2006 ◽  
Vol 130 (4) ◽  
pp. 480-482 ◽  
Author(s):  
Renato Rosso ◽  
Marco Lucioni
Keyword(s):  
Adipose Tissue ◽  
Adhesion Molecule ◽  
Myxoid Liposarcoma ◽  
Cell Types ◽  
Brown Fat ◽  
Fat Cells ◽  
Neoplastic Cells ◽  
Brown Adipose ◽  
Formalin Fixed Paraffin Embedded ◽  
Well Differentiated

Abstract Context.—CD31 (platelet-endothelial cell adhesion molecule-1; PECAM-1), an adhesion molecule involved in the process of angiogenesis, is used as a marker of normal and neoplastic vascularization. During the assessment of angiogenesis and vascular invasion in a thymic carcinoid tumor, we observed unexpected immunostaining for CD31 in perithymic brown fat nests. Objective.—To determine whether CD31 is expressed by normal and neoplastic cells of brown fat, a tissue whose thermogenetic activity depends heavily on high perfusion. Design.—Formalin-fixed, paraffin-embedded archival tissues were immunostained by the labeled avidin-biotin method using antibodies against CD31 (clones JC70A and 1A10) after retrieval of heat-induced epitopes. Archival tissues included perithymic, periadrenal, axillary, and neck adipose tissue in which were embedded nests of brown fat (n = 15), hibernoma (n = 3), lipoma (n = 6), well-differentiated liposarcoma (n = 4), and myxoid liposarcoma (n = 4). Results.—Invariably, multivacuolated and univacuolated adipocytes of normal brown fat and hibernomas were intensely positive for the CD31 antigen. The immunostaining “decorated” cell membranes and the membranes of intracytoplasmic vacuoles. No expression of CD31 was found in normal adipocytes of white fat, in neoplastic cells of lipomas, or in multivacuolated lipoblasts of well-differentiated and myxoid liposarcomas. Conclusions.—The spectrum of cell types that express CD31 is expanded to include normal and neoplastic brown fat cells. We speculate that the expression of CD31 may play a role in the development and maintenance of the vascular network characterizing this specialized adipose tissue. Moreover, CD31 may inhibit the Bax-mediated apoptosis of brown fat cells. For practical purposes, CD31 may be used as an immunohistochemical marker for distinguishing between white and brown fat and for diagnosing hibernoma in paraffin sections.

Thermogenesis of brown adipose tissue in cold-acclimated rats

1964 ◽  
Vol 206 (1) ◽  
pp. 143-148 ◽  
Author(s):  
Robert E. Smith ◽  
Jane C. Roberts
Keyword(s):  
Spinal Cord ◽  
Adipose Tissue ◽  
Heat Exchange ◽  
Brown Adipose Tissue ◽  
Respiratory Rate ◽  
Cold Acclimation ◽  
Brown Fat ◽  
Brown Adipose

Multilocular brown adipose tissue in the rat is shown to increase in both mass and respiratory rate, in vitro, during cold acclimation. By vascular convection the resulting heat is directly applied to the thoracocervical regions of the spinal cord, the heart, and other thoracic organs. The vasculature is so arranged as to exercise a fine order of thermogenic control over the brown fat and temperature of the peripheral venous returns to the thorax, facilitated in part by a "reverse" type of countercurrent heat exchange apparently not previously described.

Norepinephrine-induced sustained inward current in brown fat cells: α1-mediated by nonselective cation channels

2000 ◽  
Vol 279 (5) ◽  
pp. E963-E977 ◽  
Author(s):  
Ari Koivisto ◽  
Detlef Siemen ◽  
Jan Nedergaard
Keyword(s):  
Fold Increase ◽  
Brown Fat ◽  
Cation Channels ◽  
Current Response ◽  
Fat Cells ◽  
Adrenergic Stimulation ◽  
Open Probability ◽  
Inward Current ◽  
Nonselective Cation Channels ◽  
Sustained Inward Current

The nature of the sustained norepinephrine-induced depolarization in brown fat cells was examined by patch-clamp techniques. Norepinephrine (NE) stimulation led to a whole cell current response consisting of two phases: a first inward current, lasting for only 1 min, and a sustained inward current, lasting as long as the adrenergic stimulation was maintained. The nature of the sustained current was here investigated. It could be induced by the α1-agonist cirazoline but not by the β3-agonist CGP-12177A. Reduction of extracellular Cl− concentration had no effect, but omission of extracellular Ca2+ or Na+ totally eliminated it. When unstimulated cells were studied in the cell-attached mode, some activity of ≈30 pS nonselective cation channels was observed. NE perfusion led to a 10-fold increase in their open probability (from ≈0.002 to ≈0.017), which persisted as long as the perfusion was maintained. The activation was much stronger with the α1-agonist phenylephrine than with the β3-agonist CGP-12177A, and with the Ca2+ionophore A-23187 than with the adenylyl cyclase activator forskolin. We conclude that the sustained inward current was due to activation of ≈30 pS nonselective cation channels via α1-adrenergic receptors and that the effect may be mediated via an increase in intracellular free Ca2+ concentration.

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.

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.

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