scholarly journals Mechanism of Fatty-Acid-Dependent UCP1 Uncoupling in Brown Fat Mitochondria

Cell ◽  
2012 ◽  
Vol 151 (2) ◽  
pp. 400-413 ◽  
Author(s):  
Andriy Fedorenko ◽  
Polina V. Lishko ◽  
Yuriy Kirichok
Keyword(s):  
Fatty Acid ◽  
Brown Fat ◽  
Brown Fat Mitochondria

scholarly journals Effects of Genetic Background on Thermoregulation and Fatty Acid-induced Uncoupling of Mitochondria in UCP1-deficient Mice

2001 ◽  
Vol 276 (15) ◽  
pp. 12460-12465 ◽  
Author(s):  
Wolfgang E. Hofmann ◽  
Xiaotuan Liu ◽  
Christie M. Bearden ◽  
Mary-Ellen Harper ◽  
Leslie P. Kozak
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acids ◽  
Genetic Background ◽  
Brown Fat ◽  
Cold Sensitivity ◽  
F1 Hybrid ◽  
And Control ◽  
Brown Fat Mitochondria ◽  
Deficient Mice

An interaction between free fatty acids and UCP1 (uncouplingprotein-1) leading to de-energization of mitochondria was assumed to be a key event for triggering heat production in brown fat. Recently, Matthiaset al., finding indistinguishable de-energization of isolated brown fat mitochondria by fatty acids in UCP1-deficient mice and control mice, challenged this assumption (Matthias, A., Jacobsson, A., Cannon, B., and Nedergaard, J. (1999)J. Biol. Chem.274, 28150–28160). Since their results were obtained using UCP1-deficient and control mice on an undefined genetic background, we wanted to determine unambiguously the phenotype of UCP1 deficiency with the targetedUcp1allele on congenic C57BL/6J and 129/SvImJ backgrounds. UCP1-deficient congenic mice have a very pronounced cold-sensitive phenotype; however, deficient mice on the F1 hybrid background were resistant to cold. We propose that heterosis provides a mechanism to compensate for UCP1 deficiency. Contrary to the results of Matthiaset al., we found a significant loss of fatty acid-induced de-energization, as reflected by membrane potential and oxygen consumption, in brown fat mitochondria from UCP1-deficient mice. Unlike cold sensitivity, fatty acid-induced uncoupling of mitochondria was independent of the genetic background of UCP1-deficient mice. We propose that intracellular free fatty acids directly regulate uncoupling activity of UCP1 in a manner consistent with models described in the literature.

Barbara Cannon's Data on the UCP1-Ablated Mice: “Non-Cannonical” Point of View

2001 ◽  
Vol 21 (2) ◽  
pp. 189-194 ◽  
Author(s):  
Vladimir P. Skulachev
Keyword(s):  
Fatty Acid ◽  
Resting State ◽  
Proton Motive Force ◽  
Point Of View ◽  
Brown Fat ◽  
Strong Decrease ◽  
Normal Body Temperature ◽  
Brown Fat Mitochondria ◽  
Term Maintenance

The data of Cannon and co-workers on UCP1-ablated mice are interpreted assuming that UCP2 and UCP3 are involved in thermoregulation as fatty acid-dependent uncouplers although they are not sufficient, in the absence of UCP1, for long term maintenance of normal body temperature of mice after sudden and strong decrease in the ambient temperature. I would like to suggest that in brown fat of control mice, UCP1 is present in an amount higher than UCP2 and 3 and, therefore, is able to cause (a) some fatty acid-mediated decrease in proton motive force in resting state and, hence, (b) oxidation of CoQH2 to CoQ which is shown by Klingenberg and coworkers to be cofactor for UCPs. This results in strong uncoupling and thermogenesis mediated by UCP1, 2 and 3. In the UCP1-ablated mice, activity of UCP2 and 3 appears to be insufficient to induce CoQH2 oxidation in resting brown fat mitochondria, which results in hypothermia.

scholarly journals Carboxyatractyloside effects on brown-fat mitochondria imply that the adenine nucleotide translocator isoforms ANT1 and ANT2 may be responsible for basal and fatty-acid-induced uncoupling respectively

2006 ◽  
Vol 399 (3) ◽  
pp. 405-414 ◽  
Author(s):  
Irina G. Shabalina ◽  
Tatiana V. Kramarova ◽  
Jan Nedergaard ◽  
Barbara Cannon
Keyword(s):  
Fatty Acid ◽  
Adenine Nucleotide ◽  
Liver Mitochondria ◽  
Basal Respiration ◽  
Brown Fat ◽  
Proton Leak ◽  
Mrna Levels ◽  
Adenine Nucleotide Translocator ◽  
Brown Adipose ◽  
Brown Fat Mitochondria

In brown-fat mitochondria, fatty acids induce thermogenic uncoupling through activation of UCP1 (uncoupling protein 1). However, even in brown-fat mitochondria from UCP1−/− mice, fatty-acid-induced uncoupling exists. In the present investigation, we used the inhibitor CAtr (carboxyatractyloside) to examine the involvement of the ANT (adenine nucleotide translocator) in the mediation of this UCP1-independent fatty-acid-induced uncoupling in brown-fat mitochondria. We found that the contribution of ANT to fatty-acid-induced uncoupling in UCP1−/− brown-fat mitochondria was minimal (whereas it was responsible for nearly half the fatty-acid-induced uncoupling in liver mitochondria). As compared with liver mitochondria, brown-fat mitochondria exhibit a relatively high (UCP1-independent) basal respiration (‘proton leak’). Unexpectedly, a large fraction of this high basal respiration was sensitive to CAtr, whereas in liver mitochondria, basal respiration was CAtr-insensitive. Total ANT protein levels were similar in brown-fat mitochondria from wild-type mice and in liver mitochondria, but the level was increased in brown-fat mitochondria from UCP1−/− mice. However, in liver, only Ant2 mRNA was found, whereas in brown adipose tissue, Ant1 and Ant2 mRNA levels were equal. The data are therefore compatible with a tentative model in which the ANT2 isoform mediates fatty-acid-induced uncoupling, whereas the ANT1 isoform may mediate a significant part of the high basal proton leak in brown-fat mitochondria.

Brown fat mitochondria

1984 ◽  
Vol 9 (11) ◽  
pp. 489-491 ◽  
Author(s):  
David G. Nicholls ◽  
Eduardo Rial
Keyword(s):  
Brown Fat ◽  
Brown Fat Mitochondria

GDP binding to rat brown fat mitochondria: effects of thyroxine at different ambient temperatures

1981 ◽  
Vol 241 (3) ◽  
pp. C134-C139 ◽  
Author(s):  
U. Sundin
Keyword(s):  
Linear Increase ◽  
Reciprocal Relationship ◽  
Brown Fat ◽  
Hormone Activity ◽  
Ambient Temperatures ◽  
Heating Capacity ◽  
Brown Adipose ◽  
Induced Changes ◽  
Brown Fat Mitochondria

Reports on a reciprocal relationship between sympathetic-nerve and experimentally induced changes in thyroid-hormone activity called into question the proposed role of thyroxine in the changes seen in the brown fat after cold adaptation. Rats reared at +30, +22, and +5 degrees C received daily injections of thyroxine (1 mg/kg). After 3 wk of treatment, the thermogenic state of the tissue was assessed by measuring the capacity of the brown fat mitochondria to bind guanosine 5'-diphosphate (GDP). GDP-inhibited mitochondrial swelling, brown adipose tissue (BAT) wet weights, and mitochondrial yields were also measured. The control animals showed a linear increase in GDP binding between +30 and +5 degrees C. Thyroxine was found to lower the GDP binding markedly at +5 degrees C, less so at +22 degrees C, while no effect was evident at +30 degrees C. The values at +22 and +30 degrees C were identical. The other parameters studied all confirmed these results. The conclusion made is that the thyroxine-induced rise in basal metabolic rate lowers the critical temperature and reduces the demand for nonshivering thermogenesis. This is reflected in the reduced GDP binding and hence heating capacity of the brown fat mitochondria.

Effect of noradrenaline chronic administration on brown fat phospholipids

1988 ◽  
Vol 8 (5) ◽  
pp. 465-469 ◽  
Author(s):  
Gérard Mory ◽  
Myriam Gawer ◽  
Jean-Claude Kader
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Brown Adipose Tissue ◽  
Acid Composition ◽  
Cold Exposure ◽  
Chronic Administration ◽  
Sympathetic Tone ◽  
Brown Fat ◽  
Brown Adipose

Chronic cold exposure of rats (9 days at 5°C) induces an alteration of the fatty acid composition of phospholipids in brown adipose tissue. The alteration is due to an increase of the unsaturation degree of these lipids. The phenomenon can be reproduced by 10−7 mole. h−1 administration of noradrenaline for 9 days in rats kept at 25°C. Thus, phospholipid alteration in brown fat of cold exposed rats is most probably a consequence of the increase of sympathetic tone which occurs in this tissue during exposure to cold.

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