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.

Hypothalamic obesity, brown adipose tissue, and sympathoadrenal activity in rats

1985 ◽  
Vol 248 (5) ◽  
pp. E607-E617 ◽  
Author(s):  
J. G. Vander Tuig ◽  
J. Kerner ◽  
D. R. Romsos
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Heat Production ◽  
Adult Rats ◽  
Guanosine Diphosphate ◽  
Bat Mitochondria ◽  
Sympathoadrenal Activity ◽  
Brown Adipose ◽  
Energy Retention ◽  
Ad Libitum

Obesity-producing, hypothalamic knife cuts and ventromedial hypothalamic (VMH) lesions in ad libitum-fed adult rats increased intake of a high-fat diet (123 and 130%) and energy retention (880 and 1,099%) during the 4-wk period postsurgery; even when pair fed to control rats, energy retention of the knife-cut and lesioned rats was still elevated (105 and 155%). Thermogenic capacity of brown adipose tissue (BAT), estimated from guanosine diphosphate (GDP) binding to BAT mitochondria, was unchanged in hyperphagic knife-cut and VMH-lesioned rats and was reduced approximately 50% when these rats were pair fed to controls. Urinary excretion of norepinephrine (NE) was approximately twofold higher in ad libitum-fed, knife-cut, and lesioned rats than in control rats; restriction of energy intake decreased NE excretion to control values. Rates of NE turnover in heart paralleled urinary NE excretion, whereas NE turnover in BAT was generally not increased in the hyperphagic rats. Urinary epinephrine excretion, an index of adrenal medullary activity, was depressed in all knife-cut and VMH-lesioned rats. Hyperphagia coupled with a lack of increased heat production in BAT causes gross obesity in ad libitum-fed, knife-cut, and VMH-lesioned rats, whereas obesity in pair-fed rats develops in part at least as a result of reduced heat production by BAT.

Brown Adipose Tissue: Function and Physiological Significance

2004 ◽  
Vol 84 (1) ◽  
pp. 277-359 ◽  
Author(s):  
BARBARA CANNON ◽  
JAN NEDERGAARD
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Heat Production ◽  
Uncoupling Protein ◽  
Sympathetic Nerves ◽  
Physiological Significance ◽  
Metabolic Efficiency ◽  
Transfer Energy ◽  
Brown Adipose ◽  
Evolutionary Success

Cannon, Barbara, and Jan Nedergaard. Brown Adipose Tissue: Function and Physiological Significance. Physiol Rev 84: 277–359, 2004; 10.1152/physrev.00015.2003.—The function of brown adipose tissue is to transfer energy from food into heat; physiologically, both the heat produced and the resulting decrease in metabolic efficiency can be of significance. Both the acute activity of the tissue, i.e., the heat production, and the recruitment process in the tissue (that results in a higher thermogenic capacity) are under the control of norepinephrine released from sympathetic nerves. In thermoregulatory thermogenesis, brown adipose tissue is essential for classical nonshivering thermogen-esis (this phenomenon does not exist in the absence of functional brown adipose tissue), as well as for the cold acclimation-recruited norepinephrine-induced thermogenesis. Heat production from brown adipose tissue is activated whenever the organism is in need of extra heat, e.g., postnatally, during entry into a febrile state, and during arousal from hibernation, and the rate of thermogenesis is centrally controlled via a pathway initiated in the hypothalamus. Feeding as such also results in activation of brown adipose tissue; a series of diets, apparently all characterized by being low in protein, result in a leptin-dependent recruitment of the tissue; this metaboloregulatory thermogenesis is also under hypothalamic control. When the tissue is active, high amounts of lipids and glucose are combusted in the tissue. The development of brown adipose tissue with its characteristic protein, uncoupling protein-1 (UCP1), was probably determinative for the evolutionary success of mammals, as its thermogenesis enhances neonatal survival and allows for active life even in cold surroundings.

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 Mitochondrial uncoupling protein may participate in futile cycling of pyruvate and other monocarboxylates

1998 ◽  
Vol 275 (2) ◽  
pp. C496-C504 ◽  
Author(s):  
Petr Jezek ◽  
Jirí Borecky
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Specific Inhibitor ◽  
Physiological Role ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
Brown Adipose ◽  
Futile Cycling

The physiological role of monocarboxylate transport in brown adipose tissue mitochondria has been reevaluated. We studied pyruvate, α-ketoisovalerate, α-ketoisocaproate, and phenylpyruvate uniport via the uncoupling protein (UCP1) as a GDP-sensitive swelling in K+ salts induced by valinomycin or by monensin and carbonyl cyanide- p-(trifluoromethoxy)phenylhydrazone in Na+ salts. We have demonstrated that this uniport is inhibited by fatty acids. GDP inhibition in K+ salts was not abolished by an uncoupler, indicating a negligible monocarboxylic acid penetration via the lipid bilayer. In contrast, the electroneutral pyruvate uptake (swelling in ammonium pyruvate or potassium pyruvate induced by change in pH) mediated by the pyruvate carrier was inhibited by its specific inhibitor α-cyano-4-hydroxycinnamate but not by fatty acids. Moreover, α-cyano-4-hydroxycinnamate enhanced the energization of brown adipose tissue mitochondria, which was monitored fluorometrically by 2-(4-dimethylaminostyryl)-1-methylpyridinium iodide and safranin O. Consequently, we suggest that UCP1 might participate in futile cycling of unipolar ketocarboxylates under certain physiological conditions while expelling these anions from the matrix. The cycle is completed on their return via the pyruvate carrier in an H+ symport mode.

Uncoupling protein 1 expression and high-fat diets

2011 ◽  
Vol 300 (1) ◽  
pp. R1-R8 ◽  
Author(s):  
Tobias Fromme ◽  
Martin Klingenspor
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Caloric Intake ◽  
High Fat ◽  
Uncoupling Protein 1 ◽  
Brown Adipocytes ◽  
Adaptive Thermogenesis ◽  
Brown Adipose ◽  
Thermoregulatory Function

Uncoupling protein 1 (Ucp1) is the key component of β-adrenergically controlled nonshivering thermogenesis in brown adipocytes. This process combusts stored and nutrient energy as heat. Cold exposure not only activates Ucp1-mediated thermogenesis to maintain normothermia but also results in adaptive thermogenesis, i.e., the recruitment of thermogenic capacity in brown adipose tissue. As a hallmark of adaptive thermogenesis, Ucp1 synthesis is increased proportionally to temperature and duration of exposure. Beyond this classical thermoregulatory function, it has been suggested that Ucp1-mediated thermogenesis can also be employed for metabolic thermogenesis to prevent the development of obesity. Accordingly, in times of excess caloric intake, one may expect a positive regulation of Ucp1. The general impression from an overview of the present literature is, indeed, an increased brown adipose tissue Ucp1 mRNA and protein content after feeding a high-fat diet (HFD) to mice and rats. The reported increases are very variable in magnitude, and the effect size seems to be independent of dietary fat content and duration of the feeding trial. In white adipose tissue depots Ucp1 mRNA is generally downregulated by HFD, indicating a decline in the number of interspersed brown adipocytes.

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.

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