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Gene Review

Ucp3  -  uncoupling protein 3 (mitochondrial,...

Mus musculus

Synonyms: AI645527, Mitochondrial uncoupling protein 3, Slc25a9, Solute carrier family 25 member 9, UCP 3, ...
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Disease relevance of Ucp3

  • Ucp3 has been proposed to influence metabolic efficiency and is a candidate obesity gene [1].
  • Metabolic efficiency (gram weight gain/kcal ingested) was similar between Ucp3 overexpressors, WT and Ucp3 (-/-) mice [2].
  • UCP3Tg mice had lower body weights and were less metabolically efficient than wild-type or Ucp3-/- mice, but they were not hyperphagic [3].
  • Increased gene expression of brown fat uncoupling protein (UCP)1 and skeletal muscle UCP2 and UCP3 in MAC16-induced cancer cachexia [4].
  • SKM UCP3 mRNA rose fivefold during development of hypothermia and was correlated with an LPS-induced increase in plasma free fatty acid concentration [5].

Psychiatry related information on Ucp3


High impact information on Ucp3


Chemical compound and disease context of Ucp3


Biological context of Ucp3


Anatomical context of Ucp3


Associations of Ucp3 with chemical compounds

  • Levels of muscle Ucp3 mRNA are increased by thyroid hormone and fasting [1].
  • In conjunction with our observed increases in CoA and carnitine in muscle of Ucp3 overexpressors, the findings support the hypothesized role for Ucp3 in facilitating fatty acid oxidation in muscle [2].
  • The murine UCP3 promoter is activated by fatty acids through either PPARalpha or PPARdelta but not by PPARgamma or retinoid X receptor alone [17].
  • We have hypothesized that increased glucose flux in skeletal muscles may lead to increased UCP3 expression [22].
  • UCP3 mRNA levels were also regulated by dexamethasone, leptin, and starvation, albeit differently in muscle and brown adipose tissue [23].

Regulatory relationships of Ucp3

  • These results suggest that in the adult rodent heart, UCP-3 expression is regulated by PPARalpha [24].
  • 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 [22].
  • Neither UCP-2 nor UCP-3 was up-regulated by insulin in wild-type and IRS-1-deficient brown adipocytes [25].

Other interactions of Ucp3


Analytical, diagnostic and therapeutic context of Ucp3


  1. 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]
  2. Constitutive UCP3 overexpression at physiological levels increases mouse skeletal muscle capacity for fatty acid transport and oxidation. Bezaire, V., Spriet, L.L., Campbell, S., Sabet, N., Gerrits, M., Bonen, A., Harper, M.E. FASEB J. (2005) [Pubmed]
  3. Effects of the presence, absence, and overexpression of uncoupling protein-3 on adiposity and fuel metabolism in congenic mice. Costford, S.R., Chaudhry, S.N., Salkhordeh, M., Harper, M.E. Am. J. Physiol. Endocrinol. Metab. (2006) [Pubmed]
  4. Increased gene expression of brown fat uncoupling protein (UCP)1 and skeletal muscle UCP2 and UCP3 in MAC16-induced cancer cachexia. Bing, C., Brown, M., King, P., Collins, P., Tisdale, M.J., Williams, G. Cancer Res. (2000) [Pubmed]
  5. Impact of endotoxin on UCP homolog mRNA abundance, thermoregulation, and mitochondrial proton leak kinetics. Yu, X.X., Barger, J.L., Boyer, B.B., Brand, M.D., Pan, G., Adams, S.H. Am. J. Physiol. Endocrinol. Metab. (2000) [Pubmed]
  6. Uncoupling protein 3 and physical activity: the role of uncoupling protein 3 in energy metabolism revisited. Schrauwen, P., Hesselink, M. The Proceedings of the Nutrition Society. (2003) [Pubmed]
  7. Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean. Clapham, J.C., Arch, J.R., Chapman, H., Haynes, A., Lister, C., Moore, G.B., Piercy, V., Carter, S.A., Lehner, I., Smith, S.A., Beeley, L.J., Godden, R.J., Herrity, N., Skehel, M., Changani, K.K., Hockings, P.D., Reid, D.G., Squires, S.M., Hatcher, J., Trail, B., Latcham, J., Rastan, S., Harper, A.J., Cadenas, S., Buckingham, J.A., Brand, M.D., Abuin, A. Nature (2000) [Pubmed]
  8. Targeted disruption of H3 receptors results in changes in brain histamine tone leading to an obese phenotype. Takahashi, K., Suwa, H., Ishikawa, T., Kotani, H. J. Clin. Invest. (2002) [Pubmed]
  9. Inhibition of hypothalamic fatty acid synthase triggers rapid activation of fatty acid oxidation in skeletal muscle. Cha, S.H., Hu, Z., Chohnan, S., Lane, M.D. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  10. 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]
  11. Pharmacology: uncoupling the agony from ecstasy. Mills, E.M., Banks, M.L., Sprague, J.E., Finkel, T. Nature (2003) [Pubmed]
  12. Genetic linkage of uncoupling proteins (UCP2 and UCP3) with body weight regulation. Jaberi, E. Asia Pacific journal of clinical nutrition. (2004) [Pubmed]
  13. UCP3 and thyroid hormone involvement in methamphetamine-induced hyperthermia. Sprague, J.E., Mallett, N.M., Rusyniak, D.E., Mills, E. Biochem. Pharmacol. (2004) [Pubmed]
  14. 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]
  15. UCP3 and its putative function: consistencies and controversies. Harper, M.E., Dent, R.M., Bezaire, V., Antoniou, A., Gauthier, A., Monemdjou, S., McPherson, R. Biochem. Soc. Trans. (2001) [Pubmed]
  16. Thyroid hormones directly activate the expression of the human and mouse uncoupling protein-3 genes through a thyroid response element in the proximal promoter region. Solanes, G., Pedraza, N., Calvo, V., Vidal-Puig, A., Lowell, B.B., Villarroya, F. Biochem. J. (2005) [Pubmed]
  17. Developmental and Tissue-Specific Involvement of Peroxisome Proliferator-Activated Receptor-{alpha} in the Control of Mouse Uncoupling Protein-3 Gene Expression. Pedraza, N., Rosell, M., Villarroya, J., Iglesias, R., Gonzalez, F.J., Solanes, G., Villarroya, F. Endocrinology (2006) [Pubmed]
  18. Effects of fasting on muscle mitochondrial energetics and fatty acid metabolism in Ucp3(-/-) and wild-type mice. Bézaire, V., Hofmann, W., Kramer, J.K., Kozak, L.P., Harper, M.E. Am. J. Physiol. Endocrinol. Metab. (2001) [Pubmed]
  19. Dietary calcium regulates ROS production in aP2-agouti transgenic mice on high-fat/high-sucrose diets. Sun, X., Zemel, M.B. International journal of obesity (2005) (2006) [Pubmed]
  20. Activators of peroxisome proliferator-activated receptor-alpha induce the expression of the uncoupling protein-3 gene in skeletal muscle: a potential mechanism for the lipid intake-dependent activation of uncoupling protein-3 gene expression at birth. Brun, S., Carmona, M.C., Mampel, T., Viñas, O., Giralt, M., Iglesias, R., Villarroya, F. Diabetes (1999) [Pubmed]
  21. Uncoupling protein-3 mRNA up-regulation in C2C12 myotubes after etomoxir treatment. Cabrero, A., Alegret, M., Sánchez, R., Adzet, T., Laguna, J.C., Vázquez, M. Biochim. Biophys. Acta (2001) [Pubmed]
  22. 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]
  23. Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, beta3-adrenergic agonists, and leptin. Gong, D.W., He, Y., Karas, M., Reitman, M. J. Biol. Chem. (1997) [Pubmed]
  24. Uncoupling protein 3 transcription is regulated by peroxisome proliferator-activated receptor (alpha) in the adult rodent heart. Young, M.E., Patil, S., Ying, J., Depre, C., Ahuja, H.S., Shipley, G.L., Stepkowski, S.M., Davies, P.J., Taegtmeyer, H. FASEB J. (2001) [Pubmed]
  25. Insulin-induced up-regulated uncoupling protein-1 expression is mediated by insulin receptor substrate 1 through the phosphatidylinositol 3-kinase/Akt signaling pathway in fetal brown adipocytes. Valverde, A.M., Arribas, M., Mur, C., Navarro, P., Pons, S., Cassard-Doulcier, A.M., Kahn, C.R., Benito, M. J. Biol. Chem. (2003) [Pubmed]
  26. Energy metabolism and expression of uncoupling proteins 1, 2, and 3 after 21 days of recovery from intracerebroventricular mouse leptin in rats. Gullicksen, P.S., Flatt, W.P., Dean, R.G., Hartzell, D.L., Baile, C.A. Physiol. Behav. (2002) [Pubmed]
  27. Long-term effects of a fatty acid synthase inhibitor on obese mice: food intake, hypothalamic neuropeptides, and UCP3. Cha, S.H., Hu, Z., Lane, M.D. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  28. Energy metabolism of adipose tissue--physiological aspects and target in obesity treatment. Kopecký, J., Rossmeisl, M., Flachs, P., Brauner, P., Sponarová, J., Matejková, O., Prazák, T., Růzicková, J., Bardová, K., Kuda, O. Physiological research / Academia Scientiarum Bohemoslovaca. (2004) [Pubmed]
  29. Cloning of mouse uncoupling protein 3 cDNA and 5'-flanking region, and its genetic map. Yoshitomi, H., Yamazaki, K., Tanaka, I. Gene (1998) [Pubmed]
  30. 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]
  31. Downregulation of uncoupling protein 2 mRNA in white adipose tissue and uncoupling protein 3 mRNA in skeletal muscle during the early stages of leptin treatment. Combatsiaris, T.P., Charron, M.J. Diabetes (1999) [Pubmed]
  32. Structure and nucleotide polymorphisms in pig uncoupling protein 2 and 3 genes. Li, H., Li, Y., Zhao, X., Li, N., Wu, C. Anim. Biotechnol. (2005) [Pubmed]
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