Uncoupling protein 1 in fish uncovers an ancient evolutionary history of mammalian nonshivering thermogenesis

2005 ◽  
Vol 22 (2) ◽  
pp. 150-156 ◽  
Author(s):  
Martin Jastroch ◽  
Sven Wuertz ◽  
Werner Kloas ◽  
Martin Klingenspor
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
General Interest ◽  
Nonshivering Thermogenesis ◽  
Inner Mitochondrial Membrane ◽  
Brown Adipose ◽  
History Of ◽  
Proton Leakage ◽  
Species Production

Uncoupling proteins (UCPs) increase proton leakage across the inner mitochondrial membrane. Thereby, UCP1 in brown adipose tissue dissipates proton motive force as heat. This mechanism of nonshivering thermogenesis is considered as a monophyletic trait of endothermic placental mammals that emerged about 140 million years ago and provided a crucial advantage for life in the cold. The paralogues UCP2 and UCP3 are probably not thermogenic proteins but convey mild uncoupling, which may serve to reduce the rate of mitochondrial reactive oxygen species production. Both are present in endotherms (mammals and birds), but so far only UCP2 has been identified in ectothermic vertebrates (fish and amphibia). The evolution of UCPs is of general interest in the search for the origin of mammalian UCP1-mediated nonshivering thermogenesis. We here show the presence of UCP1 and UCP3 in ectothermic teleost fish species using comparative genomics, phylogenetic inference, and gene expression analysis. In the common carp ( Cyprinus carpio), UCP1 is predominantly expressed in the liver and strongly diminished in response to cold exposure, thus contrasting the cold-induced expression of mammalian UCP1 in brown adipose tissue. UCP3 mRNA is only found in carp skeletal muscle with expression levels increased fivefold in response to fasting. Our findings disprove the monophyletic nature of UCP1 in placental mammals and demonstrate that all three members of the core UCP family were already present before the divergence of ray-finned and lobe-finned vertebrate lineages about 420 million years ago.

Corticosterone decreases nonshivering thermogenesis and increases lipid storage in brown adipose tissue

1995 ◽  
Vol 268 (1) ◽  
pp. R183-R191 ◽  
Author(s):  
A. M. Strack ◽  
M. J. Bradbury ◽  
M. F. Dallman
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Glucocorticoid Receptors ◽  
Uncoupling Protein ◽  
Lipid Storage ◽  
Scatchard Analysis ◽  
Nonshivering Thermogenesis ◽  
Diurnal Range ◽  
Brown Adipose ◽  
Intact Rats

Brown adipose tissue (BAT) contains glucocorticoid receptors; glucocorticoids are required for maintaining differentiated BAT in culture. These studies were performed to determine the effects of corticosterone on BAT thermogenic function and lipid storage. Rats were adrenalectomized and given subcutaneous corticosterone pellets in concentrations that maintained plasma corticosterone constant across the range of 0-20 micrograms/dl or were sham adrenalectomized. All variables were examined 5 days after surgery and corticosterone replacement. Measures of BAT function-thermogenic capacity [guanosine 5'-diphosphate (GDP) binding and uncoupling protein (UCP; a BAT-specific thermogenic protein)] and storage (BAT wet wt, protein, and DNA levels) were made. Plasma hormones (corticosterone, adrenocorticotropic hormone, insulin, 3,3',5-triiodothyronine, and thyroxine were measured. Corticosterone significantly affected BAT thermogenic measures: UCP content and binding of GDP to BAT mitochondria decreased with increasing corticosterone; GDP binding characteristics in BAT from similarly prepared rats examined by Scatchard analysis showed that maximum binding (Bmax) and dissociation constant (Kd) decreased with increasing corticosterone dose. BAT DNA was increased by adrenalectomy and maintained at intact levels with all doses of corticosterone; BAT lipid storage increased dramatically at corticosterone values higher than the daily mean level in intact rats. Histologically, the number and size of lipid droplets within BAT adipocytes increased markedly with increased corticosterone. White adipose depots were more sensitive to circulating corticosterone concentrations than were BAT depots and increased in weight at levels of corticosterone that were at or below the daily mean level of intact rats. We conclude that, within its diurnal range of concentration corticosterone acts to inhibit nonshivering thermogenesis and increase lipid storage.(ABSTRACT TRUNCATED AT 250 WORDS)

Caveolin-1-ablated mice survive in cold by nonshivering thermogenesis despite desensitized adrenergic responsiveness

2010 ◽  
Vol 299 (3) ◽  
pp. E374-E383 ◽  
Author(s):  
Charlotte L. Mattsson ◽  
Robert I. Csikasz ◽  
Irina G. Shabalina ◽  
Jan Nedergaard ◽  
Barbara Cannon
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Standard Dose ◽  
Acclimation Temperature ◽  
Nonshivering Thermogenesis ◽  
Wild Type ◽  
Cold Temperatures ◽  
Caveolin 1 ◽  
Brown Adipose

Caveolin-1 (Cav1)-ablated mice display impaired lipolysis in white adipose tissue. They also seem to have an impairment in brown adipose tissue function, implying that Cav1-ablated mice could encounter problems in surviving longer periods in cold temperatures. To investigate this, Cav1-ablated mice and wild-type mice were transferred to cold temperatures for extended periods of time, and parameters related to metabolism and thermogenesis were investigated. Unexpectedly, the Cav1-ablated mice survived in the cold. There were no differences between Cav1-ablated and wild-type mice with regard to food intake, in behavior related to shivering, or in body temperature. The Cav1-ablated mice had a halved total fat content independently of acclimation temperature. There was no difference in brown adipose tissue uncoupling protein-1 (UCP1) protein amount, and isolated brown fat mitochondria were thermogenically competent but displayed 30% higher thermogenic capacity. However, the β3-adrenergic receptor amount was reduced by about one-third in the Cav1-ablated mice at all acclimation temperatures. Principally in accordance with this, a higher than standard dose of norepinephrine was needed to obtain full norepinephrine-induced thermogenesis in the Cav1-ablated mice; the higher dose was also needed for the Cav1-ablated mice to be able to utilize fat as a substrate for thermogenesis. In conclusion, the ablation of Cav1 impairs brown adipose tissue function by a desensitization of the adrenergic response; however, the desensitization is not evident in the animal as it is overcome physiologically, and Cav1-ablated mice can therefore survive in prolonged cold by nonshivering thermogenesis.

Marsupial uncoupling protein 1 sheds light on the evolution of mammalian nonshivering thermogenesis

2008 ◽  
Vol 32 (2) ◽  
pp. 161-169 ◽  
Author(s):  
M. Jastroch ◽  
K. W. Withers ◽  
S. Taudien ◽  
P. B. Frappell ◽  
M. Helwig ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Genomic Library ◽  
Uncoupling Protein ◽  
Monodelphis Domestica ◽  
South American ◽  
Nonshivering Thermogenesis ◽  
Uncoupling Protein 1 ◽  
Sminthopsis Crassicaudata ◽  
Brown Adipose

Brown adipose tissue expressing uncoupling protein 1 (UCP1) is responsible for adaptive nonshivering thermogenesis giving eutherian mammals crucial advantage to survive the cold. The emergence of this thermogenic organ during mammalian evolution remained unknown as the identification of UCP1 in marsupials failed so far. Here, we unequivocally identify the marsupial UCP1 ortholog in a genomic library of Monodelphis domestica. In South American and Australian marsupials, UCP1 is exclusively expressed in distinct adipose tissue sites and appears to be recruited by cold exposure in the smallest species under investigation ( Sminthopsis crassicaudata). Our data suggest that an archetypal brown adipose tissue was present at least 150 million yr ago allowing early mammals to produce endogenous heat in the cold, without dependence on shivering and locomotor activity.

scholarly journals Alternative Polyadenylation and Differential Regulation of Ucp1: Implications for Brown Adipose Tissue Thermogenesis Across Species

2021 ◽  
Vol 8 ◽  
Author(s):  
Wen-Hsin Lu ◽  
Yao-Ming Chang ◽  
Yi-Shuian Huang
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Molecular Mechanisms ◽  
Uncoupling Protein ◽  
Alternative Polyadenylation ◽  
Proton Channel ◽  
Inner Mitochondrial Membrane ◽  
Brown Adipose ◽  
Brown Adipose Tissue Thermogenesis ◽  
Ucp1 Expression

Brown adipose tissue (BAT) is a thermogenic organ owing to its unique expression of uncoupling protein 1 (UCP1), which is a proton channel in the inner mitochondrial membrane used to dissipate the proton gradient and uncouple the electron transport chain to generate heat instead of adenosine triphosphate. The discovery of metabolically active BAT in human adults, especially in lean people after cold exposure, has provoked the “thermogenic anti-obesity” idea to battle weight gain. Because BAT can expend energy through UCP1-mediated thermogenesis, the molecular mechanisms regulating UCP1 expression have been extensively investigated at both transcriptional and posttranscriptional levels. Of note, the 3′-untranslated region (3′-UTR) of Ucp1 mRNA is differentially processed between mice and humans that quantitatively affects UCP1 synthesis and thermogenesis. Here, we summarize the regulatory mechanisms underlying UCP1 expression, report the number of poly(A) signals identified or predicted in Ucp1 genes across species, and discuss the potential and caution in targeting UCP1 for enhancing thermogenesis and metabolic fitness.

Nonshivering thermogenesis and the thermogenic capacity of brown fat in fasted and/or refed mice

1988 ◽  
Vol 254 (1) ◽  
pp. R11-R16 ◽  
Author(s):  
P. Trayhurn ◽  
G. Jennings
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cytochrome Oxidase ◽  
Oxidase Activity ◽  
Uncoupling Protein ◽  
Nonshivering Thermogenesis ◽  
Interscapular Brown Adipose Tissue ◽  
Cytochrome Oxidase Activity ◽  
Brown Adipose ◽  
Thermogenic Capacity

The effects of fasting and refeeding on nonshivering thermogenesis and the properties of brown adipose tissue have been investigated in mice. Fasting for 48 h led to a substantial reduction in the capacity for nonshivering thermogenesis, and there was no recovery of thermogenic capacity during the first 5 days of refeeding. A period of 10-15 days of refeeding was required for full restoration of thermogenic capacity. The mice were hyperphagic during the first 6 days of refeeding, but body weight was recovered after 24 h. The amount of interscapular brown adipose tissue decreased substantially on fasting, but it recovered 24 h after the initiation of refeeding. Cytochrome oxidase activity, the level of mitochondrial GDP binding, and the specific mitochondrial concentration of uncoupling protein in brown adipose tissue were each reduced by fasting. Although both GDP binding and the specific concentration of uncoupling protein rapidly returned to normal on refeeding, the activity of cytochrome oxidase was not normalized until 10 days after the end of the fast. These results indicate that a prolonged period of refeeding is required for the recovery in the capacity for nonshivering thermogenesis following a fast, a similar time course being evident for the recovery of cytochrome oxidase activity in brown adipose tissue. It is suggested that the fasting-induced reduction in the capacity for nonshivering thermogenesis is linked primarily to a loss of mitochondria from brown adipose tissue and that the normalization of thermogenic capacity is dependent on the restoration of mitochondrial mass.

Brown adipose tissue uncoupling protein content in human infants, children and adults

1986 ◽  
Vol 71 (3) ◽  
pp. 291-297 ◽  
Author(s):  
M. E. J. Lean ◽  
W. P. T. James ◽  
G. Jennings ◽  
P. Trayhurn
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Protein Content ◽  
Solid Phase ◽  
Uncoupling Protein ◽  
Inner Mitochondrial Membrane ◽  
Human Infants ◽  
Tissue Samples ◽  
Brown Adipose ◽  
Solid Phase Radioimmunoassay

1. A solid-phase radioimmunoassay is described for the estimation of the uncoupling protein content of human brown adipose tissue mitochondria, as an index of thermogenic capacity. 2. The concentration of inner mitochondrial membrane uncoupling protein was measured in brown adipose tissue samples from 48 individuals who died suddenly. 3. The uncoupling protein content of axillary adipose tissue was greater than that of perirenal adipose tissue. 4. Variations in brown adipose tissue uncoupling protein content, which would be consistent with changing thermogenic requirements and capacity, were observed in different groups of subjects. Significantly lower concentrations were found in adults and in pre-term and stillborn infants than in older infants and children.

scholarly journals Interscapular brown adipose tissue recruitment is hindered by a temperature environment of 33°C: Uncoupling protein-1 underexpression is not associated with obesity development in rats

2018 ◽  
Vol 70 (3) ◽  
pp. 567-579
Author(s):  
Gordana Juric-Lekic ◽  
Ljiljana Bedrica ◽  
Dragutin Loncar
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Mrna Expression ◽  
Uncoupling Protein ◽  
Precursor Cells ◽  
Nonshivering Thermogenesis ◽  
Uncoupling Protein 1 ◽  
Brown Adipocytes ◽  
Gold Particles ◽  
Brown Adipose

Brown adipose tissue (BAT) generates heat due to unique thermogenic UC-mitochondria, an event known as nonshivering thermogenesis. Cold, adrenergic agents, hormones, etc., activate nonshivering thermogenesis, resulting in lipid mobilization, an increase in the mitochondria and mitochondrial cristae, and increased uncoupling protein-1 (UCP1) expression and its incorporation into mitochondrial cristae. BAT precursor cells mature and contribute to BAT growth in a process known as BAT recruitment. For the first time, we herein report the effect of a thermoneutral environment of 33?C on interscapular BAT (IBAT) in rats delivered and raised at 33?C. The control animals were housed at 20?C. Thermoneutral IBAT was atrophic (73 mg vs. 191 mg) but with more adipocyte precursor cells; euthermia (37.6?C) was maintained without nonshivering thermogenesis. Although IBAT was inactive, the thermoneutral animals did not develop obesity, and on the contrary, the thermoneutral environment of 33?C hindered the rats? growth, weight (65 gm vs. 139 gm), volume (67 gm vs.136 gm) and length (12 cm vs. 16 cm). The thermoneutral brown adipocytes were smaller (7234 ?m3 vs. 9198 ?m3) with more lipids (4919 ?m3 vs. 4507 ?m3) and a smaller mitochondrial cristae area (52504 ?m2 vs. 61288 ?m2/adipocyte). Lipoprotein lipase mRNA expression was 11% (vs. 58% in control) and UCP1 mRNA expression was 34% (vs. 93% control). UCP1 immunoelectron microscopic study detected 160 UCP1-gold particles (vs. 700 in control) per UC-mitochondrion; thermoneutral brown adipocytes had 9-fold fewer UCP1-gold particles (0.34x106 vs. 2.99x106 UCP1-gold particles), and thermoneutral UC-mitochondria developed specific intramitochondrial tubular inclusions.

scholarly journals A single mutation in uncoupling protein of rat brown adipose tissue mitochondria abolishes GDP sensitivity of H+ transport.

1994 ◽  
Vol 269 (10) ◽  
pp. 7435-7438
Author(s):  
D.L. Murdza-Inglis ◽  
M. Modriansky ◽  
H.V. Patel ◽  
G. Woldegiorgis ◽  
K.B. Freeman ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Single Mutation ◽  
Brown Adipose

scholarly journals TAF7L modulates brown adipose tissue formation

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Haiying Zhou ◽  
Bo Wan ◽  
Ivan Grubisic ◽  
Tommy Kaplan ◽  
Robert Tjian
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Core Promoter ◽  
Uncoupling Protein ◽  
Dna Looping ◽  
Chromatin Interactions ◽  
Brown Adipose ◽  
Important Regulator

Brown adipose tissue (BAT) plays an essential role in metabolic homeostasis by dissipating energy via thermogenesis through uncoupling protein 1 (UCP1). Previously, we reported that the TATA-binding protein associated factor 7L (TAF7L) is an important regulator of white adipose tissue (WAT) differentiation. In this study, we show that TAF7L also serves as a molecular switch between brown fat and muscle lineages in vivo and in vitro. In adipose tissue, TAF7L-containing TFIID complexes associate with PPARγ to mediate DNA looping between distal enhancers and core promoter elements. Our findings suggest that the presence of the tissue-specific TAF7L subunit in TFIID functions to promote long-range chromatin interactions during BAT lineage specification.

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