High affinity GDP binding sites on brown adipose tissue mitochondria of genetically obese ‘fa/fa’ rats

1985 ◽  
Vol 5 (2) ◽  
pp. 159-166 ◽  
Author(s):  
R. R. French ◽  
S. J. Holt ◽  
D. A. York
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Binding Sites ◽  
Equilibrium Dialysis ◽  
Affinity Binding ◽  
High Affinity ◽  
Brown Adipose ◽  
Obese Rats

The number of high affinity [3H]GDP binding sites in brown adipose tissue mitochondria is normal in obese (f a / f a) rats in contrast to the reduced number of low affinity GDP binding sites. Adrenalectomy corrected the loss of low affinity binding sites in fa/fa rats but had no effect on the number of high affinity sites in either lean or obese rats. Equilibrium dialysis was used to show the presence of both high and low affinity binding sites on the purified 32 kdalton protein.

Are there one or two high-affinity binding sites for GDP in brown adipose tissue mitochondria?

1986 ◽  
Vol 14 (6) ◽  
pp. 1201-1202
Author(s):  
RACHEL E. MILNER ◽  
SHELAGH WILSON ◽  
JONATHAN R. S. ARCH ◽  
PAUL TRAYHURN
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Binding Sites ◽  
Affinity Binding ◽  
High Affinity Binding ◽  
High Affinity ◽  
Brown Adipose

scholarly journals Evidence for masking of brown adipose tissue mitochondrial GDP-binding sites in response to fasting in rats made obese by dietary manipulation. Effects of reversion to standard diet

1991 ◽  
Vol 279 (2) ◽  
pp. 575-579 ◽  
Author(s):  
P Puigserver ◽  
I Lladó ◽  
A Palou ◽  
M Gianotti
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Binding Sites ◽  
Uncoupling Protein ◽  
Cafeteria Diet ◽  
Standard Diet ◽  
Dietary Manipulation ◽  
Bat Mitochondria ◽  
Brown Adipose ◽  
Obese Rats

A specific immunoassay of uncoupling protein (UCP) and measurement of GDP binding were used to study the chronic responses of brown adipose tissue (BAT) mitochondria from rats made obese by dietary means (cafeteria rats) and from obese rats subsequently fed a standard diet (post-cafeteria rats). We studied the response to fasting in order to assess the masking/unmasking responses in these groups. These studies have shown the following. (1) In the obese rats (cafeteria and post-cafeteria) the chronic increase in mitochondrial UCP concentration compared with controls parallels the increase in GDP binding. (2) In 24 h-fasted control rats the decrease in GDP binding is associated with a change in UCP concentration, but in fasting cafeteria and post-cafeteria obese rats the decrease in GDP binding is not associated with any change in UCP concentration. (3) Post-cafeteria obese rats showed increased GDP binding and higher UCP concentrations than the controls, but these values were less than in cafeteria obese rats. (4) Control rats at 8 months old showed greater GDP binding and had a higher UCP concentration than 11-month-old control rats. (5) The responses of GDP binding and UCP concentration to fasting in post-cafeteria obese rats were similar to those in cafeteria obese rats, suggesting that such abbreviations are related to the obese status itself rather than to the composition of the cafeteria diet. The evidence supports the hypothesis that the response of the cafeteria and post-cafeteria obese rats to fasting is associated with a masking of UCP, whereas with chronic manipulation of diet changes in UCP concentration predominate.

Acute influences on the two GDP-binding sites in brown-adipose-tissue mitochondria

1984 ◽  
Vol 4 (6) ◽  
pp. 523-533 ◽  
Author(s):  
K. R. Bryant ◽  
N. J. Rothwell ◽  
M. J. Stock
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Conformational Changes ◽  
Binding Sites ◽  
Dissociation Constants ◽  
Mitochondrial Protein ◽  
Scatchard Analysis ◽  
Slight Reduction ◽  
High Affinity ◽  
Brown Adipose

Scatchard analysis of3H-guanosine diphosphate (GDP) binding to rat brown-adipose-tissue mitochondria demonstrated that binding to the high- and low-affinity sites (Kd = 0.05 and 2.0 μM) was abolished by denaturation at 100°C but non-specific binding remained constant (0.2% of free-GDP). Prior incubation of mitochondria at 37°C reduced binding to the high-affinity site, but this could be reversed by incubating samples at 0°C. Addition of palmitic acid (5–40 nmole/mg of mitochondrial protein) did not affect GDP-binding, but similar concentrations of palmitoyl CoA caused a slight reduction in the number of high-affinity sites and a significant decrease in the number of lower-affinity sites. Acute treatments known to stimulate thermogenesis in vivo (a single meal, cold exposure, or noradrenaline injection 40–80 min before sacrifice) all increased binding to both binding sites, and tended to raise the dissociation constants, whereas injection of 2-deoxy-D-glucose, which depresses metabolic rate in the rat, decreased dissociation constants of both sites and the maximum number of high-affinity sites. These data indicate that both GDP-binding sites respond rapidly to acute thermogenic stimuli, possibly due to conformational changes in the mitochondrial inner membrane, and that palmitoyl CoA may influence mitochondrial proton conductance via an association with purine nucleotide binding sites.

scholarly journals The effect of adrenalectomy on GDP binding to brown-adipose-tissue mitochondria of obese rats

1982 ◽  
Vol 208 (3) ◽  
pp. 819-822 ◽  
Author(s):  
Susan Holt ◽  
David A. York
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Binding Sites ◽  
Zucker Rats ◽  
Lean Control ◽  
Brown Adipose ◽  
Obese Rats ◽  
Number Of Binding Sites ◽  
Obese Zucker Rats

GDP binding to brown-adipose-tissue mitochondria of young obese Zucker rats (fa/fa) was significantly lower than in lean control rats, as a result of a decrease in the number of binding sites. Adrenalectomy of fa/fa rats restored GDP binding to control values. Corticosterone replacement suppressed GDP binding in adrenalectomized obese rats.

scholarly journals Effects of Exercise Training on Brown Adipose Tissue Thermogenesis in Ovariectomized Obese Rats.

1989 ◽  
Vol 36 (3) ◽  
pp. 403-408 ◽  
Author(s):  
KEIJI YOSHIOKA ◽  
TOSHIHIDE YOSHIDA ◽  
YASUO WAKABAYASHI ◽  
HITOSHI NISHIOKA ◽  
MOTOHARU KONDO
Keyword(s):  
Adipose Tissue ◽  
Exercise Training ◽  
Brown Adipose Tissue ◽  
Brown Adipose ◽  
Obese Rats ◽  
Brown Adipose Tissue Thermogenesis

Rapid changes in number of GDP binding sites on brown adipose tissue mitochondria

1986 ◽  
Vol 251 (2) ◽  
pp. E192-E195
Author(s):  
A. G. Swick ◽  
R. W. Swick
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Binding Sites ◽  
Uncoupling Protein ◽  
Membrane Integrity ◽  
Binding Activity ◽  
Bat Mitochondria ◽  
Brown Adipose ◽  
Rapid Changes ◽  
Binding To Mitochondria

GDP binding to brown adipose tissue (BAT) mitochondria increased more than twofold in 20 min when rats were moved from 27 to 4 degrees C. When animals housed at 4 degrees C for 2 h were returned to 27 degrees C, GDP binding decreased sharply in 20 min and returned to control levels in 2 h. These results are consistent with a rapid unmasking and remasking of GDP binding sites. GDP binding to mitochondria from warm and acutely cold treated rats was not modified by prior swelling, by freeze-thawing, nor by sonication of the mitochondria before assay. GDP-inhibitable proton conductance, as measured by passive swelling, was unaffected by this brief exposure to cold but more than doubled in rats kept at 4 degrees C for 10 days. We hypothesize that the rate of GDP-inhibitable swelling may be a reflection of uncoupling protein concentration in the BAT mitochondria, whereas physiological thermogenic activity is more appropriately indicated by GDP binding. The alterations in binding activity appear not to be due to changes in the mitochondrial membrane integrity.

scholarly journals The β-adrenergic radioligand [3H]CGP-12177, generally classified as an antagonist, is a thermogenic agonist in brown adipose tissue

1989 ◽  
Vol 261 (2) ◽  
pp. 401-405 ◽  
Author(s):  
N Mohell ◽  
A Dicker
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Maximal Effect ◽  
Binding Studies ◽  
Isolated Cells ◽  
High Affinity ◽  
Brown Adipose ◽  
High Affinity Binding Site ◽  
Cgp 12177 ◽  
The One

The effect of CGP-12177, originally developed as a radioligand with antagonist properties for binding studies of beta-adrenergic receptors, was investigated in brown adipose tissue. Contrary to expectations, CGP-12177 showed clear agonist properties in experiments with hamster brown-fat cells, with a maximal effect in stimulating oxygen consumption similar to that of the physiological stimulator noradrenaline, and also with a potency similar to that of noradrenaline [EC50 (50% effective concn.) approx. 70 nM]. This value could be contrasted with the very high affinity of CGP-12177 (KD about 1 nM) for ligand-binding sites on the cells. It is therefore suggested that the high-affinity binding site may not be the one that mediates the CGP-12177-stimulated thermogenesis in isolated cells. Also, when injected into cold-adapted rats, CGP-12177 stimulated non-shivering thermogenesis similarly to noradrenaline. This observation, in conjunction with the reported low general sympathomimetic effect of CGP-12177, may indicate that CGP-12177 could be of interest for the development of anti-obesity drugs.

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