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Gene Review

Ucp1  -  uncoupling protein 1 (mitochondrial,...

Mus musculus

Synonyms: AI385626, Mitochondrial brown fat uncoupling protein 1, Slc25a7, Solute carrier family 25 member 7, Thermogenin, ...
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Disease relevance of Ucp1


Psychiatry related information on Ucp1


High impact information on Ucp1

  • The gene Ucp2 is a member of a family of genes found in animals and plants, encoding a protein homologous to the brown fat uncoupling protein Ucp1 (refs 1-3) [7].
  • Ectopic expression of PGC-1 in white adipose cells activates expression of UCP-1 and key mitochondrial enzymes of the respiratory chain, and increases the cellular content of mitochondrial DNA [8].
  • PGC-1 greatly increases the transcriptional activity of PPARgamma and the thyroid hormone receptor on the uncoupling protein (UCP-1) promoter [8].
  • The males' white adipose tissue contains cells that exhibit the distinctive multilocular appearance of brown adipocytes, and expresses the uncoupling protein 1 (UCP1), a specific marker of brown fat [9].
  • To determine whether uncoupling respiration from oxidative phosphorylation in skeletal muscle is a suitable treatment for obesity and type 2 diabetes, we generated transgenic mice expressing the mitochondrial uncoupling protein (Ucp) in skeletal muscle [10].

Chemical compound and disease context of Ucp1


Biological context of Ucp1


Anatomical context of Ucp1


Associations of Ucp1 with chemical compounds


Regulatory relationships of Ucp1

  • Wnt10b blocks brown adipose tissue development and expression of UCP1 when expressed from the fatty acid binding protein 4 promoter, even when mice are administered a beta3-agonist [25].
  • These findings indicate that overexpression of GLUT4 up-regulates UCP3 expression in skeletal muscle and down-regulates UCP1 expression in BAT, possibly by increasing the rate of glucose uptake into these tissues [26].
  • The ability of individual beta AR subtypes to regulate Ucp expression was examined with combinations of selective beta-adrenergic agonists and antagonists [27].
  • In peripheral tissue, leptin up-regulated BAT UCP1 mRNA expression and reduced fat depositions in this tissue [28].
  • The absence of MCR4 blocked leptin's ability to increase UCP1 mRNA in both brown and white adipose tissue, but not its ability to reduce food consumption [29].

Other interactions of Ucp1


Analytical, diagnostic and therapeutic context of Ucp1


  1. Transgenic UCP1 in white adipocytes modulates mitochondrial membrane potential. Baumruk, F., Flachs, P., Horáková, M., Floryk, D., Kopecký, J. FEBS Lett. (1999) [Pubmed]
  2. Role of leptin in peroxisome proliferator-activated receptor gamma coactivator-1 expression. Kakuma, T., Wang, Z.W., Pan, W., Unger, R.H., Zhou, Y.T. Endocrinology (2000) [Pubmed]
  3. Synergistic gene interactions control the induction of the mitochondrial uncoupling protein (Ucp1) gene in white fat tissue. Koza, R.A., Hohmann, S.M., Guerra, C., Rossmeisl, M., Kozak, L.P. J. Biol. Chem. (2000) [Pubmed]
  4. Hibernoma development in transgenic mice identifies brown adipose tissue as a novel target of aldosterone action. Zennaro, M.C., Le Menuet, D., Viengchareun, S., Walker, F., Ricquier, D., Lombès, M. J. Clin. Invest. (1998) [Pubmed]
  5. An upstream enhancer regulating brown-fat-specific expression of the mitochondrial uncoupling protein gene. Kozak, U.C., Kopecky, J., Teisinger, J., Enerbäck, S., Boyer, B., Kozak, L.P. Mol. Cell. Biol. (1994) [Pubmed]
  6. Agouti-related protein-deficient mice display an age-related lean phenotype. Wortley, K.E., Anderson, K.D., Yasenchak, J., Murphy, A., Valenzuela, D., Diano, S., Yancopoulos, G.D., Wiegand, S.J., Sleeman, M.W. Cell metabolism. (2005) [Pubmed]
  7. Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production. Arsenijevic, D., Onuma, H., Pecqueur, C., Raimbault, S., Manning, B.S., Miroux, B., Couplan, E., Alves-Guerra, M.C., Goubern, M., Surwit, R., Bouillaud, F., Richard, D., Collins, S., Ricquier, D. Nat. Genet. (2000) [Pubmed]
  8. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Puigserver, P., Wu, Z., Park, C.W., Graves, R., Wright, M., Spiegelman, B.M. Cell (1998) [Pubmed]
  9. Adipose tissue reduction in mice lacking the translational inhibitor 4E-BP1. Tsukiyama-Kohara, K., Poulin, F., Kohara, M., DeMaria, C.T., Cheng, A., Wu, Z., Gingras, A.C., Katsume, A., Elchebly, M., Spiegelman, B.M., Harper, M.E., Tremblay, M.L., Sonenberg, N. Nat. Med. (2001) [Pubmed]
  10. Skeletal muscle respiratory uncoupling prevents diet-induced obesity and insulin resistance in mice. Li, B., Nolte, L.A., Ju, J.S., Han, D.H., Coleman, T., Holloszy, J.O., Semenkovich, C.F. Nat. Med. (2000) [Pubmed]
  11. Up-regulation of muscle uncoupling protein 3 gene expression in mice following high fat diet, dietary vitamin A supplementation and acute retinoic acid-treatment. Felipe, F., Bonet, M.L., Ribot, J., Palou, A. Int. J. Obes. Relat. Metab. Disord. (2003) [Pubmed]
  12. Involvement of hypothalamic histamine H1 receptor in the regulation of feeding rhythm and obesity. Masaki, T., Chiba, S., Yasuda, T., Noguchi, H., Kakuma, T., Watanabe, T., Sakata, T., Yoshimatsu, H. Diabetes (2004) [Pubmed]
  13. Leptin and corticosterone have opposite effects on food intake and the expression of UCP1 mRNA in brown adipose tissue of lep(ob)/lep(ob) mice. Arvaniti, K., Ricquier, D., Champigny, O., Richard, D. Endocrinology (1998) [Pubmed]
  14. Nicotine induces uncoupling protein 1 in white adipose tissue of obese mice. Yoshida, T., Sakane, N., Umekawa, T., Kogure, A., Kondo, M., Kumamoto, K., Kawada, T., Nagase, I., Saito, M. Int. J. Obes. Relat. Metab. Disord. (1999) [Pubmed]
  15. Brown adipocytes differentiated in vitro can express the gene for the uncoupling protein thermogenin: effects of hypothyroidism and norepinephrine. Rehnmark, S., Kopecký, J., Jacobsson, A., Néchad, M., Herron, D., Nelson, B.D., Obregon, M.J., Nedergaard, J., Cannon, B. Exp. Cell Res. (1989) [Pubmed]
  16. Transcriptional synergy and the regulation of Ucp1 during brown adipocyte induction in white fat depots. Xue, B., Coulter, A., Rim, J.S., Koza, R.A., Kozak, L.P. Mol. Cell. Biol. (2005) [Pubmed]
  17. RIP140-targeted repression of gene expression in adipocytes. Christian, M., Kiskinis, E., Debevec, D., Leonardsson, G., White, R., Parker, M.G. Mol. Cell. Biol. (2005) [Pubmed]
  18. Thermogenic responses in brown fat cells are fully UCP1-dependent. UCP2 or UCP3 do not substitute for UCP1 in adrenergically or fatty scid-induced thermogenesis. Matthias, A., Ohlson, K.B., Fredriksson, J.M., Jacobsson, A., Nedergaard, J., Cannon, B. J. Biol. Chem. (2000) [Pubmed]
  19. Sequestration of thermogenic transcription factors in the cytoplasm during development of brown adipose tissue. Rim, J.S., Xue, B., Gawronska-Kozak, B., Kozak, L.P. J. Biol. Chem. (2004) [Pubmed]
  20. The bioenergetics of brown fat mitochondria from UCP1-ablated mice. Ucp1 is not involved in fatty acid-induced de-energization ("uncoupling"). Matthias, A., Jacobsson, A., Cannon, B., Nedergaard, J. J. Biol. Chem. (1999) [Pubmed]
  21. Selective activation of mitogen-activated protein (MAP) kinase kinase 3 and p38alpha MAP kinase is essential for cyclic AMP-dependent UCP1 expression in adipocytes. Robidoux, J., Cao, W., Quan, H., Daniel, K.W., Moukdar, F., Bai, X., Floering, L.M., Collins, S. Mol. Cell. Biol. (2005) [Pubmed]
  22. Mechanism of amelioration of insulin resistance by beta3-adrenoceptor agonist AJ-9677 in the KK-Ay/Ta diabetic obese mouse model. Kato, H., Ohue, M., Kato, K., Nomura, A., Toyosawa, K., Furutani, Y., Kimura, S., Kadowaki, T. Diabetes (2001) [Pubmed]
  23. Retinoids activate proton transport by the uncoupling proteins UCP1 and UCP2. Rial, E., González-Barroso, M., Fleury, C., Iturrizaga, S., Sanchis, D., Jiménez-Jiménez, J., Ricquier, D., Goubern, M., Bouillaud, F. EMBO J. (1999) [Pubmed]
  24. Opposite actions of testosterone and progesterone on UCP1 mRNA expression in cultured brown adipocytes. Rodriguez, A.M., Monjo, M., Roca, P., Palou, A. Cell. Mol. Life Sci. (2002) [Pubmed]
  25. Effects of Wnt signaling on brown adipocyte differentiation and metabolism mediated by PGC-1alpha. Kang, S., Bajnok, L., Longo, K.A., Petersen, R.K., Hansen, J.B., Kristiansen, K., MacDougald, O.A. Mol. Cell. Biol. (2005) [Pubmed]
  26. Overexpression of GLUT4 in mice causes up-regulation of UCP3 mRNA in skeletal muscle. Tsuboyama-Kasaoka, N., Tsunoda, N., Maruyama, K., Takahashi, M., Kim, H., Cooke, D.W., Lane, M.D., Ezaki, O. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  27. Regulation of the uncoupling protein gene (Ucp) by beta 1, beta 2, and beta 3-adrenergic receptor subtypes in immortalized brown adipose cell lines. Rohlfs, E.M., Daniel, K.W., Premont, R.T., Kozak, L.P., Collins, S. J. Biol. Chem. (1995) [Pubmed]
  28. Corticotropin-releasing hormone-mediated pathway of leptin to regulate feeding, adiposity, and uncoupling protein expression in mice. Masaki, T., Yoshimichi, G., Chiba, S., Yasuda, T., Noguchi, H., Kakuma, T., Sakata, T., Yoshimatsu, H. Endocrinology (2003) [Pubmed]
  29. Targeted deletion of melanocortin receptor subtypes 3 and 4, but not CART, alters nutrient partitioning and compromises behavioral and metabolic responses to leptin. Zhang, Y., Kilroy, G.E., Henagan, T.M., Prpic-Uhing, V., Richards, W.G., Bannon, A.W., Mynatt, R.L., Gettys, T.W. FASEB J. (2005) [Pubmed]
  30. Lack of obesity and normal response to fasting and thyroid hormone in mice lacking uncoupling protein-3. Gong, D.W., Monemdjou, S., Gavrilova, O., Leon, L.R., Marcus-Samuels, B., Chou, C.J., Everett, C., Kozak, L.P., Li, C., Deng, C., Harper, M.E., Reitman, M.L. J. Biol. Chem. (2000) [Pubmed]
  31. Linkage of the gene for uncoupling protein to esterase-1,2 and haptoglobin in the rat. Otsen, M., Den Bieman, M., van Zutphen, L.F. J. Hered. (1993) [Pubmed]
  32. Brown adipose tissue response to cafeteria diet-feeding involves induction of the UCP2 gene and is impaired in female rats as compared to males. Roca, P., Rodriguez, A.M., Oliver, P., Bonet, M.L., Quevedo, S., Picó, C., Palou, A. Pflugers Arch. (1999) [Pubmed]
  33. Expression of the uncoupling protein 1 from the aP2 gene promoter stimulates mitochondrial biogenesis in unilocular adipocytes in vivo. Rossmeisl, M., Barbatelli, G., Flachs, P., Brauner, P., Zingaretti, M.C., Marelli, M., Janovská, P., Horáková, M., Syrový, I., Cinti, S., Kopecký, J. Eur. J. Biochem. (2002) [Pubmed]
  34. Up-regulation of liver uncoupling protein-2 mRNA by either fish oil feeding or fibrate administration in mice. Tsuboyama-Kasaoka, N., Takahashi, M., Kim, H., Ezaki, O. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  35. Peroxisome proliferator-activated receptor gamma agonism increases the capacity for sympathetically mediated thermogenesis in lean and ob/ob mice. Sell, H., Berger, J.P., Samson, P., Castriota, G., Lalonde, J., Deshaies, Y., Richard, D. Endocrinology (2004) [Pubmed]
  36. Mechanism of ubiquitous expression of mouse uncoupling protein 2 mRNA: control by cis-acting DNA element in 5'-flanking region. Yoshitomi, H., Yamazaki, K., Tanaka, I. Biochem. J. (1999) [Pubmed]
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