UCP1 is essential for adaptive adrenergic nonshivering thermogenesis

2006 ◽  
Vol 291 (2) ◽  
pp. E350-E357 ◽  
Author(s):  
Valeria Golozoubova ◽  
Barbara Cannon ◽  
Jan Nedergaard
Keyword(s):  
Adipose Tissue ◽  
Cold Acclimation ◽  
Uncoupling Protein ◽  
Nonshivering Thermogenesis ◽  
Adrenergic Stimulation ◽  
Uncoupling Protein 1 ◽  
Total Absence ◽  
Brown Adipose ◽  
Different Temperatures ◽  
Enzymatic Pathways

Participation of brown adipose tissue [through the action of the uncoupling protein-1 (UCP1)] in adaptive adrenergic nonshivering thermogenesis is recognized, but the existence of a response to adrenergic stimulation in UCP1-ablated mice implies that a mechanism for an alternative adaptive adrenergic thermogenesis may exist. Here, we have used UCP1-ablated mice to examine the existence of an alternative adaptive adrenergic nonshivering thermogenesis, examined as the oxygen consumption response to systemically injected norepinephrine into anesthetized or conscious mice acclimated to different temperatures. We confirm that UCP1-dependent adrenergic nonshivering thermogenesis is adaptive, but we demonstrate that the adrenergic UCP1-independent thermogenesis is not recruitable by cold acclimation. Thus, at least in the mouse, no other proteins or enzymatic pathways exist that can participate in or with time take over the UCP1 mediation of adaptive adrenergic nonshivering thermogenesis, even in the total absence of UCP1. UCP1 is thus the only protein capable of mediating cold acclimation-recruited adaptive adrenergic 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 A 211-bp enhancer of the rat uncoupling protein-1 (UCP-1) gene controls specific and regulated expression in brown adipose tissue

1998 ◽  
Vol 333 (2) ◽  
pp. 243-246 ◽  
Author(s):  
Anne-Marie CASSARD-DOULCIER ◽  
Chantal GELLY ◽  
Frédéric BOUILLAUD ◽  
Daniel RICQUIER
Keyword(s):  
Adipose Tissue ◽  
Transgenic Mice ◽  
Brown Adipose Tissue ◽  
Reporter Gene ◽  
Uncoupling Protein ◽  
Transcriptional Response ◽  
Adrenergic Stimulation ◽  
Uncoupling Protein 1 ◽  
Specific Expression ◽  
Brown Adipose

The uncoupling protein-1 gene is uniquely expressed in brown adipose tissue (BAT) and is positively regulated by cold exposure of animals and the sympathetic nervous system. To analyse the importance of a previously identified 211-bp enhancer [Cassard-Doulcier, Gelly, Fox, Schrementi, Raimbault, Klaus, Forest, Bouillaud and Ricquier (1993) Mol. Endocrinol. 7, 497–506] in the tissue-specific expression of this gene, transgenic mice were generated using the chloramphenicol acetyltransferase (CAT) gene as a reporter gene. One out of fourteen lines of the control transgenic mice bearing the Herpes simplex thymidine kinase (TK) promoter expressed weakly the CAT reporter gene in several tissues, whereas the other lines did not express CAT. Eight founders bearing the 211-bp enhancer-TK transgene were obtained. In six lines, no expression of CAT was detected. In one line, the expression of CAT was restricted to BAT. In another line, the expression of CAT was found in BAT and, to a lesser extent, in testis. Moreover, in these lines a marked and specific increase in the expression of the reporter gene in BAT was observed either after exposure of mice to the cold or by treating them with a β-adrenoceptor agonist drug. These results demonstrate that the 211-bp enhancer alone is sufficient to both direct and restrict expression to BAT. This enhancer also mediates the transcriptional response of the gene to β-adrenergic stimulation, although it does not contain conserved cAMP response element.

Cold-induced alterations of phospholipid fatty acyl composition in brown adipose tissue mitochondria are independent of uncoupling protein-1

2007 ◽  
Vol 293 (3) ◽  
pp. R1086-R1093 ◽  
Author(s):  
Augustine Ocloo ◽  
Irina G. Shabalina ◽  
Jan Nedergaard ◽  
Martin D. Brand
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Acclimation ◽  
Uncoupling Protein ◽  
Fatty Acyl ◽  
Wild Type ◽  
Uncoupling Protein 1 ◽  
Recruitment Process ◽  
Acyl Composition ◽  
Brown Adipose

The recruitment process induced by acclimation of mammals to cold includes a marked alteration in the acyl composition of the phospholipids of mitochondria from brown adipose tissue: increases in 18:0, 18:2( n–6), and 20:4( n–6) and decreases in 16:0, 16:1, 18:1, and 22:6( n–3). A basic question is whether these alterations are caused by changes in the concentration of uncoupling protein-1 (UCP1) or the thermogenesis it mediates—implying that they are secondary effects—or whether they are an integrated, independent part of the recruitment process. This question was addressed here using wild-type and UCP1-ablated C57BL/6 mice acclimated to 24°C or 4°C. In wild-type mice, the phospholipid fatty acyl composition of mitochondria from brown adipose tissue showed the changes in response to cold that were expected from observations in other species and strains. The changes were specific, as different changes occurred in skeletal muscle mitochondria. In UCP1-ablated mice, cold acclimation induced acyl alterations in brown adipose tissue that were qualitatively identical and quantitatively similar to those in wild-type mice. Therefore, neither the increased content of UCP1 nor mitochondrial uncoupling altered the effect of cold on acyl composition. Cold acclimation in wild-type mice had little effect on phospholipid acyl composition in muscle mitochondria, but cold-acclimation in UCP1-ablated mice caused significant alterations, probably due to sustained shivering. Thus, the alterations in brown adipose tissue phospholipid acyl composition are revealed to be an independent part of the recruitment process, and their functional significance for thermogenesis should be elucidated.

scholarly journals Uncoupling protein 1 and the capacity for nonshivering thermogenesis are components of the glucose homeostatic system

2020 ◽  
Vol 318 (2) ◽  
pp. E198-E215 ◽  
Author(s):  
Stefanie F. Maurer ◽  
Tobias Fromme ◽  
Sabine Mocek ◽  
Anika Zimmermann ◽  
Martin Klingenspor
Keyword(s):  
Adipose Tissue ◽  
Glucose Uptake ◽  
Body Mass ◽  
Uncoupling Protein ◽  
Postprandial Glucose ◽  
Oral Glucose ◽  
Metabolic Efficiency ◽  
Nonshivering Thermogenesis ◽  
Uncoupling Protein 1 ◽  
Brown Adipose

Uncoupling protein 1 (Ucp1) provides nonshivering thermogenesis (NST) fueled by the dissipation of energy from macronutrients in brown and brite adipocytes. The availability of thermogenic fuels is facilitated by the uptake of extracellular glucose. This conjunction renders thermogenic adipocytes in brown and white adipose tissue (WAT) a potential target against obesity and glucose intolerance. We employed wild-type (WT) and Ucp1-ablated mice to elucidate this relationship. In three experiments of similar setup, Ucp1-ablated mice fed a high-fat diet (HFD) had either reduced or similar body mass gain, food intake, and metabolic efficiency compared with WT mice, challenging the hypothesized role of this protein in the development of diet-induced obesity. Despite the absence of increased body mass, oral glucose tolerance was robustly impaired in Ucp1-ablated mice in response to HFD. Postprandial glucose uptake was attenuated in brown adipose tissue but enhanced in subcutaneous WAT of Ucp1-ablated mice. These differences were explainable by expression of the insulin-responsive member 4 of the facilitated glucose transporter family and fully in line with the capacity for NST in these very tissues. Thus, the postprandial glucose uptake of adipose tissues serves as a surrogate measure for Ucp1-dependent and independent capacity for NST. Collectively, our findings corroborate Ucp1 as a modulator of adipose tissue glucose uptake and systemic glucose homeostasis but challenge its hypothesized causal effect on the development of obesity.

scholarly journals Evidence for Nr4a1 as a cold-induced effector of brown fat thermogenesis

2006 ◽  
Vol 24 (1) ◽  
pp. 37-44 ◽  
Author(s):  
Timo Kanzleiter ◽  
Tatjana Schneider ◽  
Isabel Walter ◽  
Florian Bolze ◽  
Christoph Eickhorst ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Knockout Mice ◽  
Uncoupling Protein ◽  
Negative Regulator ◽  
Orphan Receptor ◽  
Peroxisome Proliferator ◽  
Nonshivering Thermogenesis ◽  
Adrenergic Stimulation ◽  
Brown Adipocytes ◽  
Brown Adipose

Acute cold exposure leads to norepinephrine release in brown adipose tissue (BAT) and activates uncoupling protein (UCP)1-mediated nonshivering thermogenesis. Chronic sympathetic stimulation is known to initiate mitochondrial biogenesis, UCP1 expression, hyperplasia of BAT, and recruitment of brown adipocytes in white adipose tissue (WAT) depots. Despite distinct functions of BAT and WAT in energy balance, only a few genes are exclusively expressed in either tissue. We identified NUR77 (Nr4a1), an orphan receptor, to be induced transiently in brown adipocytes in response to β-adrenergic stimulation and in BAT of cold-exposed mice. Subsequent reporter gene assays demonstrated an inhibitory action of NUR77 on basal and peroxisome proliferator-activated receptor (PPAR)γ/retinoid X receptor (RXR)α-mediated transactivation of the Ucp1 enhancer in heterologous cotransfection experiments. Despite this function of NUR77 in the control of Ucp1 gene expression, nonshivering thermogenesis was not affected in Nur77 knockout mice. However, we observed a superinduction of Nor1 in BAT of cold-exposed knockout mice. We conclude that NUR77 is a cold-induced negative regulator of Ucp1, but phenotypic consequences in knockout mice are compensated by functional redundancy of Nor1.

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 The Role of Uncoupling Protein 1 in the Metabolism and Adiposity of RIIβ-Protein Kinase A-Deficient Mice

2004 ◽  
Vol 18 (9) ◽  
pp. 2302-2311 ◽  
Author(s):  
Michael A. Nolan ◽  
Maria A. Sikorski ◽  
G. Stanley McKnight
Keyword(s):  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Uncoupling Protein ◽  
Mrna Level ◽  
Regulatory Subunit ◽  
Uncoupling Protein 1 ◽  
Brown Adipose ◽  
Kinase A

Abstract Mice lacking the RIIβ regulatory subunit of protein kinase A exhibit a 50% reduction in white adipose tissue stores compared with wild-type littermates and are resistant to diet-induced obesity. RIIβ−/− mice also have an increase in resting oxygen consumption along with a 4-fold increase in the brown adipose-specific mitochondrial uncoupling protein 1 (UCP1). In this study, we examined the basis for UCP1 induction and tested the hypothesis that the induced levels of UCP1 in RIIβ null mice are essential for the lean phenotype. The induction of UCP1 occurred at the protein but not the mRNA level and correlated with an increase in mitochondria in brown adipose tissue. Mice lacking both RIIβ and UCP1 (RIIβ−/−/Ucp1−/−) were created, and the key parameters of metabolism and body composition were studied. We discovered that RIIβ−/− mice exhibit nocturnal hyperactivity in addition to the increased oxygen consumption at rest. Disruption of UCP1 in RIIβ−/− mice reduced basal oxygen consumption but did not prevent the nocturnal hyperactivity. The double knockout animals also retained the lean phenotype of the RIIβ null mice, demonstrating that induction of UCP1 and increased resting oxygen consumption is not the cause of leanness in the RIIβ mutant mice.

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)

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