Mechanisms of stimulus-calorigenesis coupling in brown adipose tissue

1984 ◽  
Vol 62 (7) ◽  
pp. 623-630 ◽  
Author(s):  
Ludwik J. Bukowiecki
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Mitochondrial Respiration ◽  
Uncoupling Protein ◽  
Relative Mass ◽  
Tissue Respiration ◽  
Beta Oxidation ◽  
Brown Adipose ◽  
Hormone Sensitive

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.

Insulin selectively reduces mitochondrial uncoupling in brown adipose tissue in mice

2018 ◽  
Vol 475 (3) ◽  
pp. 561-569 ◽  
Author(s):  
Blake W. Dallon ◽  
Brian A. Parker ◽  
Aimee E. Hodson ◽  
Trevor S. Tippetts ◽  
Mitchell E. Harrison ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Mitochondrial Respiration ◽  
Insulin Treatment ◽  
Uncoupling Protein ◽  
Mitochondrial Uncoupling ◽  
Adipose Tissue Depots ◽  
Brown Adipose ◽  
A Site

The purpose of the present study was to determine the effects of prolonged hyperinsulinemia on mitochondrial respiration and uncoupling in distinct adipose tissue depots. Sixteen-week-old male mice were injected daily with placebo or insulin to induce an artificial hyperinsulinemia for 28 days. Following the treatment period, mitochondrial respiration and degree of uncoupling were determined in permeabilized perirenal, inguinal, and interscapular adipose tissue. White adipose tissue (WAT) mitochondria (inguinal and perirenal) respire at substantially lower rates compared with brown adipose tissue (BAT). Insulin treatment resulted in a significant reduction in mitochondrial respiration in inguinal WAT (iWAT) and interscapular BAT (iBAT), but not in perirenal WAT (pWAT). Furthermore, these changes were accompanied by an insulin-induced reduction in UCP-1 (uncoupling protein 1) and PGC-1α in iWAT and iBAT only, but not in pWAT or skeletal muscle. Compared with adipose tissue mitochondria in placebo conditions, adipose tissue from hyperinsulinemic mice manifested a site-specific reduction in mitochondrial respiration probably as a result of reduced uncoupling. These results may help explain weight gain so commonly seen with insulin treatment in type 2 diabetes mellitus.

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.

scholarly journals Reversible temperature-dependent differences in brown adipose tissue respiration during torpor in a mammalian hibernator

2017 ◽  
Vol 312 (3) ◽  
pp. R434-R442 ◽  
Author(s):  
Sarah V. McFarlane ◽  
Katherine E. Mathers ◽  
James F. Staples
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Mitochondrial Respiration ◽  
Enzyme Activities ◽  
Energy Savings ◽  
Tissue Respiration ◽  
Membrane Phospholipids ◽  
Respiration Rates ◽  
Bat Mitochondria ◽  
Brown Adipose

Although seasonal modifications of brown adipose tissue (BAT) in hibernators are well documented, we know little about functional regulation of BAT in different phases of hibernation. In the 13-lined ground squirrel, liver mitochondrial respiration is suppressed by up to 70% during torpor. This suppression is reversed during arousal and interbout euthermia (IBE), and corresponds with patterns of maximal activities of electron transport system (ETS) enzymes. Uncoupling of BAT mitochondria is controlled by free fatty acid release stimulated by sympathetic activation of adipocytes, so we hypothesized that further regulation at the level of the ETS would be of little advantage. As predicted, maximal ETS enzyme activities of isolated BAT mitochondria did not differ between torpor and IBE. In contrast to this pattern, respiration rates of mitochondria isolated from torpid individuals were suppressed by ~60% compared with rates from IBE individuals when measured at 37°C. At 10°C, however, mitochondrial respiration rates tended to be greater in torpor than IBE. As a result, the temperature sensitivity (Q10) of mitochondrial respiration was significantly lower in torpor (~1.4) than IBE (~2.4), perhaps facilitating energy savings during entrance into torpor and thermogenesis at low body temperatures. Despite the observed differences in isolated mitochondria, norepinephrine-stimulated respiration rates of isolated BAT adipocytes did not differ between torpor and IBE, perhaps because the adipocyte isolation requires lengthy incubation at 37°C, potentially reversing any changes that occur in torpor. Such changes may include remodeling of BAT mitochondrial membrane phospholipids, which could change in situ enzyme activities and temperature sensitivities.

scholarly journals Programming mediated by fatty acids affects uncoupling protein 1 (UCP-1) in brown adipose tissue

2018 ◽  
Vol 120 (6) ◽  
pp. 619-627 ◽  
Author(s):  
Perla P. Argentato ◽  
Helena de Cássia César ◽  
Débora Estadella ◽  
Luciana P. Pisani
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Dietary Fatty Acids ◽  
Research Trend ◽  
Uncoupling Protein 1 ◽  
Brown Adipose ◽  
Pregnancy And Lactation ◽  
The Impact

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.

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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