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.

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.

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.

Thermoregulatory responses of the inbred heat-tolerant FOK rat to cold

1999 ◽  
Vol 277 (2) ◽  
pp. R362-R367 ◽  
Author(s):  
Takehiro Yahata ◽  
Fujiya Furuyama ◽  
Tomoaki Nagashima ◽  
Mitsuru Moriya ◽  
Kazue Kikuchi-Utsumi ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Uncoupling Protein ◽  
High Capacity ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
Brown Adipose ◽  
Heat Tolerant ◽  
Colonic Temperature

The responses of inbred heat-tolerant FOK rats to cold were compared with those of Wistar King A/H (WKAH) and Std:Wistar (WSTR) strains. The fall of colonic temperature during cold exposure was unexpectedly smaller in FOK than in other groups, but the onset of shivering was delayed in FOK. Norepinephrine (NE)-induced in vivo oxygen consumption and the mitochondrial uncoupling protein 1 level of brown adipose tissue (BAT) were not different among the groups, but the cold-induced increases in in vivo oxygen consumption as well as plasma glycerol and free fatty acids were higher in FOK than in other groups. In vitro NE-induced oxygen consumption of BAT was less in FOK than WSTR, but not WKAH. The magnitude of the NE-induced increase in blood flow through BAT was higher in FOK than in other groups. These results suggest that FOK paradoxically have a high capacity for nonshivering thermogenesis in spite of their high capacity for heat tolerance, probably due to an increased lipid utilization and improved circulation of BAT.

scholarly journals Seasonal changes in brown adipose tissue mitochondria in a mammalian hibernator: from gene expression to function

2016 ◽  
Vol 311 (2) ◽  
pp. R325-R336 ◽  
Author(s):  
Mallory A. Ballinger ◽  
Clair Hess ◽  
Max W. Napolitano ◽  
James A. Bjork ◽  
Matthew T. Andrews
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
The Body ◽  
Mtdna Copy Number ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Content ◽  
Mitochondrial Proteome ◽  
Mitochondrial Uncoupling Protein ◽  
Brown Adipose

Brown adipose tissue (BAT) is a thermogenic organ that is vital for hibernation in mammals. Throughout the hibernation season, BAT mitochondrial uncoupling protein 1 (UCP1) enables rapid rewarming from hypothermic torpor to periodic interbout arousals (IBAs), as energy is dissipated as heat. However, BAT's unique ability to rewarm the body via nonshivering thermogenesis is not necessary outside the hibernation season, suggesting a potential seasonal change in the regulation of BAT function. Here, we examined the BAT mitochondrial proteome and mitochondrial bioenergetics in the thirteen-lined ground squirrel ( Ictidomys tridecemlineatus) across four time points: spring, fall, torpor, and IBA. Relative mitochondrial content of BAT was estimated by measuring BAT pad mass, UCP1 protein content, and mitochondrial DNA (mtDNA) copy number. BAT mtDNA content was significantly lower in spring compared with torpor and IBA ( P < 0.05). UCP1 mRNA and protein levels were highest during torpor and IBA. Respiration rates of isolated BAT mitochondria were interrogated at each complex of the electron transport chain. Respiration at complex II was significantly higher in torpor and IBA compared with spring ( P < 0.05), suggesting an enhancement in mitochondrial respiratory capacity during hibernation. Additionally, proteomic iTRAQ labeling identified 778 BAT mitochondrial proteins. Proteins required for mitochondrial lipid translocation and β-oxidation were upregulated during torpor and IBA and downregulated in spring. These data imply that BAT bioenergetics and mitochondrial content are not static across the year, despite the year-round presence of UCP1.

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 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.

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