Polypeptide turnover in brown adipose tissue mitochondria during acclimation of rats to cold

1980 ◽  
Vol 58 (4) ◽  
pp. 336-344 ◽  
Author(s):  
Jean Himms-Hagen ◽  
Elizabeth Dittmar ◽  
Gloria Zaror-Behrens

During the initial phase of cold-induced growth of brown adipose tissue in rats there is a selective increase in the incorporation of infused [3H]phenylalanine into mitochondrial membrane polypeptides of molecular weight 25 000–35 000. This is interpreted as a selective increase in the synthesis of a 32 000 polypeptide, of which the proportion is known to increase in brown adipose tissue mitochondria when the tissue has a high capacity for thermogenesis, as in the cold-acclimated rat. This polypeptide is known to be associated with the thermogenic proton conductance pathway. A simultaneous selective decrease in degradation or the formation from larger mitochondrial membrane polypeptides may also occur. In fully cold-acclimated rats, in which a new steady state is reached, there is a general increase in turnover of all mitochondrial membrane polypeptides but no marked selective changes in pattern of incorporation of radioactive amino acid or in rates of disappearance of radioactivity from groups of polypeptides. Isolated brown adipose tissue mitochondria incorporate [3H]phenylalanine principally into polypeptides of molecular weight 25 000–35 000. No change in the pattern of incorporation occurred in mitochondria isolated from brown adipose tissue of cold-exposed (2 weeks) rats. On the basis of these and preceding results it is concluded that the cold-induced change in mitochondrial composition in brown adipose tissue, which occurs at the same time as tissue and mitochondrial growth, is brought about by selective changes in cytosolic protein synthesis and possibly also by selectively altered degradation or conversion of mitochondrial polypeptides.

1982 ◽  
Vol 60 (8) ◽  
pp. 838-842 ◽  
Author(s):  
Mathias Fellenz ◽  
Joan Triandafillou ◽  
Cynthia Gwilliam ◽  
Jean Himms-Hagen

Brown adipose tissue (BAT) of rats is known to grow in response to acclimation to cold. The growth is accompanied by changes in mitochondrial polypeptide composition (an increase in the relative proportion of a polypeptide of molecular weight 32 000, known to be associated with the thermogenic proton conductance pathway). The mediator of the change in mitochondrial polypeptide composition is unknown. The objective of these experiments was to find out whether any of the pituitary hormones might be the mediator. Treatment of rats with growth hormone failed to alter BAT size or mitochondrial polypeptide composition. BAT grew and the change in BAT mitochondrial polypeptide composition occurred in cold-acclimated hypophysectomized rats, maintained on thyroxine and corticosterone to ensure their survival in the cold. It is concluded that none of the pituitary hormones is the mediator for the cold-induced change in BAT mitochondrial polypeptide composition or is required to exert a direct effect on BAT for cold-induced BAT growth to occur. It also seems unlikely that more than a maintenance amount of glucocorticoids is required for normal cold-induced growth of BAT; these hormones are thus also unlikely to mediate the change in BAT mitochondrial polypeptide composition. The requirement for no more than a maintenance amount of thyroxine for BAT growth and for the cold-induced change in BAT mitochondrial polypeptide composition confirms previous conclusions drawn from studies on cold-acclimated thyroidectomized rats.


1981 ◽  
Vol 241 (6) ◽  
pp. E436-E443
Author(s):  
S. Hogan ◽  
J. Himms-Hagen

Lean and genetically obese (ob/ob): mice were treated daily for 2 wk with thyroxine (T4), noradrenaline, or thyroxine plus noradrenaline. T4 treatment of obese mice increased the abnormally low binding of GDP to brown adipose tissue mitochondria and permitted a cold-induced increase to occur. It also brought about a return to a more normal ultrastructure of the mitochondria of the obese mice. T4 treatment did not alter the binding of GDP to brown adipose tissue mitochondria of lean mice. The binding of GDP to brown adipose tissue mitochondria is known to be to a 32,000-dalton polypeptide associated with the thermogenic proton conductance pathway. T4 treatment did not alter the proportion of this polypeptide in the mitochondrial membrane in either lean or obese mice. Treatment with noradrenaline did not alter the binding of GDP to brown adipose tissue mitochondria in either lean or obese mice. The effect of T4 is thought to be due to an improvement in the defective responsiveness of brown adipose tissue to endogenous noradrenaline in the obese mice, known to be related to their poor cold resistance and obesity. The improvement allows a more normal noradrenaline-induced unmasking of GDP binding sites, both in response to diet and in response to cold. Such treatment is known to improve cold resistance of the obese mice, and this appears to be correlated with an improvement in the functioning of their defective brown adipose tissue.


Cryobiology ◽  
1981 ◽  
Vol 18 (1) ◽  
pp. 106
Author(s):  
P. Svoboda ◽  
J. Houštěk ◽  
J. Kopecký ◽  
Z. Drahota

2007 ◽  
Vol 293 (5) ◽  
pp. R1773-R1780 ◽  
Author(s):  
Brian D. Fink ◽  
Judy A. Herlein ◽  
Katrine Almind ◽  
Saverio Cinti ◽  
C. Ronald Kahn ◽  
...  

We quantified uncoupling proteins (UCPs) in molar amounts and assessed proton conductance in mitochondria isolated from interscapular brown adipose tissue (IBAT) and hindlimb muscle [known from prior work to contain ectopic brown adipose tissue (BAT) interspersed between muscle fibers] of obesity-resistant 129S6/SvEvTac (129) and obesity-prone C57BL/6 (B6) mice under conditions of low (LF) and high-fat (HF) feeding. With usual feeding, IBAT mitochondrial UCP1 content and proton conductance were greater in 129 mice than B6. However, with HF feeding, UCP1 and proton conductance increased more in B6 mice. Moreover, with HF feeding GDP-inhibitable proton conductance, specific for UCP1, equaled that seen in the 129 strain. UCP1 expression was substantial in mitochondria from hindlimb muscle tissue (ectopic BAT) of 129 mice as opposed to B6 but did not increase with HF feeding in either strain. As expected, muscle UCP3 expression increased with HF feeding in both strains but did not differ by strain. Moreover, the proton conductance of mitochondria isolated from hindlimb muscle tissue did not differ by strain or diet. Our data uncover a response to weight gain in obesity-prone (compared to resistant) mice unrecognized in prior studies that examined only UCP1 mRNA. Obesity-prone mice have the capacity to increase both IBAT UCP1 protein and mitochondrial proton conductance as much or more than obesity-resistant mice. But, this is only achieved only at a higher body mass and, therefore, may be adaptive rather than preventative. Neither obesity-prone nor resistant mice respond to HF feeding by expressing more UCP1 in ectopic BAT within muscle tissue.


1988 ◽  
Vol 249 (3) ◽  
pp. 759-763 ◽  
Author(s):  
R E Milner ◽  
S Wilson ◽  
J R Arch ◽  
P Trayhurn

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.


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