scholarly journals Brown-adipose-tissue mitochondria: the regulation of the 32 000-Mr uncoupling protein by fatty acids and purine nucleotides

1983 ◽  
Vol 137 (1-2) ◽  
pp. 197-203 ◽  
Author(s):  
Eduardo RIAL ◽  
Alison POUSTIE ◽  
David G. NICHOLLS
1998 ◽  
Vol 275 (2) ◽  
pp. C496-C504 ◽  
Author(s):  
Petr Jezek ◽  
Jirí Borecky

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.


2018 ◽  
Vol 120 (6) ◽  
pp. 619-627 ◽  
Author(s):  
Perla P. Argentato ◽  
Helena de Cássia César ◽  
Débora Estadella ◽  
Luciana P. Pisani

AbstractBrown adipose tissue (BAT) has recently been given more attention for the part it plays in obesity. BAT can generate great amounts of heat through thermogenesis by the activation of uncoupling protein 1 (UCP-1), which can be regulated by many environmental factors such as diet. Moreover, the build-up of BAT relates to maternal nutritional changes during pregnancy and lactation. However, at present, there is a limited number of studies looking at maternal nutrition and BAT development, and it seems that the research trend in this field has been considerably declining since the 1980s. There is much to discover yet about the role of different fatty acids on the development of BAT and the activation of UCP-1 during the fetal and the postnatal periods of life. A better understanding of the impact of nutritional intervention on the epigenetic regulation of BAT could lead to new preventive care for metabolic diseases such as obesity. It is important to know in which circumstances lipids could programme BAT during pregnancy and lactation. The modification of maternal dietary fatty acids, amount and composition, during pregnancy and lactation might be a promising strategy for the prevention of obesity in the offspring and future generations.


1984 ◽  
Vol 62 (7) ◽  
pp. 623-630 ◽  
Author(s):  
Ludwik J. Bukowiecki

The sequence of metabolic events leading to increased calorigenesis in brown adipose tissue has been reviewed. The first step of this sequence consists in the binding of norepinephrine to adrenergic receptors of the beta1 subtype. This results in the stimulation of adenylate cyclase and activation of lipolysis via the system of protein kinases. Hormone-sensitive lipases represent the "flux-generating" step regulating mitochondrial respiration. Fatty acids released from intracellular triglyceride droplets in consequence of lipase activation play a messenger role between lipolysis and mitochondrial respiration. They stimulate respiration by serving as substrates for beta oxidation (via carnitine-dependent pathways) and (or) by simultaneously increasing mitochondrial permeability to protons (physiological "loose coupling"). The control of brown adipose tissue respiration by lipolysis represents a self-regulatory process, as excessive concentrations of fatty acids retroinhibit lipolysis. At the mitochondrial level, fatty acids appear to interact with an "uncoupling" protein (thermogenin or 32 000 relative mass protein) localized in the inner membrane that confers upon brown adipose mitochondria a unique sensitivity for fatty acid uncoupling. This explains that, contrary to other tissues, respiration is principally controlled in brown adipose tissue by substrate supply (mainly long-chain fatty acids), rather than by the phosphorylation state ratio.


2011 ◽  
Vol 32 (1) ◽  
pp. 53-59 ◽  
Author(s):  
Leopoldo De Meis ◽  
Luisa A. Ketzer ◽  
Juliana Camacho-Pereira ◽  
Antonio Galina

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.


1995 ◽  
Vol 269 (2) ◽  
pp. E351-E360 ◽  
Author(s):  
A. Sadurskis ◽  
A. Dicker ◽  
B. Cannon ◽  
J. Nedergaard

To examine the effect of polyunsaturated fatty acids (PUFA) on brown adipose tissue recruitment and on the capacity for nonshivering thermogenesis (NST), mice were fed a diet with a standard fat content (9%) and a normal PUFA content (1.6%) (controls) or a high-PUFA content (4.3%) for 2-3 wk. The resting metabolic rate was somewhat lower in the high-PUFA group, probably due to a lower physical activity whereas the capacity for NST (estimated as the metabolic response to a norepinephrine injection) was higher in the high-PUFA group. There was no significant effect on brown adipose tissue wet weight, protein content, or cytochrome-c oxidase content, but the amount of the uncoupling protein thermogenin (UCP), measured immunologically, was significantly increased in the high-PUFA mice (totally by 41%). It was concluded that short-term feeding of a high-PUFA diet may recruit brown adipose tissue thermogenic capacity; it was speculated that earlier-reported recruiting effects of high-fat diets may not be due solely to the high total fat content of the diet but perhaps also to a specific recruiting property of the high-PUFA diets generally used in this type of investigation.


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