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.

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.

Brown adipose tissue in genetically obese (fa/fa) rats: response to cold and diet

1983 ◽  
Vol 244 (2) ◽  
pp. E145-E150 ◽  
Author(s):  
J. Triandafillou ◽  
J. Himms-Hagen
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cafeteria Diet ◽  
Chow Diet ◽  
Purine Nucleotides ◽  
Noradrenaline Content ◽  
Bat Mitochondria ◽  
Brown Adipose ◽  
Consequent Reduction ◽  
Diet Induced Thermogenesis

Young genetically obese (fatty, fa/fa) rats (7-8 wk old) maintained on a chow diet at 28 degrees C have a relatively normal amount of brown adipose tissue (BAT) (normal protein content, normal noradrenaline content, normal or slightly reduced cytochrome oxidase content, 30% reduction in DNA content) with cells grossly hypertrophied by accumulation of lipid. The binding of purine nucleotides by BAT mitochondria is lower in fa/fa rats than in lean rats, suggesting a lesser thermogenic activation of this tissue. Acute exposure to cold (24 h at 4 degrees C) activates BAT thermogenesis (visible hyperemia, marked increase in mitochondrial binding of purine nucleotides, depletion of noradrenaline content) in fa/fa rats as in lean rats. In contrast, feeding a cafeteria diet to young fa/fa rats fails to activate BAT (no increase in mitochondrial binding of purine nucleotides) as it does in lean rats, and these rats accumulate more extra fat (increase in weight of gonadal white adipose tissue) than do cafeteria diet-fed lean rats. It is concluded that the young fa/fa rat has normal cold-induced nonshivering thermogenesis in BAT but defective diet-induced thermogenesis in BAT and that the consequent reduction in energy expenditure, coupled with hyperphagia, contributes to the development of its obesity. The most probable location for the defect is suggested to be associated with the hypothalamus.

scholarly journals A Change in Liver Metabolism but Not in Brown Adipose Tissue Thermogenesis Is an Early Event in Ovariectomy-Induced Obesity in Rats

Endocrinology ◽  
2014 ◽  
Vol 155 (8) ◽  
pp. 2881-2891 ◽  
Author(s):  
Mariana Nigro ◽  
Anderson T. Santos ◽  
Clarissa S. Barthem ◽  
Ruy A. N. Louzada ◽  
Rodrigo S. Fortunato ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Brown Adipose Tissue ◽  
Glucose Homeostasis ◽  
Uncoupling Protein ◽  
Tolerance Test ◽  
Uncoupling Protein 1 ◽  
Ovx Rats ◽  
Bat Mitochondria ◽  
Brown Adipose

Menopause is associated with increased visceral adiposity and disrupted glucose homeostasis, but the underlying molecular mechanisms related to these metabolic changes are still elusive. Brown adipose tissue (BAT) plays a key role in energy expenditure that may be regulated by sexual steroids, and alterations in glucose homeostasis could precede increased weight gain after ovariectomy. Thus, the aim of this work was to evaluate the metabolic pathways in both the BAT and the liver that may be disrupted early after ovariectomy. Ovariectomized (OVX) rats had increased food efficiency as early as 12 days after ovariectomy, which could not be explained by differences in feces content. Analysis of isolated BAT mitochondria function revealed no differences in citrate synthase activity, uncoupling protein 1 expression, oxygen consumption, ATP synthesis, or heat production in OVX rats. The addition of GDP and BSA to inhibit uncoupling protein 1 decreased oxygen consumption in BAT mitochondria equally in both groups. Liver analysis revealed increased triglyceride content accompanied by decreased levels of phosphorylated AMP-activated protein kinase and phosphorylated acetyl-CoA carboxylase in OVX animals. The elevated expression of gluconeogenic enzymes in OVX and OVX + estradiol rats was not associated with alterations in glucose tolerance test or in serum insulin but was coincident with higher glucose disposal during the pyruvate tolerance test. Although estradiol treatment prevented the ovariectomy-induced increase in body weight and hepatic triglyceride and cholesterol accumulation, it was not able to prevent increased gluconeogenesis. In conclusion, the disrupted liver glucose homeostasis after ovariectomy is neither caused by estradiol deficiency nor is related to increased body mass.

scholarly journals Inflammation features of brown adipose tissue of rats with diet-induced obesity development after different regimes of melatonin administration

2021 ◽  
Vol 86 (3) ◽  
pp. 28-33
Author(s):  
O. Kalmukova ◽  
Y. Leonova ◽  
O. Savchuk ◽  
N. Skrypnyk ◽  
M. Dzerzhynsky
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Signal Pathways ◽  
Standard Diet ◽  
Low Grade ◽  
Leukocyte Infiltration ◽  
Diet Induced Obesity ◽  
Brown Adipose ◽  
Wide Range ◽  
Obese Rats

One of the prominent obesity-related changes is the development of systemic low-grade proinflammatory state. Brown adipose tissue (BAT) may serve as a potential target for activation by melatonin to facilitate heat production and simultaneously stimulate lipolysis during obesity development. At the same time, melatonin is known to have immunomodulatory properties, which are performed via endocrine and paracrine signal pathways in variety cell types (including brown adipocytes)and change significantly during the day. Therefore, it can be used in a wide range of doses and at different times of the day (chronotherapeutic approach). Thus, the main goal of our research was to analyze the inflammation state of brown adipose tissue of rats during high-calorie diet induced-obesity development after different daily melatonin application in different regimes. Melatonin was administered by gavage for 7 weeks in dose 30 mg/kg 1 h before lights-off (HCD ZT11, M ZT11, evening), or 1 h after lights-on (HCD ZT01, M ZT01, morning). Tissue collagen content and leukocyte infiltration levels in BAT, detected by Van Gieson trichrome staining, were used as markers for the assessment of BAT inflammation state BAT. Propagation of obesity resulted in the increase of BATfibrosis level (the relative area occupied by collagen fibers) and tissue leukocyte infiltration in comparison to control rats. BAT fibrosis level after melatonin administrations to obese rats of HCD ZT01 and HCD ZT11 groups decreased to control values. Similar effects were observedinBAT tissue leukocyte infiltration after both regimes (HCD ZT01 and HCD ZT11 groups) of melatonin intake: this parameter decreased significantly, comparing to obese rats, but was still elevated, comparing to controls. At the same time, melatonin treatmentin morning or evening regimes did not have any impact on BAT fibrosis propagation and leukocyte infiltration in animals that consumed standard diet (M ZT01 and M ZT11 groups). To sum up, we suggest corrective properties of melatonin in context of chronic low-grade inflammation in obese rats BAT and suppose its wide potential for the therapeutic use combined with virtually absent side effects on BAT histophysiology of non-obese rats.

scholarly journals Acute effects of a β-adrenoceptor agonist (BRL 26830A) on rat brown-adipose-tissue mitochondria. Increased GDP binding and GDP-sensitive proton conductance without changes in the concentration of uncoupling protein

1988 ◽  
Vol 249 (3) ◽  
pp. 759-763 ◽  
Author(s):  
R E Milner ◽  
S Wilson ◽  
J R Arch ◽  
P Trayhurn
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Binding Sites ◽  
Uncoupling Protein ◽  
Beta Agonist ◽  
Proton Conductance ◽  
Binding Data ◽  
Adrenoceptor Agonist ◽  
Brown Adipose ◽  
Acute Increase

GDP binding, proton conductance and the specific concentration of uncoupling protein were measured in brown-adipose-tissue mitochondria of rats treated acutely with the novel beta-agonist, BRL 26830A. At 1 h after dosing with BRL 26830A, mitochondrial GDP binding was increased more than 2-fold. The increase in binding resulted from an increase in the number of binding sites. An iterative analysis of Scatchard binding data suggested that there is only one high-affinity GDP-binding site (Kd 0.3 microM) in brown-adipose-tissue mitochondria. The acute increase in GDP binding produced by treatment with BRL 26830A occurred without any alteration in the specific mitochondrial concentration of uncoupling protein, as determined by radioimmunoassay. Treatment with the beta-agonist did, however, lead to a small increase in the GDP-sensitive component of mitochondrial proton conductance. These results indicate that GDP-binding sites on uncoupling protein can be rapidly unmasked after treatment with a brown-fat-specific beta-agonist, and that the increase in binding reflects an increase in the activity of the mitochondrial proton-conductance pathway.

Mitochondrial proton leak in brown adipose tissue mitochondria of Ucp1-deficient mice is GDP insensitive

1999 ◽  
Vol 276 (6) ◽  
pp. E1073-E1082 ◽  
Author(s):  
Shadi Monemdjou ◽  
Leslie P. Kozak ◽  
Mary-Ellen Harper
Keyword(s):  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Proton Leak ◽  
Control Analysis ◽  
Mitochondrial Uncoupling ◽  
Bat Mitochondria ◽  
Brown Adipose ◽  
Deficient Mice

Mice deficient in mitochondrial uncoupling protein (UCP) 1 are cold sensitive, despite abundant expression of the homologues, Ucp2 and Ucp3 (S. Enerbäck, A. Jacobsson, E. M. Simpson, C. Guerra, H. Yamashita, M.-E. Harper, and L. P. Kozak. Nature 387: 90–94, 1997). We have analyzed characteristics of mitochondrial proton leak from brown adipose tissue (BAT) of Ucp1-deficient mice and normal controls and conducted the first top-down metabolic control analysis of oxidative phosphorylation in BAT mitochondria. Because purine nucleotides inhibit UCP1 and because UCP2 and the long form of UCP3 have putative purine nucleotide-binding regions, we predicted that proton leak in BAT mitochondria from Ucp1-deficient mice would be sensitive to GDP. On the contrary, although control over mitochondrial oxygen consumption and proton leak reactions at state 4 are strongly affected by 1 mM GDP in mitochondria from normal mice, there is no effect in UCP1-deficient mitochondria. In the presence of GDP, the overall kinetics of proton leak were not significantly different between Ucp1-deficient mice and controls. In its absence, state 4 respiration in normal BAT mitochondria was double that in its presence. Leak-dependent oxygen consumption was higher over a range of membrane potentials in its absence than in its presence. Thus proton leak, potentially including that through UCP2 and UCP3, is GDP insensitive. However, our measurements were made in the presence of albumin and may not allow for the detection of any fatty acid-induced UCP-mediated leak; this possibility requires investigation.

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.

Changes in GDP binding to brown adipose tissue mitochondria and the uncoupling protein

1988 ◽  
Vol 255 (6) ◽  
pp. E865-E870
Author(s):  
A. G. Swick ◽  
R. W. Swick
Keyword(s):  
Alkaline Phosphatase ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Divalent Cations ◽  
Uncoupling Protein ◽  
Bat Mitochondria ◽  
Brown Adipose ◽  
Simplified Method

Incubation in vitro of brown adipose tissue (BAT) mitochondria with divalent cations, spermine, or alkaline phosphatase led to a marked increase in the binding of [3H]GDP. The effect of Mg2+ appeared to be the most specific and led to the largest increase in GDP binding. A simplified method was developed for measuring GDP binding to purified uncoupling protein from rat BAT mitochondria. Application of this method indicates that uncoupling protein from cold-acclimated rats binds twice as much GDP as uncoupling protein from cold-acclimated rats that were briefly returned to thermoneutrality, paralleling changes in GDP binding to the mitochondria. Incubation of BAT mitochondria with Mg2+ led to a smaller increase in GDP binding to the subsequently purified uncoupling protein, suggesting that divalent cations may somehow participate in the regulation of the activity of the uncoupling protein.

scholarly journals Brown adipose tissue mitochondria: modulation by GDP and fatty acids depends on the respiratory substrates

2011 ◽  
Vol 32 (1) ◽  
pp. 53-59 ◽  
Author(s):  
Leopoldo De Meis ◽  
Luisa A. Ketzer ◽  
Juliana Camacho-Pereira ◽  
Antonio Galina
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Membrane Potential ◽  
Brown Adipose Tissue ◽  
Heat Production ◽  
Uncoupling Protein ◽  
Atp Synthesis ◽  
Brown Adipocytes ◽  
Bat Mitochondria ◽  
Brown Adipose

The UCP1 [first UCP (uncoupling protein)] that is found in the mitochondria of brown adipocytes [BAT (brown adipose tissue)] regulates the heat production, a process linked to non-shivering thermogenesis. The activity of UCP1 is modulated by GDP and fatty acids. In this report, we demonstrate that respiration and heat released by BAT mitochondria vary depending on the respiratory substrate utilized and the coupling state of the mitochondria. It has already been established that, in the presence of pyruvate/malate, BAT mitochondria are coupled by faf-BSA (fatty-acid-free BSA) and GDP, leading to an increase in ATP synthesis and mitochondrial membrane potential along with simultaneous decreases in both the rates of respiration and heat production. Oleate restores the uncoupled state, inhibiting ATP synthesis and increasing the rates of both respiration and heat production. We now show that in the presence of succinate: (i) the rates of uncoupled mitochondria respiration and heat production are five times slower than in the presence of pyruvate/malate; (ii) faf-BSA and GDP accelerate heat and respiration as a result and, in coupled mitochondria, these two rates are accelerated compared with pyruvate/malate; (iii) in spite of the differences in respiration and heat production noted with the two substrates, the membrane potential and the ATP synthesized were the same; and (iv) oleate promoted a decrease in heat production and respiration in coupled mitochondria, an effect different from that observed using pyruvate/malate. These effects are not related to the production of ROS (reactive oxygen species). We suggest that succinate could stimulate a new route to heat production in BAT mitochondria.

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