Cold-induced alterations in uncoupling protein and its mRNA are seasonally dependent in ground squirrels

1995 ◽  
Vol 269 (2) ◽  
pp. R357-R364
Author(s):  
S. E. Nizielski ◽  
C. J. Billington ◽  
A. S. Levine
Keyword(s):  
Cold Exposure ◽  
Uncoupling Protein ◽  
Late Summer ◽  
Ground Squirrels ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
Beta Actin ◽  
Mrna Ratio ◽  
Brown Adipose ◽  
Actin Mrna

We were interested in determining whether season affects the ability of cold exposure to increase brown adipose tissue (BAT) thermogenic function in 13-lined ground squirrels after acute and chronic cold (4 degrees C) exposure. Tissues were collected from animals in April and September after cold exposure for 12, 24, or 48 h. Animals chronically exposed to the cold (10 days) were killed in early May and mid-August. We found that mitochondrial uncoupling protein (UCP) concentrations varied seasonally, with concentrations in control animals (at 23 degrees C) higher in late summer (mid-August and September) than in the spring (April and early May). Cold exposure in late summer did not induce further increases in UCP concentrations. In contrast, when animals were cold exposed in the spring, UCP concentrations and total UCP increased. Surprisingly, 10 days at 4 degrees C did not cause a greater increase in UCP concentrations than did 24 h at 4 degrees C. Chronic cold exposure increased the UCP mRNA-to-beta-actin mRNA ratio 48% in May, whereas a fivefold increase occurred in August. GDP binding was increased after 12 h at 4 degrees C in April; in contrast, animals attempted to hibernate when placed in the cold in September, and no increase in GDP binding was observed. Chronic cold exposure caused GDP binding to increase at both times. These results indicate that mitochondrial UCP concentrations are seasonally regulated in the 13-lined ground squirrel.

BAT thermogenic activity and capacity are reduced during lactation in ground squirrels

1993 ◽  
Vol 264 (1) ◽  
pp. R16-R21 ◽  
Author(s):  
S. E. Nizielski ◽  
C. J. Billington ◽  
A. S. Levine
Keyword(s):  
Gene Expression ◽  
Ground Squirrel ◽  
Specific Binding ◽  
Uncoupling Protein ◽  
Ground Squirrels ◽  
Scatchard Analysis ◽  
Mitochondrial Mass ◽  
Beta Actin ◽  
Brown Adipose ◽  
Actin Mrna

The effect of lactation on brown adipose tissue (BAT) thermogenic activity and capacity as well as on uncoupling protein (UCP) gene expression has been studied in the 13-lined ground squirrel. Lactating animals were studied after approximately 21 days of lactation. Parameters of thermogenesis were also studied in a group of postpregnant animals from which litters had been removed at 1-2 days postpartum. A group of animals that did not bear litters served as nonpregnant controls. BAT pad weights, protein concentration, and mitochondrial mass were all significantly decreased relative to nonpregnant controls and postpregnant animals. Specific binding of GDP and total GDP bound were significantly decreased in lactating animals relative to both nonpregnant and postpregnant animals. Scatchard analysis of GDP binding indicated that binding affinity (Kd) was unaffected by treatment. UCP concentrations were reduced by 26% during lactation, whereas total UCP content was reduced by 70%. A 3-wk period after pup removal was sufficient for UCP concentrations to return to nonpregnant levels, although total UCP content remained reduced. The changes in UCP concentrations were accompanied by parallel alterations of gene expression. UCP mRNA-to-beta-actin mRNA ratios during lactation were 30% of the levels found in nonpregnant controls and postpregnant animals. The results presented here clearly indicate that BAT activity and capacity are suppressed during lactation in the 13-lined ground squirrel.

Differential regulation of uncoupling protein gene homologues in multiple tissues of hibernating ground squirrels

1998 ◽  
Vol 275 (4) ◽  
pp. R1232-R1238 ◽  
Author(s):  
Bert B. Boyer ◽  
Brian M. Barnes ◽  
Bradford B. Lowell ◽  
Danica Grujic
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Uncoupling Protein ◽  
Ground Squirrels ◽  
Mrna Levels ◽  
Parallel Mechanisms ◽  
Mitochondrial Uncoupling ◽  
Spermophilus Parryii ◽  
Mitochondrial Uncoupling Protein ◽  
Brown Adipose

Nonshivering thermogenesis in brown adipose tissue (BAT) provides heat through activation of a mitochondrial uncoupling protein (UCP1), which causes futile electron transport cycles without the production of ATP. Recent discovery of two molecular homologues, UCP2, expressed in multiple tissues, and UCP3, expressed in muscle, has resulted in investigation of their roles in thermoregulatory physiology and energy balance. To determine the expression pattern of Ucp homologues in hibernating mammals, we compared relative mRNA levels of Ucp1, -2, and -3 in BAT, white adipose tissue (WAT), and skeletal muscle of arctic ground squirrels ( Spermophilus parryii) hibernating at different ambient and body temperatures, with levels determined in tissues from ground squirrels not in hibernation. Here we report significant increases in mRNA levels for Ucp2 in WAT (1.6-fold) and Ucp3 in skeletal muscle (3-fold) during hibernation. These results indicate the potential for a role of UCP2 and UCP3 in thermal homeostasis during hibernation and indicate that parallel mechanisms and multiple tissues could be important for nonshivering thermoregulation in mammals.

scholarly journals Neuronal UCP1 expression suggests a mechanism for local thermogenesis during hibernation

2015 ◽  
Vol 112 (5) ◽  
pp. 1607-1612 ◽  
Author(s):  
Willem J. Laursen ◽  
Marco Mastrotto ◽  
Dominik Pesta ◽  
Owen H. Funk ◽  
Jena B. Goodman ◽  
...  
Keyword(s):  
Body Temperature ◽  
Molecular Mechanisms ◽  
Brain Temperature ◽  
Uncoupling Protein ◽  
Ground Squirrels ◽  
The Body ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
Brown Adipose

Hibernating mammals possess a unique ability to reduce their body temperature to ambient levels, which can be as low as −2.9 °C, by active down-regulation of metabolism. Despite such a depressed physiologic phenotype, hibernators still maintain activity in their nervous systems, as evidenced by their continued sensitivity to auditory, tactile, and thermal stimulation. The molecular mechanisms that underlie this adaptation remain unknown. We report, using differential transcriptomics alongside immunohistologic and biochemical analyses, that neurons from thirteen-lined ground squirrels (Ictidomys tridecemlineatus) express mitochondrial uncoupling protein 1 (UCP1). The expression changes seasonally, with higher expression during hibernation compared with the summer active state. Functional and pharmacologic analyses show that squirrel UCP1 acts as the typical thermogenic protein in vitro. Accordingly, we found that mitochondria isolated from torpid squirrel brain show a high level of palmitate-induced uncoupling. Furthermore, torpid squirrels during the hibernation season keep their brain temperature significantly elevated above ambient temperature and that of the rest of the body, including brown adipose tissue. Together, our findings suggest that UCP1 contributes to local thermogenesis in the squirrel brain, and thus supports nervous tissue function at low body temperature during hibernation.

scholarly journals Evidence for unmasking of rat brown-adipose-tissue mitochondrial GDP-binding sites in response to acute cold exposure. Effects of washing with albumin on GDP binding

1986 ◽  
Vol 233 (3) ◽  
pp. 743-747 ◽  
Author(s):  
C L Gribskov ◽  
M F Henningfield ◽  
A G Swick ◽  
R W Swick
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Binding Sites ◽  
Uncoupling Protein ◽  
Fold Increase ◽  
Scatchard Analysis ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
Brown Adipose

Rats, previously acclimated to 29 degrees C, were moved into the cold (4 degrees C) for 2 h. Scatchard analysis of GDP binding to the brown-adipose-tissue mitochondria of these animals showed a 2.3-fold increase in the number of high-affinity sites and a 1.5-fold increase in the number of low-affinity sites compared with binding in animals maintained at 29 degrees C. Immunochemical determination showed no increase in the amount of mitochondrial uncoupling protein during this period. This strongly suggests an unmasking of existing GDP-binding sites before a detectable increase in synthesis of uncoupling protein can occur. Washing with albumin increased the number of GDP-binding sites of brown-adipose-tissue mitochondria from both warm-housed and cold-exposed animals to the same extent. This indicates that the effects of washing with albumin and cold exposure are independent and additive.

Characterization and regulation of cold-induced heat shock protein expression in mouse brown adipose tissue

1995 ◽  
Vol 269 (1) ◽  
pp. R38-R47 ◽  
Author(s):  
J. M. Matz ◽  
M. J. Blake ◽  
H. M. Tatelman ◽  
K. P. Lavoi ◽  
N. J. Holbrook
Keyword(s):  
Adipose Tissue ◽  
Heat Shock ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Elevated Temperatures ◽  
Uncoupling Protein ◽  
Hsp70 Expression ◽  
Mitochondrial Uncoupling ◽  
Ambient Temperatures ◽  
Brown Adipose

The accumulation of heat shock proteins (HSPs) after the exposure of cells or organisms to elevated temperatures is well established. It is also known that a variety of other environmental and cellular metabolic stressors can induce HSP synthesis. However, few studies have investigated the effect of cold temperature on HSP expression. Here we report that exposure of Institute of Cancer Research (ICR) mice to cold ambient temperatures results in a tissue-selective induction of HSPs in brown adipose tissue (BAT) coincident with the induction of mitochondrial uncoupling protein synthesis. Cold-induced HSP expression is associated with enhanced binding of heat shock transcription factors to DNA, similar to that which occurs after exposure of cells or tissues to heat and other metabolic stresses. Adrenergic receptor antagonists were found to block cold-induced HSP70 expression in BAT, whereas adrenergic agonists induced BAT HSP expression in the absence of cold exposure. These findings suggest that norepinephrine, released in response to cold exposure, induces HSP expression in BAT. Norepinephrine appears to initiate transcription of HSP genes after binding to BAT adrenergic receptors through, as yet, undetermined signal transduction pathways. Thermogenesis results from an increase in activity and synthesis of several metabolic enzymes in BAT of animals exposed to cold challenge. The concomitant increase in HSPs may function to facilitate the translocation and activity of the enzymes involved in this process.

Effects of intravenous isoproterenol (β-agonist) administration on expression and synthesis of ovine uncoupling protein-1

1999 ◽  
Vol 1999 ◽  
pp. 164-164
Author(s):  
D.S. Finn ◽  
P. Trayhurn ◽  
J. Struthers ◽  
M.A. Lomax
Keyword(s):  
Adipose Tissue ◽  
Cold Stress ◽  
Uncoupling Protein ◽  
Uncoupling Protein 1 ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
Neonatal Life ◽  
Adrenoceptor Agonist ◽  
Brown Adipose

A crucial factor in the prevention of hypothermia in the neonatal lamb is the functional activitation of a mitochondrial uncoupling protein (UCP1) in brown adipose tissue. UCP1 disappears from lamb brown fat over the first 14 days of life (Finn et al., 1998), but it is not known whether this process can be modulated in lambs by the release of catecholamines which have been established in rodents as a mediator of the response to cold stress. This study examines the effect of administering a β-adrenoceptor agonist on the disappearance of UCP1 and UCP1 mRNA during early neonatal life, using immunohistochemistry and in situ hybridization.

Thyroxine 5'-deiodinase in brown adipose tissue of myopathic hamsters

1986 ◽  
Vol 251 (1) ◽  
pp. E8-E13 ◽  
Author(s):  
J. Kopecky ◽  
L. Sigurdson ◽  
I. R. Park ◽  
J. Himms-Hagen
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
High Fat Diet ◽  
Uncoupling Protein ◽  
High Fat ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
Endogenous Production ◽  
Deiodinase Activity ◽  
Brown Adipose

Myopathic Syrian hamsters (BIO 14.6) have less brown adipose tissue (BAT) than normal. The trophic response of this tissue to cold is smaller than normal and trophic responses to diet and to photoperiod are absent. The objective was to find out whether activity of thyroxine 5'-deiodinase in their BAT was increased normally in response to cold and thus whether a defect in endogenous production of 3,5,3'-triiodothyronine might underlie the attenuated trophic response. The effect of feeding a high-fat diet on activity of 5'-deiodinase was also studied. Cold acclimation increased thyroxine 5'-deiodinase activity in BAT of the myopathic hamster, but the total remained smaller than normal because of the smaller size. The cold-induced increase in concentration of mitochondrial uncoupling protein was also smaller than normal. The level of serum 3,5,3'-triiodothyronine was low in myopathic hamsters and remained lower than normal when they were cold-exposed or cold acclimated. Feeding the high-fat diet to myopathic hamsters resulted in a greater than normal suppression of thyroxine 5'-deiodinase activity than in normal hamsters; the normal increases in protein content and in concentration of mitochondrial uncoupling protein were absent. We conclude that the defective trophic response of BAT of the myopathic hamster is not secondary to defective regulation of its thyroxine 5'-deiodinase activity because this activity does not appear to be obligatorily linked to hypertrophy of BAT. The low level of serum 3,5,3'-triiodothyronine in the myopathic hamster may be secondary to reduced capacity for peripheral thyroxine deiodination in its BAT.

scholarly journals The possible proton translocating activity of the mitochondrial uncoupling protein of brown adipose tissue

FEBS Letters ◽  
1983 ◽  
Vol 164 (2) ◽  
pp. 272-276 ◽  
Author(s):  
F. Bouillaud ◽  
D. Ricquier ◽  
T. Gulik-Krzywicki ◽  
C.M. Gary-Bobo
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
Brown Adipose

scholarly journals Identification of a Functioning Mitochondrial Uncoupling Protein 1 in Thymus

2005 ◽  
Vol 280 (16) ◽  
pp. 15534-15543 ◽  
Author(s):  
Audrey M. Carroll ◽  
Lee R. Haines ◽  
Terry W. Pearson ◽  
Padraic G. Fallon ◽  
Caitríona M. Walsh ◽  
...  
Keyword(s):  
Metabolic Flux ◽  
Uncoupling Protein ◽  
Mitochondrial Uncoupling ◽  
Knock Out ◽  
Mitochondrial Uncoupling Protein ◽  
Rna Transcripts ◽  
Peptide Mass ◽  
Brown Adipose ◽  
Knock Out Mice ◽  
Kinetics Of

We present evidence that rat and mouse thymi contain mitochondrial uncoupling protein (UCP 1). Reverse transcriptase-PCR detected RNA transcripts for UCP 1 in whole thymus and in thymocytes. Furthermore, using antibodies to UCP 1 the protein was also detected in mitochondria isolated from whole thymus and thymocytes but not in thymus mitochondria from UCP 1 knock-out mice. Evidence for functional UCP 1 in thymus mitochondria was obtained by a comparative analysis with the kinetics of GDP binding in mitochondria from brown adipose tissue. Both tissues showed equivalentBmaxandKDvalues. In addition, a large component of the nonphosphorylating oxygen consumption by thymus mitochondria was inhibited by GDP and subsequently stimulated by addition of nanomolar concentrations of palmitate. UCP 1 was purified from thymus mitochondria by hydroxyapatite chromatography. The isolated protein was identified by peptide mass mapping and tandem mass spectrometry by using MALDI-TOF and LC-MS/MS, respectively. We conclude that the thymus contains a functioning UCP 1 that has the capacity to regulate metabolic flux and production of reactive oxygen-containing molecules in the thymus.

Measurement by radioimmunoassay of the mitochondrial uncoupling protein from brown adipose tissue of obese (ob/ob) mice and Zucker (fa/fa) rats at different ages

FEBS Letters ◽  
1985 ◽  
Vol 179 (2) ◽  
pp. 233-237 ◽  
Author(s):  
Margaret Ashwell ◽  
Susan Holt ◽  
Graham Jennings ◽  
Dorothy M. Stirling ◽  
Paul Trayhurn ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
Brown Adipose ◽  
Different Ages
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