scholarly journals Chemical modification of the brown fat mitochondrial uncoupling protein with tetranitromethane

FEBS Letters ◽  
1986 ◽  
Vol 198 (1) ◽  
pp. 29-32 ◽  
Author(s):  
Eduardo Rial ◽  
David G. Nicholls
1991 ◽  
Vol 11 (8) ◽  
pp. 4147-4156 ◽  
Author(s):  
B B Boyer ◽  
L P Kozak

The mitochondrial uncoupling protein gene is rapidly induced in mouse brown fat following cold exposure. To identify cis-regulatory elements, approximately 50 kb of chromatin surrounding the uncoupling protein gene was examined for its hypersensitivity to DNase I. Seven DNase I-hypersensitive sites were identified in the 5'-flanking DNA, and one site was identified in the 3'-flanking DNA. Transgenic mice with an uncoupling protein minigene were generated by microinjection of fertilized eggs with a transgene containing 3 kb of 5'-flanking DNA and 0.3 kb of 3'-flanking DNA. Expression of the transgene is restricted to brown fat and is cold inducible. Four additional transgenic lines were generated with a second transgene containing a 1.8-kb deletion in the 5'-flanking DNA, and expression of this minigene is absent in all tissues analyzed. A DNase I-hypersensitive site located in the 1.8-kb deletion contains a cyclic AMP response element that binds a brown fat tumor enriched nuclear factor. On the basis of these observations, we propose that a cis-acting regulatory sequence between -3 and -1.2 kb of the 5'-flanking region, possibly at a DNase I-hypersensitive site, is required for controlling uncoupling protein expression in vivo.


1990 ◽  
Vol 68 (8) ◽  
pp. 1100-1107 ◽  
Author(s):  
M. Desautels ◽  
R. A. Dulos

In euthyroid mice, a 48-h fast caused brown fat (BAT) atrophy characterized by loss of tissue proteins, succinate dehydrogenase (SDH), and a significant reduction in mitochondrial uncoupling protein (UCP) content. Chemical sympathectomy and surgical denervation failed to mimic the changes in BAT protein and SDH contents observed after food deprivation. However, suppression of sympathetic activity could account for the loss of UCP from the mitochondria. In mice made hyperthyroid by repeated triiodothyronine injections, losses of tissue SDH and proteins caused by food deprivation or surgical denervation were markedly suppressed, while the loss of UCP from the mitochondria remained unchanged. These results suggest that reduced sympathetic activity to BAT in fasted mice is not the exclusive cause of the tissue atrophy and that thyroid hormones may play a role in the control of brown fat atrophy in mice.Key words: brown adipose tissue, thermogenesis, uncoupling protein, energy balance, body weight, sympathetic nervous system.


1991 ◽  
Vol 260 (6) ◽  
pp. R1229-R1234 ◽  
Author(s):  
P. Soppela ◽  
M. Nieminen ◽  
S. Saarela ◽  
J. S. Keith ◽  
J. N. Morrison ◽  
...  

Reindeer inhabit a severe arctic or subarctic environment, with the young born in early spring under adverse weather conditions. The extreme northern climate imposes a major thermal challenge to the newborn, and in the present study we have examined fetal, neonatal, and young (from 2 wk before birth to 16 mo postpartum) semidomesticated reindeer from northern Finland for the presence of thermogenic brown adipose tissue. Adipose tissues were removed, mitochondria were prepared, and the proteins were separated by molecular weight and blotted onto nitrocellulose membranes. The membranes were then probed for the presence of the 32,000-relative molecular weight mitochondrial uncoupling protein (UCP) unique to brown fat by use of a rabbit anti-(ground squirrel UCP) serum. Immunoreactivity at the molecular weight characteristic of UCP was present in perirenal, abdominal, inter(pre)scapular, sternal, intralumbar, vertebral, tracheal, inguinal, and omental-mesenteral adipose tissues of newborn reindeer (0-2 days of age). No immunoreactivity was detected in coronary adipose tissue. UCP was found at high levels in interscapular and perirenal adipose tissues of fetal reindeer at 2 wk before birth. Although the protein was present during the first few days postpartum, little immunoreactivity was found at 1 mo of age, and none was evident by 2 mo. UCP and its mRNA were also apparent in perirenal adipose tissue of the newborn of another species of Cervidae, the red deer. It is concluded, on the basis of the immunologic identification of UCP, that most adipose tissues of newborn reindeer represent functional brown fat but that there is a subsequent conversion to white adipose tissue by the 2nd mo of life.(ABSTRACT TRUNCATED AT 250 WORDS)


2006 ◽  
Vol 290 (5) ◽  
pp. E1014-E1021 ◽  
Author(s):  
Ken-ichi Inokuma ◽  
Yuko Okamatsu-Ogura ◽  
Asako Omachi ◽  
Yukiko Matsushita ◽  
Kazuhiro Kimura ◽  
...  

Mitochondrial uncoupling protein-1 (UCP1) has been thought to be a key molecule for thermogenesis during cold exposure and spontaneous hyperphagia and thereby in the autonomic regulation of energy expenditure and adiposity. However, UCP1 knockout (KO) mice were reported to be cold intolerant but unexpectedly did not get obese even after hyperphagia, implying that UCP1 may not be involved in the regulation of adiposity. Treatment of obese animals with β3-adrenergic agonists is known to increase lipid mobilization, induce UCP1, and, finally, reduce body fat content. To obtain direct evidence for the role of UCP1 in the anti-obesity effect of β3-adrenergic stimulation, in the present study, UCP1-KO and wild-type (WT) mice were fed on cafeteria diets for 8 wk and then given a β3-adrenergic agonist, CL-316,243 (CL), or saline for 2 wk. A single injection of CL increased whole body oxygen consumption and brown fat temperature in WT mice but not in KO mice, and it elicited almost the same plasma free fatty acid response in WT and KO mice. WT and KO mice increased similarly their body and white fat pad weights on cafeteria diets compared with those on laboratory chow. Daily treatment with CL resulted in a marked reduction of white fat pad weight and the size of adipocytes in WT mice, but not in KO mice. Compared with WT mice, KO mice expressed increased levels of UCP2 in brown fat but decreased levels in white fat and comparable levels of UCP3. It was concluded that the anti-obesity effect of β3-adrenergic stimulation is largely attributable to UCP1, but less to UCP2 and UCP3, and thereby to UCP1-dependent degradation of fatty acids released from white adipose tissue.


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