UCP1: The only protein able to mediate adaptive non-shivering thermogenesis and metabolic inefficiency

Nedergaard, Jan; Golozoubova, Valeria; Matthias, Anita; Asadi, Abolfazl; Jacobsson, Anders; Cannon, Barbara

doi:10.1016/s0005-2728(00)00247-4

Cited by 615Adipose Tissue and MetabolismMitochondrial Function and PathologyMetabolism, Diabetes, and Cancer

UCP1: The only protein able to mediate adaptive non-shivering thermogenesis and metabolic inefficiency

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Nedergaard, Jan, Golozoubova, Valeria, Matthias, Anita, Asadi, Abolfazl, Jacobsson, Anders, Cannon, Barbara·2001·Biochimica et Biophysica Acta (BBA) - Bioenergetics

DOI 10.1016/s0005-2728(00)00247-4

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Abstract

The uniqueness of UCP1 (as compared to UCP2/UCP3) is evident from expression analysis and ablation studies. UCP1 expression is positively correlated with metabolic inefficiency, being increased by cold acclimation (in adults or perinatally) and overfeeding, and reduced in fasting and genetic obesity. Such a simple relationship is not observable for UCP2/UCP3. Studies with UCP1-ablated animals substantiate the unique role of UCP1: the phenomenon of adaptive adrenergic non-shivering thermogenesis in the intact animal is fully dependent on the presence of UCP1, and so is any kind of cold acclimation-recruited non-shivering thermogenesis; thus UCP2/UCP3 (or any other proteins or metabolic processes) cannot substitute for UCP1 physiologically, irrespective of their demonstrated ability to show uncoupling in reconstituted systems or when ectopically expressed. Norepinephrine-induced thermogenesis in brown-fat cells is absolutely dependent on UCP1, as is the uncoupled state and the recoupling by purine nucleotides in isolated brown-fat mitochondria. Although very high UCP2/UCP3 mRNA levels are observed in brown adipose tissue of UCP1-ablated mice, there is no indication that the isolated brown-fat mitochondria are uncoupled; thus, high expression of UCP2/UCP3 does not necessarily confer to the mitochondria of a tissue a propensity for being innately uncoupled. Whereas the thermogenic effect of fatty acids in brown-fat cells is fully UCP1-dependent, this is not the case in brown-fat mitochondria; this adds complexity to the issues concerning the mechanisms of UCP1 function and the pathway from beta(3)-adrenoceptor stimulation to UCP1 activation and thermogenesis. In addition to amino acid sequences conserved in all UCPs as part of the tripartite structure, all UCPs contain certain residues associated with nucleotide binding. However, conserved amongst all UCP1s so far sequenced, and without parallel in all UCP2/UCP3, are two sequences: 144SHLHGIKP and the C-terminal sequence RQTVDC(A/T)T; these sequences may therefore be essential for the unique thermogenic function of UCP1. The level of UCP1 in the organism is basically regulated at the transcriptional level (physiologically probably mainly through the beta(3)-adrenoceptor/CREB pathway), with influences from UCP1 mRNA stability and from the delay caused by translation. It is concluded that UCP1 is unique amongst the uncoupling proteins and is the only protein able to mediate adaptive non-shivering thermogenesis and the ensuing metabolic inefficiency.

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Strong evidence of mitochondrial uncoupling property is clear for UCP-1 but still heavily debated for other UCPs.
“Importantly, although strong evidence of the mitochondrial uncoupling property is clear for UCP-1 [7,12], it is still heavily debated for the other UCPs [13,14,15].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [12]

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Houštěk, J., Andersson, U., Tvrdík, P., Nedergaard, J., & Cannon, B. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.13.7689 · Cited by 73 · see citing works
Self-citation
Norepinephrine‐Stimulated Fatty‐Acid Release and Oxygen Consumption in Isolated Hamster Brown‐Fat Cells
Nedergaard, J., & Lindberg, O. (1979) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1979.tb12948.x · Cited by 72 · see citing works
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The topology of the brown adipose tissue mitochondrial uncoupling protein determined with antibodies against its antigenic sites revealed by a library of fusion proteins.
Miroux, B., Frossard, V., Raimbault, S., Ricquier, D., & Bouillaud, F. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb06051.x · Cited by 72 · see citing works
The mitochondrial ATPase of brown adipose tissue Purification and comparison with the mitochondrial ATPase from beef heart
Cannon, B., & Vogel, G. (1977) · FEBS Letters · doi:10.1016/0014-5793(77)80169-5 · Cited by 69 · see citing works
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α- and β-adrenergic control of thermogenin mRNA expression in brown adipose tissue
Jacobsson, A., Nedergaard, J., & Cannon, B. (1986) · Bioscience Reports · doi:10.1007/bf01114756 · Cited by 68 · see citing works
Self-citation
Genomic Organization and Regulation by Dietary Fat of the Uncoupling Protein 3 and 2 Genes
Gong, D.-W., He, Y., & Reitman, M. L. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.0239 · Cited by 68 · see citing works
UCP1: The Original Uncoupling Protein—and Perhaps the Only One? New Perspectives on UCP1, UCP2, and UCP3 in the Light of the Bioenergetics of the UCP1-Ablated Mice
Nedergaard, J., Matthias, A., Golozoubova, V., Jacobsson, A., & Cannon, B. (1999) · Journal of Bioenergetics and Biomembranes · doi:10.1023/a:1005400507802 · Cited by 66 · see citing works
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The pH‐dependent reciprocal changes in contributions of ADP/ATP antiporter and aspartate/glutamate antiporter to the fatty acid‐induced uncoupling
Samartsev, V. N., MOKHOVA, E. N., & Skulachev, V. P. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)00667-4 · Cited by 65 · see citing works
Stimulation of Respiration in Brown Fat Cells by Epinephrine, Dibutyryl-3′,5′-adenosine Monophosphate, and m-Chloro(carbonyl Cyanide)phenylhydrazone
Reed, N., & Fain, J. N. (1968) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)93348-x · Cited by 64 · see citing works
Uncoupling protein‐3 gene expression in skeletal muscle during development is regulated by nutritional factors that alter circulating non‐esterified fatty acids
Brun, S., Carmona, M. C., Mampel, T., et al. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)00722-x · Cited by 63 · see citing works
Dominant Negative Regulation by c-Jun of Transcription of the Uncoupling Protein-1 Gene through a Proximal cAMP-Regulatory Element: A Mechanism for Repressing Basal and Norepinephrine-Induced Expression of the Gene before Brown Adipocyte Differentiation
Yubero, P., Barberá, M., Alvarez, R., Viñas, O., Mampel, T., Iglesias, R., Villarroya, F., & Giralt, M. (1998) · Molecular Endocrinology · doi:10.1210/mend.12.7.0137 · Cited by 63 · see citing works
Increased adipose expression of the uncoupling protein-3 gene by thiazolidinediones in Wistar fatty rats and in cultured adipocytes.
Matsuda, J., Hosoda, K., Itoh, H., Son, C., Doi, K., Hanaoka, I., Inoue, G., Nishimura, H., Yoshimasa, Y., Yamori, Y., et al. (1998) · Diabetes · doi:10.2337/diabetes.47.11.1809 · Cited by 63 · see citing works
Functional Organization of the Human Uncoupling Protein-2 Gene, and Juxtaposition to the Uncoupling Protein-3 Gene
Pecqueur, C., Cassard, A., Raimbault, S., Miroux, B., Fleury, C., Gelly, C., Bouillaud, F., & Ricquier, D. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.0146 · Cited by 60 · see citing works
Identification of [3H]prazosin binding sites in crude membranes and isolated cells of brown adipose tissue as α1-adrenergic receptors
Mohell, N., Svatengren, J., & Cannon, B. (1983) · European Journal of Pharmacology · doi:10.1016/0014-2999(83)90103-6 · Cited by 60 · see citing works
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Up-regulation of muscle UCP2 gene expression by a new β3-adrenoceptor agonist, trecadrine, in obese (cafeteria) rodents, but down-regulation in lean animals
Berraondo, B., Martí, A., Duncan, J., Trayhurn, P., & Martínez, J. (2000) · International Journal of Obesity · doi:10.1038/sj.ijo.0801097 · Cited by 60 · see citing works
Both retinoic-acid-receptor- and retinoid-X-receptor-dependent signalling pathways mediate the induction of the brown-adipose-tissue-uncoupling-protein-1 gene by retinoids
ALVAREZ, R., CHECA, M., Brun, S., VI±AS, O., Mampel, T., Iglesias, R., Giralt, M., & Villarroya, F. (1999) · Biochemical Journal · doi:10.1042/bj3450091 · Cited by 59 · see citing works
Noradrenaline stimulates glucose transport in rat brown adipocytes by activating thermogenesis. Evidence that fatty acid activation of mitochondrial respiration enhances glucose transport
Marette, A., & Bukowiecki, L. J. (1991) · Biochemical Journal · doi:10.1042/bj2770119 · Cited by 55 · see citing works
α1- and β-Adrenergic regulation of intracellular Ca2+ levels in brown adipocytes
Wilcke, M., & Nedergaard, J. (1989) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(89)92134-7 · Cited by 55 · see citing works
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Role of glucagon in metabolic acclimation to cold and heat
KUROSHIMA, A., Doi, K., & Ohno, T. (1978) · Life Sciences · doi:10.1016/0024-3205(78)90401-0 · Cited by 54 · see citing works
α1‐Adrenergic activation of brown adipocytes leads to an increased formation of inositol polyphosphates
Nånberg, E., & Putney, J. W. (1986) · FEBS Letters · doi:10.1016/0014-5793(86)80185-5 · Cited by 50 · see citing works
Topogenesis of mitochondrial inner membrane uncoupling protein. Rerouting transmembrane segments to the soluble matrix compartment.
Liu, X. J., Bell, A. W., Freeman, K. B., et al. (1988) · The Journal of Cell Biology · doi:10.1083/jcb.107.2.503 · Cited by 50 · see citing works
Differential Regulation of Uncoupling Protein-2 and Uncoupling Protein-3 Gene Expression in Brown Adipose Tissue during Development and Cold Exposure
Carmona, M. C., Valmaseda, A., Brun, S., Viñas, O., Mampel, T., Iglesias, R., Giralt, M., & Villarroya, F. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8088 · Cited by 48 · see citing works
Properties of the human long and short isoforms of the uncoupling protein‐3 expressed in yeast cells
Hinz, W., Grueninger, S., Pover, A. D., & Chiesi, M. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)01568-9 · Cited by 48 · see citing works
Brown fat activity in fasted and refed rats
Rothwell, N. J., Saville, M. E., & Stock, M. J. (1984) · Bioscience Reports · doi:10.1007/bf01140499 · Cited by 48 · see citing works
Identification of the pH Sensor for Nucleotide Binding in the Uncoupling Protein from Brown Adipose Tissue
Winkler, E., Wächter, E., & Klingenberg, M. (1997) · Biochemistry · doi:10.1021/bi962178x · Cited by 47 · see citing works
Specific Sequence Motifs of Mitochondrial Uncoupling Proteins
Ježek, P., & Urbánková, E. (2000) · IUBMB Life · doi:10.1080/713803586 · Cited by 46 · see citing works
ATP synthase subunit c expression: physiological regulation of the P1 and P2 genes
ANDERSSON, U., Houštěk, J., & Cannon, B. (1997) · Biochemical Journal · doi:10.1042/bj3230379 · Cited by 45 · see citing works
Self-citation
Interaction of mitochondrial phosphate carrier with fatty acids and hydrophobic phosphate analogs
Žáčková, M., Krämer, R., & Ježek, P. (2000) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(00)00006-6 · Cited by 44 · see citing works
Physiological activation of brown adipose tissue destabilizes thermogenin mRNA
Jacobsson, A., Cannon, B., & Nedergaard, J. (1987) · FEBS Letters · doi:10.1016/0014-5793(87)80483-0 · Cited by 44 · see citing works
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Analysis of inhibition by H89 of UCP1 gene expression and thermogenesis indicates protein kinase A mediation of β3-adrenergic signalling rather than β3-adrenoceptor antagonism by H89
Fredriksson, J. M., Thonberg, H., Ohlson, K. B. E., Ohba, K., Cannon, B., & Nedergaard, J. (2001) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/s0167-4889(01)00070-2 · Cited by 42 · see citing works
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Increased α1-adrenergic receptor density in brown adipose tissue of cold-acclimated rats and hamsters
Raasmaja, A., Mohell, N., & Nedergaard, J. (1984) · European Journal of Pharmacology · doi:10.1016/0014-2999(84)90052-9 · Cited by 41 · see citing works
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Stabilization of the mRNA for the uncoupling protein thermogenin by transcriptional/translational blockade and by noradrenaline in brown adipocytes differentiated in culture: a degradation factor induced by cessation of stimulation?
Picó, C., Herron, D. K., Palou, A., Jacobsson, A., Cannon, B., & Nedergaard, J. (1994) · Biochemical Journal · doi:10.1042/bj3020081 · Cited by 39 · see citing works
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Alpha 1-adrenergic stimulation of phosphatidylinositol turnover and respiration of brown fat cells.
Mohell, N., Wallace, M. A., & Fain, J. N. (1984) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)15070-0 · Cited by 38 · see citing works
Calorigenic effect of adrenaline and noradrenaline in the frog, Rana temporaria
Harri, M. N. E., & Hedenstam, R. (1972) · Comparative Biochemistry and Physiology Part A Physiology · doi:10.1016/0300-9629(72)90071-0 · Cited by 38 · see citing works
Gap junction permeability is diminished in proliferating vascular smooth muscle cells
Kurjiaka, D. T., Steele, T. D., Olsen, M. V., et al. (1998) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1998.275.6.c1674 · Cited by 38 · see citing works
PURINE NUCLEOTIDES AND FATTY ACIDS IN ENERGY COUPLING OF MITOCHONDRIA FROM BROWN ADIPOSE TISSUE
Cannon, B., Nicholls, D. G., & Lindberg, O. R. (1973) · Elsevier eBooks · doi:10.1016/b978-0-12-068960-6.50031-9 · Cited by 37 · see citing works
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Purification and properties of mitochondrial adenosine triphosphatase of hamster brown adipose tissue
Houštěk, J., & Drahota, Z. (1977) · Biochimica et Biophysica Acta (BBA) - Enzymology · doi:10.1016/0005-2744(77)90119-x · Cited by 35 · see citing works
Does Cytoplasmic Alkalinization Trigger Mitochondrial Energy Dissipation in the Brown Adipocyte?
Chinet, A., Friedli, C., Seydoux, J., et al. (1978) · Proceedings of the Fourth International Symposium on Polarization Phenomena in Nuclear Reactions · doi:10.1007/978-3-0348-5559-4_2 · Cited by 33 · see citing works
Hormone-sensitive lipase in brown adipose tissue: Identification and effect of cold exposure
Holm, C., Fredrikson, G., Cannon, B., & Belfrage, P. (1987) · Bioscience Reports · doi:10.1007/bf01119481 · Cited by 33 · see citing works
Self-citation
The Structural Specificity of the Nucleotide-Binding Site and the Reversible Nature of the Inhibition of Proton Conductance Induced by Bound Nucleotides in Brown-Adipose-Tissue Mitochondria
Heaton, G. M., & Nicholls, D. G. (1977) · Biochemical Society Transactions · doi:10.1042/bst0050210 · Cited by 33 · see citing works
Loss of brown adipose tissue uncoupling protein mRNA on deacclimation of cold-exposed rats
Reichling, S., Ridley, R. G., Patel, H. V., Harley, C. B., & Freeman, K. B. (1987) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(87)91470-7 · Cited by 30 · see citing works
Differential interaction of fatty acids and fatty acyl CoA esters with the purified/reconstituted brown adipose tissue mitochondrial uncoupling protein
Katiyar, S. S., & Shrago, E. S. (1991) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(91)91679-7 · Cited by 30 · see citing works
Upregulation of uncoupling protein 2 mRNA in genetic obesity: lack of an essential role for leptin, hyperphagia, increased tissue lipid content, and TNF-α
Memon, R. A., Hotamışlıgil, G. S., Wiesbrock, S. M., Uysal, K. T., Faggioni, R., Moser, A. H., Feingold, K. R., & Grünfeld, C. (2000) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/s1388-1981(99)00195-x · Cited by 28 · see citing works
High protein intake accelerates the maturation of Na, K‐ATPase in rat renal tubules
Jakobsson, B., & Aperia, A. C. (1990) · Acta Physiologica Scandinavica · doi:10.1111/j.1748-1716.1990.tb08890.x · Cited by 28 · see citing works
High-fat feeding reduced muscle uncoupling protein 3 expression in rats
Corbalán, M. S., Margareto, J., Martínez, J. A., et al. (1999) · Journal of Physiology and Biochemistry · doi:10.1007/bf03655608 · Cited by 28 · see citing works
The central matrix loop drives import of uncoupling protein 1 into mitochondria
Schleiff, E., & McBride, H. M. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.12.2267 · Cited by 27 · see citing works
Adrenergic modulation of intracellular pH in isolated brown fat cells from hamster and rat
Lee, S. C., Hamilton, J. S., Trammell, T., et al. (1994) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1994.267.2.c349 · Cited by 25 · see citing works
Mechanism of norepinephrine stimulation of glucose transport in isolated rat brown adipocytes.
Marette, A., & Bukowiecki, L. J. (1990) · PubMed · Cited by 24 · see citing works
Selective loss of uncoupling protein mRNA in brown adipose tissue on deacclimation of cold-acclimated mice
Patel, H. V., Freeman, K. B., & Desautels, M. (1987) · Biochemistry and Cell Biology · doi:10.1139/o87-124 · Cited by 24 · see citing works
Endogenous mutations in human uncoupling protein 3 alter its functional properties
Brown, A. M., Dolan, J. W., Willi, S., Garvey, W., & Argyropoulos, G. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)01708-1 · Cited by 23 · see citing works
The novel thermogenic β-adrenergic agonist Ro 16-8714 increases the interscapular brown-fat β-receptor-adenylate cyclase and the uncoupling-protein mRNA level in obese (fa/fa) Zucker rats
Muzzin, P., Revelli, J. P., Ricquier, D., Meier, M. K., Assimacopoulos‐Jeannet, F., & Giacobino, J.-P. (1989) · Biochemical Journal · doi:10.1042/bj2610721 · Cited by 23 · see citing works
Metabolic effects of β, α1, and α2 adrenoceptor activation on brown adipocytes isolated from the perirenal adipose tissue of fetal lambs
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Immunological detection of cDNA clones encoding the uncoupling protein of brown adipose tissue: Evidence for an antigenic determinant within the C-terminal eleven amino acids
Ridley, R. G., Patel, H. V., Parfett, C. L. J., Olynyk, K. A., Reichling, S., & Freeman, K. B. (1986) · Bioscience Reports · doi:10.1007/bf01145183 · Cited by 20 · see citing works
Evidence for a modulating effect of NA+/H+ exchange on the metabolic response of rat brown adipose tissue
Giovannini, P., Seydoux, J., & Girardier, L. (1988) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/bf00585114 · Cited by 19 · see citing works
Mammalian mitochondrial inner membrane cationic and neutral amino acid carriers
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Systemic effects of epinephrine in the frog
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Mitochondrial import of the long and short isoforms of human uncoupling protein 3
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Use of retinoic acid as a fluorescent probe to study conformational change of the albumin molecule.
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Differential effects of noradrenaline and glucagon on lipolysis and fatty‐acid utilization in brown adipose tissue
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On the Mechanism of Transport by the Uncoupling Protein from Brown Adipose Tissue Mitochondria
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NEW MEMBERS OF UNCOUPLING PROTEIN FAMILY IMPLICATED IN ENERGY METABOLISM
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Effect of adrenaline and nor-adrenaline on the oxidative metabolism of the Indian garden lizard Calotes versicolor.
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Flagged first, then by citations

Research works printed but not linked: 12

J. Nedergaard, B. Cannon, in: L. Ernster (Ed.), New Com- prehensive Biochemistry, vol. 23: Molecular Mechanisms in Bioenergetics, Elsevier, Amsterdam, 1992, pp. 385^420.
W.H. Cottle, L.D. Carlson, Proc. Soc. Exp. Biol. Med. 92 (1956) 845^849.
J. Nedergaard, E. Connolly, B. Cannon, in: P. Trayhurn, D.G. Nicholls (Eds.), Brown Adipose Tissue, Edward Ar- nold, London, 1986, pp. 152^213.
R.S. Surwit, S. Wang, A.E. Petro, D. Sanchis, S. Raimbault, D. Ricquier, S. Collins, Proc. Natl. Acad. Sci. USA 95 (1998) 4061^4065.
M. Ashwell, G. Jennings, P. Trayhurn, Biochem. Soc. Trans. 11 (1983) 727^728.
B. Cannon, D.G. Nicholls, O. Lindberg, in: G.F. Azzone et al. (Eds.), Mechanisms in Bioenergetics, Academic Press, New York, 1973, pp. 357^364.
E. Rial, D.G. Nicholls, in: A. Azzi, K.A. Nalecz, M.J. Nalecz, L. Wojtczak (Eds.), Anion Carriers of Mitochon- drial Membranes, Springer-Verlag, Berlin, 1989, pp. 261^ 268.
P.J. Strieleman, C.E. Elson, E. Shrago, Fed. Proc. 42 (1983) 1324^1324.
G.M. Heaton, D.G. Nicholls, Biochem. Soc. Trans. 5 (1977) 210^212.
A. Chinet, C. Friedli, J. Seydoux, L. Girardier, in: L. Gir- ardier, J. Seydoux (Eds.), E¡ectors of Thermogenesis, Ex- perientia Suppl. 32 (1978) 25^32.
B. Cannon, J. Nedergaard, U. Sundin, in: X.J. Musacchia, L. Jansky (Eds.), Survival in the Cold: Hibernation and other Adaptations, Elsevier-North-Holland, Amsterdam, 1981, pp. 99^120.
S. Klaus, S. Raimbault, F. Bouillaud, D. Ricquier, M. Gessner, K.D. Ju « rgens, in: F. Geiser, A.J. Hulbert, S.C. Nicol (Eds.), Adaptions to the Cold. Tenth International Hibernation Symposium, University of New England Press, Armidale, 1996.

Sorted by citations

Brown Adipose Tissue: Function and Physiological Significance
CANNON, B., & NEDERGAARD, J. (2004) · Physiological Reviews · doi:10.1152/physrev.00015.2003 · Cited by 6,433 · see citing works
Self-citation
Metabolism and function of coenzyme Q
Turunen, M., Olsson, J., & Dallner, G. (2004) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2003.11.012 · Cited by 1,026 · see citing works
The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissue
Zingaretti, M. C., Crosta, F., Vitali, A., Guerrieri, M., Frontini, A., Cannon, B., Nedergaard, J., & Cinti, S. (2009) · The FASEB Journal · doi:10.1096/fj.09-133546 · Cited by 725 · see citing works
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Nonshivering thermogenesis and its adequate measurement in metabolic studies
Cannon, B., & Nedergaard, J. (2011) · Journal of Experimental Biology · doi:10.1242/jeb.050989 · Cited by 677 · see citing works
Self-citation
Adiponectin regulation and function
Fang, H., & Judd, R. L. (2018) · Comprehensive physiology · doi:10.1002/cphy.c170046 · Cited by 631 · see citing works
p38 Mitogen-Activated Protein Kinase Is the Central Regulator of Cyclic AMP-Dependent Transcription of the Brown Fat Uncoupling Protein 1 Gene
Cao, W., Daniel, K. W., Robidoux, J., Puigserver, P., Medvedev, A. V., Bai, X., Floering, L. M., Spiegelman, B. M., & Collins, S. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.7.3057-3067.2004 · Cited by 605 · see citing works
Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases
Demine, S., Renard, P., & Arnould, T. (2019) · Cells · doi:10.3390/cells8080795 · Cited by 476 · see citing works
“Importantly, although strong evidence of the mitochondrial uncoupling property is clear for UCP-1 [7,12], it is still heavily debated for the other UCPs [13–15].”
Background
Superoxide Activates Mitochondrial Uncoupling Protein 2 from the Matrix Side
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Mitochondrial uncoupling as a target for drug development for the treatment of obesity.
Harper, J. A., Dickinson, K., & Brand, M. D. (2001) · Obesity Reviews · doi:10.1046/j.1467-789x.2001.00043.x · Cited by 250 · see citing works
Physiological Increases in Uncoupling Protein 3 Augment Fatty Acid Oxidation and Decrease Reactive Oxygen Species Production Without Uncoupling Respiration in Muscle Cells
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Pharmacologic Effects of FGF21 Are Independent of the “Browning” of White Adipose Tissue
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Postprandial Oxidative Metabolism of Human Brown Fat Indicates Thermogenesis
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Uncoupling proteins: A role in protection against reactive oxygen species—or not?
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A liver stress-endocrine nexus promotes metabolic integrity during dietary protein dilution
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The FGF21-CCL11 Axis Mediates Beiging of White Adipose Tissues by Coupling Sympathetic Nervous System to Type 2 Immunity
Huang, Z., Zhong, L., Lee, J. T. H., Zhang, J., Wu, D., Geng, L., Wang, Y., Wong, C.-M., & Xu, A. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.08.003 · Cited by 147 · see citing works
Production of endogenous matrix superoxide from mitochondrial complex I leads to activation of uncoupling protein 3
Talbot, D. A., Lambert, A. J., & Brand, M. D. (2004) · FEBS Letters · doi:10.1016/s0014-5793(03)01386-3 · Cited by 131 · see citing works
RFamide Peptide QRFP43 Causes Obesity with Hyperphagia and Reduced Thermogenesis in Mice
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Authors: Nedergaard, J., Golozoubova, V., Matthias, A., Asadi, A., Jacobsson, A., & Cannon, B.
Affiliations: Stockholm University (SE)
Corresponding author: Nedergaard, Jan
ORCID: Nedergaard, Jan
Jacobsson, Anders
Cannon, Barbara
Venue: Biochimica et Biophysica Acta (BBA) - Bioenergetics
Publisher: Elsevier BV
Published: 2001-03
Volume: 1504
Issue: 1
Pages: 82-106
ISSN: 0005-2728 (ISSN-L)
DOI: 10.1016/s0005-2728(00)00247-4
OpenAlex: W2075282827
Cited by: 615
References: 137
Citations by year: 2026: 11 · 2025: 28 · 2024: 33 · 2023: 23 · 2022: 25 · 2021: 32 · 2020: 50 · 2019: 31 · 2018: 33 · 2017: 36 · 2016: 37 · 2015: 20 · 2014: 20 · 2013: 18 · 2012: 17
FWCI: 3.61
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 4522 d)
Locations: Biochimica et Biophysica Acta (BBA) - Bioenergetics (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: uncoupling proteins, non-shivering thermogenesis, brown adipose tissue, cold acclimation, UCP2, UCP3, beta3-adrenergic receptor, CREB, norepinephrine, mitochondrial uncoupling, purine nucleotides, obesity, overfeeding, fasting
MeSH terms: Acclimatization, Uncoupling Protein 1, Amino Acid Sequence, Animals, Animals, Newborn, Adipose Tissue, Brown, Carrier Proteins, Cells, Cultured, Gene Expression Regulation, Humans, Ion Channels, Membrane Potentials, Membrane Proteins, Mitochondria, Mitochondria, Liver, Models, Chemical, Norepinephrine, Obesity, Oxygen Consumption, RNA, Messenger, Uncoupling Agents, Cyclic AMP Response Element-Binding Protein, Adipocytes, Thermogenesis, Mitochondrial Proteins

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UCP1: The only protein able to mediate adaptive non-shivering thermogenesis and metabolic inefficiency

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