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Gene Review

Ucp2  -  uncoupling protein 2 (mitochondrial,...

Rattus norvegicus

Synonyms: Mitochondrial uncoupling protein 2, Slc25a8, Solute carrier family 25 member 8, UCP 2
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Disease relevance of Ucp2


Psychiatry related information on Ucp2

  • By contrast, in the gastrocnemius muscle (a mixed fiber type muscle with a high capacity to shift between glucose and lipids as fuel substrate), mRNA expression of both UCP2 and UCP3 mRNA was found to be markedly up-regulated during food deprivation (when this tissue's thermogenesis is also decreased but its lipid fuel utilization is increased) [5].

High impact information on Ucp2

  • Here we show that leptin alters in pancreatic islets the mRNA of the genes encoding enzymes of free fatty acid metabolism and uncoupling protein-2 (UCP-2) [6].
  • Leptin overexpression increased UCP-2 mRNA by more than 10-fold in epididymal, retroperitoneal, and subcutaneous fat tissue of normal, but not of leptin-receptor-defective obese rats [6].
  • The hypothesis that fatty hepatocytes undergo cell cycle arrest due to (1) an inability to replenish ATP due to overexpressed uncoupling protein-2 (UCP-2) or (2) induction of growth inhibitor p21 leading to G1/S phase arrest was tested [7].
  • Steatotic livers showed 10-fold lower ATP levels due to upregulated UCP-2 throughout the time course after CCl4 administration, leading to sustained inhibition of cell division [7].
  • Exposure of neonatal cardiomyocytes and embryonic rat heart-derived H9c2 cells to fatty acids (palmitic and oleic acid) for 48 h strongly induced UCP-2 expression [8].

Chemical compound and disease context of Ucp2


Biological context of Ucp2

  • And it is possible that its site of action can be located in the energy-consuming exocytotic process of insulin secretory granules, and that the reduction of ATP production through increased UCP-2 reduces insulin exocytosis [14].
  • Taken together, these studies indicate a close association between fasting-induced changes in UCP2 and UCP3 gene expression with those of key regulators of lipid oxidation, and are hence consistent with the hypothesis that these UCP homologs may be involved in the regulation of lipid metabolism [15].
  • Skeletal muscle heterogeneity in fasting-induced upregulation of genes encoding UCP2, UCP3, PPARgamma and key enzymes of lipid oxidation [15].
  • To investigate whether fasting affects the expression of UCPs mRNA in brown adipose tissue (BAT) of bilateral ventromedial hypothalamus (VMH)-lesioned rats, we determined the gene expression of UCP1, UCP2 or UCP3 in BAT of VMH-lesioned rats and examined oxygen consumption in these rats under fed or 48-h fasted conditions [16].
  • As with autologous UCP2 mRNA, TZDs stimulated reporter gene expression directed by ucp2 sequences in transiently transfected L6 cells [17].

Anatomical context of Ucp2

  • The different expression patterns of genes for uncoupling proteins (UCPs) 1, 2 and 3 (ucp1, ucp2 and ucp3) were studied in interscapular brown adipose tissue (BAT) and in four white adipose tissue (WAT) depots (epididymal, inguinal, mesenteric and retroperitoneal) in male rats of different ages (18 days-12 months) [18].
  • PPAR-gamma overexpression selectively suppresses insulin secretory capacity in isolated pancreatic islets through induction of UCP-2 protein [14].
  • Although the expression of PPARalpha/RXRalpha leads to the induction of UCP2 mRNA and protein, this is not accompanied by reduced hyperpolarization of the mitochondrial membrane, indicating that under these conditions, increased UCP2 expression is insufficient for dissipation of the mitochondrial proton gradient [19].
  • It has been speculated that some of these long-term effects are mediated by members of the peroxisome proliferator-activated receptor (PPAR) family via an induction of uncoupling protein-2 (UCP2) [19].
  • Although UCP2 is known to be related to many functions such as the regulation of insulin secretion or the scavenging of the radicals, the role of UCP2 in the central nervous system remains unclear [20].

Associations of Ucp2 with chemical compounds

  • Within the context of this hypothesis, we have compared, from fed and fasted rats, changes in gene expression of skeletal muscle UCP2 and UCP3 with those of carnitine palmitoyltransferase I and medium-chain acyl-CoA dehydrogenase, two key enzymes regulating lipid flux across the mitochondrial beta-oxidation pathway [15].
  • Blockade of protein synthesis with cycloheximide as well as abrogation of mitogen-activated protein kinase (MAPK) activity with PD98059 or U0126 also prevented the TZD-induced increase in UCP2 mRNA [17].
  • Bisphenol A diglycidyl ether, a PPARy antagonist, concentration dependently inhibited the TZD-induced increase in UCP2 mRNA [17].
  • Glucose per se failed to affect UCP-2 mRNA [21].
  • Culture with aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside, an activator of AMP-activated protein kinase, decreased cellular triglycerides, increased postculture [1-(14)C] oleate oxidation, and increased UCP-2 mRNA [21].

Regulatory relationships of Ucp2


Other interactions of Ucp2

  • In BAT, there were high levels of expression of UCP1 and UCP3 mRNA, but no detectable levels of UCP2 mRNA [18].
  • In contrast to ucp1 and ucp3, ucp2 had a peak of expression at about 2 months, and lower expression at 3 months, suggesting different regulation and probably a different role for this UCP [18].
  • It has been reported that the insulin sensitizers, thiazolidinediones (TZDs), increase UCP2 mRNA levels and, more recently, that TZDs stimulate UCP2 reporter genes but that the sequences involved do not bind peroxisome proliferator-activated receptor gamma (PPARgamma) [17].
  • TZDs, however, did not increase the activation of MAPK, nor did its activation by other means (change of medium, insulin-like growth factor-1, insulin) increase UCP2 mRNA, indicating that phosphorylation is not limiting [17].
  • Enterostatin decreases postprandial pancreatic UCP2 mRNA levels and increases plasma insulin and amylin [22].

Analytical, diagnostic and therapeutic context of Ucp2


  1. Recruitment of mitochondrial uncoupling protein UCP2 after lipopolysaccharide induction. Růzicka, M., Skobisová, E., Dlasková, A., Santorová, J., Smolková, K., Spacek, T., Zácková, M., Modrianský, M., Jezek, P. Int. J. Biochem. Cell Biol. (2005) [Pubmed]
  2. Rat uncoupling protein 2 (UCP2): expression in obese ventromedial hypothalamus (VMH)-lesioned animals. Strobel, A., Combettes-Souverain, M., Doaré, L., Strosberg, A.D., Issad, T. Int. J. Obes. Relat. Metab. Disord. (1998) [Pubmed]
  3. Cardiac UCP2 expression and myocardial oxidative metabolism during acute septic shock in the rat. Roshon, M.J., Kline, J.A., Thornton, L.R., Watts, J.A. Shock (2003) [Pubmed]
  4. mRNA for pancreatic uncoupling protein 2 increases in two models of acute experimental pancreatitis in rats and mice. Segersvärd, R., Rippe, C., Duplantier, M., Herrington, M.K., Isaksson, B., Adrian, T.E., Erlanson-Albertsson, C., Permert, J. Cell Tissue Res. (2005) [Pubmed]
  5. Role of UCP homologues in skeletal muscles and brown adipose tissue: mediators of thermogenesis or regulators of lipids as fuel substrate? Samec, S., Seydoux, J., Dulloo, A.G. FASEB J. (1998) [Pubmed]
  6. Induction by leptin of uncoupling protein-2 and enzymes of fatty acid oxidation. Zhou, Y.T., Shimabukuro, M., Koyama, K., Lee, Y., Wang, M.Y., Trieu, F., Newgard, C.B., Unger, R.H. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  7. Nonalcoholic fatty liver sensitizes rats to carbon tetrachloride hepatotoxicity. Donthamsetty, S., Bhave, V.S., Mitra, M.S., Latendresse, J.R., Mehendale, H.M. Hepatology (2007) [Pubmed]
  8. Effects of fatty acids on uncoupling protein-2 expression in the rat heart. Van Der Lee, K.A., Willemsen, P.H., Van Der Vusse, G.J., Van Bilsen, M. FASEB J. (2000) [Pubmed]
  9. Enhancing effect of taurine on glucose response in UCP2-overexpressing beta cells. Lee, S.H., Sang-Hoon, L., Lee, H.Y., Hyun-Young, L., Kim, S.Y., So-Yeon, K., Lee, I.K., In-Kyu, L., Song, D.K., Dae-Kyu, S. Diabetes Res. Clin. Pract. (2004) [Pubmed]
  10. Interleukin-1beta swiftly down-regulates UCP-2 mRNA in beta-cells by mechanisms not directly coupled to toxicity. Li, L.X., Yoshikawa, H., Egeberg, K.W., Grill, V. Cytokine (2003) [Pubmed]
  11. UCP2-dependent proton leak in isolated mammalian mitochondria. Fink, B.D., Hong, Y.S., Mathahs, M.M., Scholz, T.D., Dillon, J.S., Sivitz, W.I. J. Biol. Chem. (2002) [Pubmed]
  12. Enhanced expression of uncoupling protein 2 gene in rat white adipose tissue and skeletal muscle following chronic treatment with thyroid hormone. Masaki, T., Yoshimatsu, H., Kakuma, T., Hidaka, S., Kurokawa, M., Sakata, T. FEBS Lett. (1997) [Pubmed]
  13. Regulation of UCP1, UCP2, and UCP3 mRNA expression in brown adipose tissue, white adipose tissue, and skeletal muscle in rats by estrogen. Pedersen, S.B., Bruun, J.M., Kristensen, K., Richelsen, B. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  14. PPAR-gamma overexpression selectively suppresses insulin secretory capacity in isolated pancreatic islets through induction of UCP-2 protein. Ito, E., Ozawa, S., Takahashi, K., Tanaka, T., Katsuta, H., Yamaguchi, S., Maruyama, M., Takizawa, M., Katahira, H., Yoshimoto, K., Nagamatsu, S., Ishida, H. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  15. Skeletal muscle heterogeneity in fasting-induced upregulation of genes encoding UCP2, UCP3, PPARgamma and key enzymes of lipid oxidation. Samec, S., Seydoux, J., Russell, A.P., Montani, J.P., Dulloo, A.G. Pflugers Arch. (2002) [Pubmed]
  16. Fasting increases gene expressions of uncoupling proteins and peroxisome proliferator-activated receptor-gamma in brown adipose tissue of ventromedial hypothalamus-lesioned rats. Kageyama, H., Osaka, T., Kageyama, A., Kawada, T., Hirano, T., Oka, J., Miura, M., Namba, Y., Ricquier, D., Shioda, S., Inoue, S. Life Sci. (2003) [Pubmed]
  17. Regulation of uncoupling protein-2 mRNA in L6 myotubules: I: Thiazolidinediones stimulate uncoupling protein-2 gene expression by a mechanism requiring ongoing protein synthesis and an active mitogen-activated protein kinase. López-Solache, I., Marie, V., Vignault, E., Camirand, A., Silva, J.E. Endocrine (2002) [Pubmed]
  18. Differential expression of genes for uncoupling proteins 1, 2 and 3 in brown and white adipose tissue depots during rat development. Oliver, P., Picó, C., Palou, A. Cell. Mol. Life Sci. (2001) [Pubmed]
  19. Peroxisome proliferator-activated receptor alpha (PPARalpha) potentiates, whereas PPARgamma attenuates, glucose-stimulated insulin secretion in pancreatic beta-cells. Ravnskjaer, K., Boergesen, M., Rubi, B., Larsen, J.K., Nielsen, T., Fridriksson, J., Maechler, P., Mandrup, S. Endocrinology (2005) [Pubmed]
  20. Uncoupling protein 2 influences dopamine secretion in PC12h cells. Yamada, S., Isojima, Y., Yamatodani, A., Nagai, K. J. Neurochem. (2003) [Pubmed]
  21. Induction of uncoupling protein 2 mRNA in beta-cells is stimulated by oxidation of fatty acids but not by nutrient oversupply. Li, L.X., Skorpen, F., Egeberg, K., Jørgensen, I.H., Grill, V. Endocrinology (2002) [Pubmed]
  22. Enterostatin decreases postprandial pancreatic UCP2 mRNA levels and increases plasma insulin and amylin. Arsenijevic, D., Gallmann, E., Moses, W., Lutz, T., Erlanson-Albertsson, C., Langhans, W. Am. J. Physiol. Endocrinol. Metab. (2005) [Pubmed]
  23. Pancreastatin, a chromogranin A-derived peptide, inhibits leptin and enhances UCP-2 expression in isolated rat adipocytes. González-Yanes, C., Sánchez-Margalet, V. Cell. Mol. Life Sci. (2003) [Pubmed]
  24. Difference in induction of uncoupling protein genes in adipose tissues between young and old rats during cold exposure. Yamashita, H., Sato, Y., Mori, N. FEBS Lett. (1999) [Pubmed]
  25. Polyunsaturated fatty acids stimulate hepatic UCP-2 expression via a PPARalpha-mediated pathway. Armstrong, M.B., Towle, H.C. Am. J. Physiol. Endocrinol. Metab. (2001) [Pubmed]
  26. Bacterial lipopolysaccharide induces uncoupling protein-2 expression in hepatocytes by a tumor necrosis factor-alpha-dependent mechanism. Cortez-Pinto, H., Yang, S.Q., Lin, H.Z., Costa, S., Hwang, C.S., Lane, M.D., Bagby, G., Diehl, A.M. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  27. Feeding Scallop Shell Powder Induces the Expression of Uncoupling Protein 1 (UCP1) in White Adipose Tissue of Rats. Liu, Y.C., Satoh, K., Hasegawa, Y. Biosci. Biotechnol. Biochem. (2006) [Pubmed]
  28. Localization of the mitochondrial uncoupling protein family in the rat inner ear. Kitahara, T., Li, H.S., Balaban, C.D. Hear. Res. (2004) [Pubmed]
  29. Decreased UCP2 mRNA expression in rat stomach following vagotomy: novel role for UCP2 as free radical scavenger in the stomach? Lindqvist, A., Mei, J., Sundler, F., Erlanson-Albertsson, C. Nutritional neuroscience. (2004) [Pubmed]
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