Increased nonshivering thermogenesis, brown fat cytochrome-c oxidase activity, GDP binding, and uncoupling protein mRNA levels after short daily cold exposure of Phodopus sungorus

1990 ◽  
Vol 68 (2) ◽  
pp. 195-200 ◽  
Author(s):  
Herbert Wiesinger ◽  
Susanne Klaus ◽  
Gerhard Heldmaier ◽  
Odette Champigny ◽  
Daniel Ricquier
Keyword(s):  
Cytochrome C Oxidase ◽  
Cold Exposure ◽  
Basal Metabolic Rate ◽  
Oxidase Activity ◽  
Uncoupling Protein ◽  
Brown Fat ◽  
Phodopus Sungorus ◽  
Mrna Levels ◽  
Nonshivering Thermogenesis ◽  
Uncoupling Protein Mrna

In their natural environment, burrowing rodents experience rather fluctuating ambient temperatures and are acutely cold exposed only for short periods outside their burrows. The effect of short daily cold exposure on basal metabolic rate, nonshivering thermogenesis, brown fat thermogenesis, and uncoupling protein mRNA was studied in the Djungarian hamster, Phodopus sungorus. They were kept at 23 °C and exposed to 5 °C daily either for one 4-h period or twice for 2 h (in 12-h intervals). At the same time control hamsters were kept continuously either at thermoneutrality (23 °C) or at 5 °C. Two 2-h cold exposures daily were sufficient to increase basal metabolic rate and nonshivering thermogenesis to the same level as continuous cold exposure, whereas one 4-h cold period per day did not result in a significant increase of both parameters. Brown fat thermogenesis (as measured by cytochrome-c oxidase activity and GDP binding to the mitochondrial uncoupling protein) increased to the same extent by both treatments with short daily cold exposure. However, this increase was less than in the chronically cold-exposed hamsters. A similar result was found for uncoupling protein mRNA: both short-term cold-exposed hamsters increased uncoupling protein mRNA levels to a similar extent, but less than after chronic cold treatment. It is concluded that short daily cold exposures are sufficient to cause adaptive increases of the capacity of metabolic heat production as well as brown fat thermogenic properties.Key words: nonshivering thermogenesis, brown fat, GDP binding, uncoupling protein mRNA, Phodopus sungorus.

Brown fat and nonshivering thermogenesis in the gray mouse lemur (Microcebus murinus)

2003 ◽  
Vol 284 (3) ◽  
pp. R811-R818 ◽  
Author(s):  
F. Génin ◽  
M. Nibbelink ◽  
M. Galand ◽  
M. Perret ◽  
L. Ambid
Keyword(s):  
Metabolic Rate ◽  
Cold Exposure ◽  
Uncoupling Protein ◽  
Brown Fat ◽  
Mouse Lemur ◽  
Microcebus Murinus ◽  
Tropical Species ◽  
Daily Torpor ◽  
Nonshivering Thermogenesis ◽  
Gray Mouse Lemur

The gray mouse lemur Microcebus murinus is a rare example of a primate exhibiting daily torpor. In captive animals, we examined the metabolic rate during arousal from torpor and showed that this process involved nonshivering thermogenesis (NST). Under thermoneutrality (28°C), warming-up from daily torpor (body temperature <33°C) involved a rapid (<5 min) increase of O2 consumption that was proportional to the depth of torpor ( n = 8). The injection of a β-adrenergic agonist (isoproterenol) known to elicit NST induced a dose-dependent increase in metabolic rate ( n = 8). Moreover, maximum thermogenesis was increased by cold exposure. For the first time in this species, anatomic and histological examination using an antibody against uncoupling protein (UCP) specifically demonstrated the presence of brown fat. With the use of Western blotting with the same antibody, we showed a likely increase in UCP expression after cold exposure, suggesting that NST is also used to survive low ambient temperatures in this tropical species.

Transcriptional and posttranscriptional mechanisms in uncoupling protein mRNA response to cold

1992 ◽  
Vol 262 (1) ◽  
pp. E58-E67 ◽  
Author(s):  
S. Rehnmark ◽  
A. C. Bianco ◽  
J. D. Kieffer ◽  
J. E. Silva
Keyword(s):  
Gene Expression ◽  
Gene Transcription ◽  
Cold Exposure ◽  
Transcription Initiation ◽  
Uncoupling Protein ◽  
Mrna Levels ◽  
Brown Adipocytes ◽  
Mrna Precursor ◽  
Uncoupling Protein Mrna

Three mechanisms account for the rapid elevation and maintenance of uncoupling protein (UCP) mRNA levels in cold-exposed rats, namely, an increase in the rate of transcription initiation, an increase in the fraction of nascent UCP transcripts undergoing elongation, and stabilization of the mature UCP mRNA. The second mechanism precedes and outlasts the increase in the rate of UCP gene transcription, which is brisk but short lived. After 48 h of cold exposure, mature UCP mRNA levels are maintained elevated solely on the basis of stabilization, since the levels of both transcription initiation and fifth intron-containing transcripts (precursors) have returned to basal. Results in hypothyroid rats given 3,5,3'-triiodothyronine (T3) and in dispersed brown adipocytes show that T3 is involved both in the increase in UCP mRNA precursor level and stabilization of mature UCP mRNA. These mechanisms are rapidly reversed when the rats are returned to thermoneutrality. These coordinated transcriptional and post-transcriptional mechanisms modulating UCP gene expression ensure a rapid increase in the concentration of UCP and prevent further accumulation of the protein as physiologically adequate levels are attained.

Selective loss of uncoupling protein mRNA in brown adipose tissue on deacclimation of cold-acclimated mice

1987 ◽  
Vol 65 (11) ◽  
pp. 955-959 ◽  
Author(s):  
Hasmukh V. Patel ◽  
Karl B. Freeman ◽  
Michel Desautels
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cytochrome C Oxidase ◽  
Time Course ◽  
Uncoupling Protein ◽  
Relative Proportion ◽  
Cdna Probe ◽  
Mitochondrial Content ◽  
Brown Adipose ◽  
Uncoupling Protein Mrna

The time course of changes in the level of uncoupling protein mRNA when cold-acclimated mice were returned to a thermoneutral environment (33 °C) was examined using a cDNA probe. Upon deacclimation, there was a marked loss of uncoupling protein mRNA within 24 h, which precedes the loss of uncoupling protein from mitochondria. This loss of uncoupling protein mRNA was selective, since there was no change in the relative proportion of cytochrome c oxidase subunit IV mRNA or poly(A)+ RNA in total RNA. The results suggest that the decrease in the mitochondrial content of uncoupling protein during deacclimation is likely the result of turnover of existing protein, with very little replacement due to a lower level of its mRNA.

scholarly journals Co-ordinate decrease in the expression of the mitochondrial genome and nuclear genes for mitochondrial proteins in the lactation-induced mitochondrial hypotrophy of rat brown fat

1995 ◽  
Vol 308 (3) ◽  
pp. 749-752 ◽  
Author(s):  
I Martin ◽  
M Giralt ◽  
O Viñas ◽  
R Iglesias ◽  
T Mampel ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Mitochondrial Genome ◽  
Cytochrome C Oxidase ◽  
Molecular Mechanisms ◽  
Uncoupling Protein ◽  
Relative Content ◽  
Nuclear Genes ◽  
Mitochondrial Proteins ◽  
Mrna Levels ◽  
Brown Adipose

The relative abundance of the mitochondrial-encoded mRNAs for cytochrome c oxidase subunit II and NADH dehydrogenase subunit I was lower in brown adipose tissue (BAT) from lactating rats than in virgin controls. This decrease was in parallel with a significant decrease in mitochondrial 16 S rRNA levels and in the relative content of mitochondrial DNA in the tissue. BAT from lactating rats showed lowered mRNA expression of the nuclear-encoded genes for the mitochondrial uncoupling protein, subunit IV of cytochrome c oxidase and the adenine nucleotide translocase isoforms ANT1 and ANT2, whereas mRNA levels for the ATP synthase beta-subunit were unchanged. However, the relative content of this last protein was lower in BAT mitochondria from lactating rats than in virgin controls. It is concluded that lactation-induced mitochondrial hypotrophy in BAT is associated with a co-ordinate decrease in the expression of the mitochondrial genome and nuclear genes for mitochondrial proteins. This decrease is caused by regulatory events acting at different levels, including pre- and post-transcriptional regulation. BAT appears to be a useful model with which to investigate the molecular mechanisms involved in the co-ordination of the expression of the mitochondrial and nuclear genomes during mitochondrial biogenesis.

scholarly journals Fatty Acids Rescue the Thermogenic Function of Sympathetically Denervated Brown Fat

Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1428
Author(s):  
Qiang Cao ◽  
Shirong Wang ◽  
Huan Wang ◽  
Xin Cui ◽  
Jia Jing ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Body Temperature ◽  
Cold Exposure ◽  
Uncoupling Protein ◽  
Sympathetic Innervation ◽  
Brown Fat ◽  
Key Factors ◽  
Uncoupling Protein 1 ◽  
Physiological Factors ◽  
Brown Adipose

Sympathetic nervous system (SNS) innervation into brown adipose tissue (BAT) has been viewed as an impetus for brown fat thermogenesis. However, we surprisingly discovered that BAT SNS innervation is dispensable for mice to maintain proper body temperature during a prolonged cold exposure. Here we aimed to uncover the physiological factors compensating for maintaining brown fat thermogenesis in the absence of BAT innervation. After an initial decline of body temperature during cold exposure, mice with SNS surgical denervation in interscapular BAT gradually recovered their temperature comparable to that of sham-operated mice. The surgically denervated BAT also maintained a sizable uncoupling protein 1 (UCP1) protein along with basal norepinephrine (NE) at a similar level to that of sham controls, which were associated with increased circulating NE. Furthermore, the denervated mice exhibited increased free fatty acid levels in circulation. Indeed, surgical denervation of mice with CGI-58 deletion in adipocytes, a model lacking lipolytic capacity to release fatty acids from WAT, dramatically reduced BAT UCP1 protein and rendered the mice susceptible to cold. We conclude that circulating fatty acids and NE may serve as key factors for maintaining BAT thermogenic function and body temperature in the absence of BAT sympathetic innervation.

scholarly journals ChREBP-β regulates thermogenesis in brown adipose tissue

2020 ◽  
Vol 245 (3) ◽  
pp. 343-356 ◽  
Author(s):  
Chunchun Wei ◽  
Xianhua Ma ◽  
Kai Su ◽  
Shasha Qi ◽  
Yuangang Zhu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Uncoupling Protein ◽  
Critical Role ◽  
Active Form ◽  
Negative Regulator ◽  
Mrna Levels ◽  
Brown Adipose ◽  
Metabolic Remodeling

Brown adipose tissue (BAT) plays a critical role in energy expenditure by uncoupling protein 1 (UCP1)-mediated thermogenesis. Carbohydrate response element-binding protein (ChREBP) is one of the key transcription factors regulating de novo lipogenesis (DNL). As a constitutively active form, ChREBP-β is expressed at extremely low levels. Up to date, its functional relevance in BAT remains unclear. In this study, we show that ChREBP-β inhibits BAT thermogenesis. BAT ChREBP-β mRNA levels were elevated upon cold exposure, which prompted us to generate a mouse model overexpressing ChREBP-β specifically in BAT using the Cre/LoxP approach. ChREBP-β overexpression led to a whitening phenotype of BAT at room temperature, as evidenced by increased lipid droplet size and decreased mitochondrion content. Moreover, BAT thermogenesis was inhibited upon acute cold exposure, and its metabolic remodeling induced by long-term cold adaptation was significantly impaired by ChREBP-β overexpression. Mechanistically, ChREBP-β overexpression downregulated expression of genes involved in mitochondrial biogenesis, autophagy, and respiration. Furthermore, thermogenic gene expression (e.g. Dio2, UCP1) was markedly inhibited in BAT by the overexpressed ChREBP-β. Put together, our work points to ChREBP-β as a negative regulator of thermogenesis in brown adipocytes.

scholarly journals Adaptative decrease in expression of the mRNA for uncoupling protein and subunit II of cytochrome c oxidase in rat brown adipose tissue during pregnancy and lactation

1989 ◽  
Vol 263 (3) ◽  
pp. 965-968 ◽  
Author(s):  
I Martin ◽  
M Giralt ◽  
O Viñas ◽  
R Iglesias ◽  
T Mampel ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Mrna Expression ◽  
Cytochrome C Oxidase ◽  
Uncoupling Protein ◽  
Late Pregnancy ◽  
Brown Fat ◽  
Breeding Cycle ◽  
Brown Adipose ◽  
Pregnancy And Lactation ◽  
Brown Fat Mitochondria

Uncoupling-protein (UCP) mRNA expression is decreased to 15% of virgin control levels between days 10 and 15 of pregnancy, and remains at these low values during late pregnancy and lactation. Abrupt weaning of mid-lactating rats causes a slight but significant increase in UCP mRNA. Expression of mRNA for subunit II of cytochrome c oxidase (COII) decreased to half that of virgin control in late pregnancy and during lactation. Whereas COII mRNA expression is in step with the known modifications of brown-fat mitochondria content during the breeding cycle of the rat, UCP mRNA expression appears to be diminished much earlier than the mitochondrial proton-conductance-pathway activity. On the other hand, the reactivity of brown fat to increase expression of UCP and COII mRNAs in response to acute cold or noradrenaline treatment is not impaired during lactation.

Use of cloned cDNA sequences to measure changes in the level of brown fat uncoupling protein mRNA

1986 ◽  
Vol 14 (2) ◽  
pp. 277-277
Author(s):  
D. RICQUIER ◽  
F. BOUILLAUD ◽  
G. MORY ◽  
R. FALCOU
Keyword(s):  
Uncoupling Protein ◽  
Brown Fat ◽  
Cdna Sequences ◽  
Cloned Cdna ◽  
Uncoupling Protein Mrna

Effects of exposure temperature on brown adipose tissue uncoupling protein mRNA levels

1989 ◽  
Vol 67 (2-3) ◽  
pp. 147-151 ◽  
Author(s):  
Karl B. Freeman ◽  
Michael Heffernan ◽  
Zenobia Dhalla ◽  
Hasmukh V. Patel
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Effect Of Temperature ◽  
Initial Time ◽  
Maximal Response ◽  
Mrna Levels ◽  
Exposure Temperature ◽  
Brown Adipose ◽  
Uncoupling Protein Mrna

The effect of temperature on the amount of uncoupling protein mRNA in rat brown adipose tissue was examined after 1 and 14 days of exposure to cold. The relative amounts after 1 day, compared with rats kept at a thermoneutral temperature of 28 °C, were 3.2 at 19 °C, 3.3 at 11 °C, and 2.1 at 3 °C. This suggests that in warm-acclimated rats, a maximal response to a cold stimulus in brown adipose tissue is reached by 19 °C. In contrast to these results, the relative amounts of uncoupling protein mRNA after 14 days of cold exposure, compared with rats left at 28 °C, were 1.2 at 19 °C, 1.9 at 11 °C, and 2.1 at 3 °C. Since it is known that the amount of uncoupling protein in cold-acclimated rats increases continuously with decrease in temperature, the amount of protein reflects the mRNA levels during later times but not the initial time of exposure to cold.Key words: brown adipose tissue, uncoupling protein mRNA.

White, brite, and brown adipocytes: the evolution and function of a heater organ in mammals

2014 ◽  
Vol 92 (7) ◽  
pp. 615-626 ◽  
Author(s):  
Yongguo Li ◽  
David Lasar ◽  
Tobias Fromme ◽  
Martin Klingenspor
Keyword(s):  
Adipose Tissue ◽  
Molecular Mechanisms ◽  
Uncoupling Protein ◽  
Brown Fat ◽  
Brown Adipocyte ◽  
Nonshivering Thermogenesis ◽  
Inner Mitochondrial Membrane ◽  
Brown Adipocytes ◽  
Mitochondrial Density ◽  
Beige Adipocytes

Brown fat is a specialized heater organ in eutherian mammals. In contrast to the energy storage function of white adipocytes, brown adipocytes dissipate nutrient energy by uncoupling of mitochondrial oxidative phosphorylation, which depends on uncoupling protein 1 (UCP1). UCP1, as well as UCP2 and UCP3, belong to the family of mitochondrial carriers inserted into the inner mitochondrial membrane for metabolite trafficking between the matrix and the intermembrane space. UCP1 transports protons into the mitochondrial matrix when activated by a rise in free fatty acid levels in the cell. This UCP1-dependant proton leak drives high oxygen consumption rates in the absence of ATP synthesis and dissipates proton motive force as heat. The enormous heating capacity of brown fat is supported by dense vascularization, high rates of tissue perfusion, and high mitochondrial density in brown adipocytes. It has been known for more than 50 years that nonshivering thermogenesis in brown fat serves to maintain body temperature of neonates and small mammals in cold environments, and is used by hibernators for arousal from torpor. It has been speculated that the development of brown fat as a new source for nonshivering thermogenesis provided mammals with a unique advantage for survival in the cold. Indeed brown fat and UCP1 is found in ancient groups of mammals, like the afrotherians and marsupials. In the latter, however, the thermogenic function of UCP1 and brown fat has not been demonstrated as of yet. Notably, orthologs of all three mammalian UCP genes are also present in the genomes of bony fishes and in amphibians. Molecular phylogeny reveals a striking increase in the substitution rate of UCP1 between marsupial and eutherian lineages. At present, it seems that UCP1 only gained thermogenic function in brown adipocytes of eutherian mammals, whereas the function of UCP1 and that of the other UCPs in ectotherms remains to be identified. Evolution of thermogenic function required expression of UCP1 in a brown-adipocyte-like cell equipped with high mitochondrial density embedded in a well-vascularized tissue. Brown-adipocyte-like cells in white adipose tissue, called “brite” (brown-in-white) or “beige” adipocytes, emerge during adipogenesis and in response to cold exposure in anatomically distinct adipose tissue depots of juvenile and adult rodents. These brite adipocytes may resemble the archetypical brown adipocyte in vertebrate evolution. It is therefore of interest to elucidate the molecular mechanisms of brite adipocyte differentiation, study the bioenergetic properties of these cells, and search for the presence of related brown-adipocyte-like cells in nonmammalian vertebrates.

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