Journal of Bioenergetics and Biomembranes

, Volume 31, Issue 5, pp 493–506 | Cite as

Mitochondrial Uncoupling: Role of Uncoupling Protein Anion Carriers and Relationship to Thermogenesis and Weight Control “The Benefits of Losing Control”

Article

Abstract

Uncoupling proteins, a subgroup of the mitochondrial anion transporter superfamily, have beenidentified in prokaryotes, plants, and mammalian cells. Evolutionary conservation of thesemolecules reflects their importance as regulators of two critical mitochondrial functions, i.e.,ATP synthesis and the production of reactive oxygen species (ROS). Although the amino acidsequences of the three mammalian uncoupling proteins, UCP1, UCP2 and UCP3, are verysimilar, each homolog is the product of a unique gene and important differences have beendemonstrated in their tissue-specific expression and regulation. UCP1 and UCP3 appear to bekey regulators of energy expenditure, and hence, nonshivering thermogenesis, either in brownadipose tissue (UCP1) or skeletal muscle (UCP3). UCP2 is expressed more ubiquitously,although generally at low levels, in many tissues. There is conflicting evidence about itsimportance as a regulator of resting metabolic rate. However, evidence suggests that thishomolog might modulate the mitochondrial generation of ROS in some cell types, includingmacrophages and hepatocytes. While the induction of various uncoupling protein homologsprovides adaptive advantages, both to the organism (e.g., thermogenesis) and to individual cells(e.g., reduced ROS), increased uncoupling protein activity also increases cellular vulnerability tonecrosis by compromising the mitochondrial membrane potential. This narrow “risk—benefit”margin necessitates tight control of uncoupling protein activity in order to preserve cellularviability and much remains to be learned about the regulatory mechanisms involved.

Energy expenditure reactive oxygen species cellular viability apoptosis necrosis 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

REFERENCES

  1. Akerman, P., Cote, P., Yang, S. Q., McClain, C., Nelson, S., Bagby, G. J., and Diehl, A. M. (1992). Amer. J. Physiol. 263, G579-G585.Google Scholar
  2. Alvarez, R., DeAndres, J., Yubero, P., Vinas, O., Mampel, T., Iglesias, R., Giralt, J., and Villarroya, F. (1995). J. Biol. Chem. 270, 5666-5673.Google Scholar
  3. Aquila, H., Link, T. A., and Klingenberg, M. (1987). FEBS Lett. 212, 1-9.Google Scholar
  4. Bao, S., Kennedy, A., Wojciechowski, B., Wallace, P., Ganaway, E., and Garvey, W. T. (1998). Diabetes. 47, 1935-1940.Google Scholar
  5. Bernadi, P., Basso, E., Colonna, R., Costantini, P., Di Lisa, F., Eriksson, O., Fontaine, E., Forte, M., Ichas, F., Massari, S., Nicolli, A., Petronilli, V., and Scorrano, L. (1998). Biochim Biophys Acta 1365, 200-206.Google Scholar
  6. Bianco, A. C., and Silva, J. E. (1987). J. Clin. Invest. 79, 295-230.Google Scholar
  7. Bianco, A. C., and Silva, J. E. (1988). Amer. J. Physiol. 328, 207-215.Google Scholar
  8. Biengraeber, M., Echtay, K. S., and Klingenberg, M. (1998). Biochemistry 37, 3-8.Google Scholar
  9. Boss, O., Samec, S., Dulloo, A., Seydoux, J., Muzzin, P., and Giacobino, J.-P. (1997a). FEBS Lett. 412, 111-114.Google Scholar
  10. Boss, O., Samec, S., Paoloni-Giacobino, A., Rossier, C., Dulloo, A., J., S., Muzzin, P., and Giacobino, J.-P. (1997b). FEBS Lett. 408, 39-42.Google Scholar
  11. Boss, O., Bobbioni-Harsch, E., Assimacopoulos-Jeannet, F., Muzzin, P., Munger, R., Giacobino, J.-P., and Golay, A. (1998a). Lancet. 351, 1933.Google Scholar
  12. Boss, O., Muzzin, P., and Giacobino, J. P. (1998b). Eur. J. Endocrinol. 139, 1-9.Google Scholar
  13. Boss, O., Samec, S., Desplanches, D., Mayet, M. H., Seydoux, J., Muzzin, P., and Giacobino, J. P. (1998c). FASEB J. 12, 335-339.Google Scholar
  14. Boss, O., Samec, S., Kuhne, F., Bijlenga, P., Assimacopoulos-Jeannet, F., Seydoux, J., Giacobino, J. P., and Muzzin, P. (1998d). J. Biol. Chem. 273, 5-8.Google Scholar
  15. Bouillaud, F., Arechaga, I., Petit, P. X., Raimbault, S., Levi-Meyrueis, C., Casteilla, L., Laurent, M., Rial, E., and Ricquier, D. (1994). EMBO J. 13, 1990-1997.Google Scholar
  16. Bussquets, S., Sanchis, D., Alvarez, B., Ricquier, D., Lopez-Soriano, F.J., and Argiles, J. M. (1998). FEBS Lett. 440, 348-350.Google Scholar
  17. Campfield, L. A., Smith, F. J., and Burn, P. (1996). Hormone Metab. Res. 28, 619-632.Google Scholar
  18. Carmona, M. C., Valmaseda, A., Brun, S., Vinas, O., T., M., Iglesias, R., Giralt, M., and Villarroya, F. (1998). Biochem. Biophys. Res. Commun. 243, 224-228.Google Scholar
  19. Carretero, M. V., Torres, L., Latasa, U., Garci-Treviajano, E. R., Prieto, J., Mato, J. M., and Avila, M. A. (1998). FEBS Lett. 439, 55-58.Google Scholar
  20. Cassard-Doulcier, A. M., Gelly, C., Fox, N., Schrementi, J., Raimbault, S., Klaus, S., Forest, C., Bouillaud, F., and Ricquier, D. (1993). Mol. Endocrinol. 7, 497-506.Google Scholar
  21. Cassard-Doulcier, A. M., Larose, M., Matamala, J. C., Champigny, O., Bouillaud, F., and Ricquier, D. (1994). J. Biol. Chem. 269, 24335-24342.Google Scholar
  22. Casteilla, L., Blondel, O., Klaus, S., Raimbault, S., Diolez, P., Moreau, F., Bouillaud, F., and Ricquier, D. (1990). Proc. Natl. Acad. Sci. USA 87, 5124-5128.Google Scholar
  23. Champigny, O., and Ricquier, D. (1990). J. Nutr. 120, 1730-1736.Google Scholar
  24. Chavin, K., Yang, S. Q., Lin, H. Z., Chatham, J., Chacko, V. P., Hoek, J. B., Walajtyzs, Rode, E., Rashid, A., Chen, C.-H., Huang, C.-C., Lane, M. D., and Diehl, A. M. (1999). J. Biol. Chem., 274, 5692-5700.Google Scholar
  25. Chen, J., Gokhale, M., Li, Y., Trush, M. A., and Yager, J. D. (1998). Carcinogenesis 19, 2187-2193.Google Scholar
  26. Cortez-Pinto, H., Yang, S. Q., Lin, H. Z., Rashid, A., and Diehl, A. M. (1999). Gastroenterology 116, 1184-93.Google Scholar
  27. Cortez-Pinto, H., Yang, S. Q., Lin, H. Z., Costa, S., Hwang, C.-S., Lane, M. D., Bagby, G., and Diehl, A. M. (1998). Biochem. Biophys. Res. Commun. 251, 313-319.Google Scholar
  28. Emilsson, V., Summers, R. J., Hamilton, S., Liu, Y. L., and Cawthorne, M. A. (1998). Biochem. Biophys. Res. Commun. 252, 450-454.Google Scholar
  29. Factor, V. M., Kiss, A., Woitach, J. T., Wirth, P. J., and Thorgeirsson, S. S. (1998). J. Biol. Chem. 273, 15846-15853.Google Scholar
  30. Faggioni, R., Shigenaga, J., Moser, A., Feingold, K. R., and Grunfeld, C. (1998). Biochem. Biophys. Res. Commun. 244, 75-78.Google Scholar
  31. Fleury, C., Neverova, M., Collins, S., Raimbault, S., Champigny, O., Levi-Meyrueis, C., Bouillaud, R., Seldin, M. F., Surwit, R. S., Ricquier, D., and Warden, C. H. (1997). Nature Genet. 15, 269-272.Google Scholar
  32. Foellmi-Adams, L. A., Wyse, B. M., Herron, D., Nedergaard, J., and Kletzien, R. F. (1996). Biochem. Pharmacol. 52, 693-701.Google Scholar
  33. Gainsford, T., Willson, T. A., Metcalf, D., Handman, E., McFarlane, C., Ng, A., Nicola, N. A., Alexander, W. S., and Hilton, D. J. (1996). Proc. Natl. Acad. Sci. USA 93, 14564-14568.Google Scholar
  34. Giaraudo, S. Q., Kotz, C. M., Grace, M. K., Levine, A. S., and Billington, C. J. (1994). Amer. J. Physiol. 266, R1578-R1583.Google Scholar
  35. Gimeno, R. E., Dembski, M., Weng, X., Deng, N., Shyjan, A. W., Gimeno, C. J., Iris, F., Ellis, S. J., Woolf, E. A., and Tartagli, L. A. (1997). Diabetes 46, 900-906.Google Scholar
  36. Gong, D.-W., He, Y., Karas, M., and Reitman, M. (1997). J. Biol. Chem. 272, 24129-24132.Google Scholar
  37. Grasl-Kraupp, B., Bursch, W., Ruttkay-Nedecky, B., Wagner, A., Lauer, B., and Schulte-Hermann, R. (1994). Proc. Natl. Acad. Sci. USA 91, 9995-9999.Google Scholar
  38. Halestrap, A. P., and Davidson, A. M. (1990). Biochem. J. 268, 153-160.Google Scholar
  39. Hardie, D. G., and Carling, D. (1997).Eur. J. Biochem. 246, 259-273.Google Scholar
  40. Hodny, S., Kolarova, P., M., R., Horakova, M., Nibbelink, M., Penicaud, L., Casteilla, L., and Kopecky, J. (1998). FEBS Lett. 425, 185-190.Google Scholar
  41. Jezek, P., Orosz, D. E., Modriansky, M., and Garlid, K. D. (1994). J. Biol. Chem. 269, 26184-26190.Google Scholar
  42. Jezek, P., Modriansky, M., and Garlid, K. D. (1997). FEBS Lett. 408, 161-165.Google Scholar
  43. Jezek, P., Engstova, H., Zackova, M., Vercesi, A. E., Costa, A. D., Arruda, P., and Garlid, K. D. (1998). Biochim. Biophys. Acta 1365, 319-327.Google Scholar
  44. Kageyama, H., Suga, A., Kashiba, M., Oka, J., Osaka, T., Kashiwa, T., Hiraon, T., Nemoto, K., Namba, Y., Ricquier, D., Giacobino, J. P., and Inoue, S. (1998). FEBS Lett. 4, 450-453.Google Scholar
  45. Kelley, L. J., Vacario, P. P., Thompson, G. C., Candelore, M. R., Doebber, T. W., Ventre, J., Wu, M. S., Meurer, R., Forrest, M. J., Conner, M. W., Cascieri, M. A., and Moller, D. E. (1998). Endocrinology 139, 4920-4927.Google Scholar
  46. Kielar, D., Clark, J. S., Ciechanowicz, A., Kurzawski, G., Sulikowski, T., and Naruszewicz, M. (1998). Metabolism. 47, 844-847.Google Scholar
  47. Klannemark, M., Orho, M., and Groop, L. (1998). Eur. J. Endocrinol. 139, 217-223.Google Scholar
  48. Klaus, S., Ely, M., Encke, D., and Heldmaier, G. (1995). J. Cell. Sci. 108, 3171-3180.Google Scholar
  49. Klaus, S., Munzberg, H., Truloff, C., and Heldmaier, G. (1998). Amer. J. Physiol. 274, R287-R293.Google Scholar
  50. Klingenberg, M., Winkler, E., and Huang, S. (1995). Methods Enzymol. 260, 369-389.Google Scholar
  51. Knott, R. M., Trayburn, P., and Hesketh, J. E. (1992). Brit. J. Nutr. 68, 583-592.Google Scholar
  52. Komiya, T., et al.(1997). EMBO. J. 16, 4267-4275.Google Scholar
  53. Kopecky, J., Clarke, G., Enerback, S., Spiegelman, B., and Kozak, L. P. (1995). J. Clin. Invest. 96, 2914-2923.Google Scholar
  54. Korshunov, S. S., Korkina, O. V., Ruuge, E. K., Skulachev, V. P., and Starkov, A. A. (1998). FEBS Lett. 435, 215-218.Google Scholar
  55. Kowaltowski, A. J., Costa, A. D., and Vercesi, A. E. (1998). FEBS Lett. 425, 213-216.Google Scholar
  56. Kozak, L. P., Britton, J. H., Kozak, U. C., and Wells, J. M. (1988). J. Biol. Chem. 263, 12274-12277.Google Scholar
  57. Kren, B. T., Trembley, J. H., Krarewski, S., Behrens, T. W., Reed, J. C., and Steer, C. J. (1996). Cell Growth Diff. 7, 1633-1642.Google Scholar
  58. Kroemer, G., Dallaporta, B., and Resche-Rignon, M. (1998). Annu. Rev. Physiol. 60, 619-642.Google Scholar
  59. Kubota, T., Mori, H., Tamori, U., Okazawa, H., Kukuda, T., Midi, M., Ito, C., Fleury, C., Bouillaud, F., and Kasuga, M. (1998). J. Clin. Endocrinol Metab. 83, 2800-2804.Google Scholar
  60. Kushi, A., Sasai, H., Koizumi, H., Takeda, N., Yodoyama, M., and Nakamura, M. (1998). Proc. Natl. Acad. Sci. USA 95, 15659-15664.Google Scholar
  61. Kutoh, E., Boss, O., Levasseur, F., and Giacobino, J. P. (1998). Life Sci. 62, 445-451.Google Scholar
  62. Lanni, A., DeFelice, M., Lombardi, A., Moreno, M., Fleury, C., Ricquier, D., and Goglia, P. (1997). FEBS Lett. 418, 171-174.Google Scholar
  63. Larkin, S., Mull, E., Miao, W., Pittner, R., Albrandt, K., Moore, C., Young, A., Denaro, M., and Beaumont, K. (1997). Biochem. Biophys. Res. Commun. 240, 222-227.Google Scholar
  64. Larrouy, D., Laharrague, P., Carrera, G., Viguerie-Bascands, N., Levi-Meyrueis, C., Pecqeur, C., Nibbelink, M., Andre, M., Casteilla, L., and Ricquier, D. (1997). Biochem. Biophys. Res. Commun. 235, 760-764.Google Scholar
  65. Lee, F.-Y., Li, Y., Yang, E. K., Yang, S. Q., Lin, H. Z., Trush, M. A., Dannenberg, A. J., and Diehl, A. M. (1999). Amer. J. Physiol: Cell Physiol. 276, C386-C394.Google Scholar
  66. Lee, F. Y. J., Li, Y., Yang, S. Q., Trush, M., and Diehl, A. M. (1999). Hepatology, 29, 677-687.Google Scholar
  67. Lemasters, J. J. (1998). Gastroenterology 115, 783-786.Google Scholar
  68. Levine, J. A., Eberhardt, N. L., and Jensen, M. D. (1999). Science 283, 212-214.Google Scholar
  69. Liu, Q., Solanes, G., Vidal-Puig, A., Grujic, D., Flier, J. S., and Lowell, B. B. (1997). J. Biol. Chem. 2720, 25433-25436.Google Scholar
  70. Liu, Q., Bai, C., Chen, F., Wang, R., MacDonald, T., Gu, M., Zhang, Q., Morsy, M. A., and Caskey, C. T. (1998). Gene 207, 1-7.Google Scholar
  71. Loffreda, S., Yang, S. Q., Lin, H. Z., Bulkley, G., Bregman, M., Nobel, P., and Diehl, A. M. (1998). FASEB J. 12, 57-65.Google Scholar
  72. Marzo, I., Brenner, C., Zamzami, N., Susin, S. A., Beutner, G., Brdiczka, D., Remy, R., Xie, Z. H., Reed, J. C., and Kroemer, G. (1998a). J. Exp. Med. 187, 1261-1271.Google Scholar
  73. Marzo, I., Brenner, C., Zamzami, N., Jurgensmeier, J. M., Susin, S. A., Vierira, H. L. A., Prevost, M.-C., Xie, Z., Matsuyama, S., Reed, J. C., and Kroemer, G. (1998b). Science 281, 2027-2031.Google Scholar
  74. Masaki, T., Yoshimatsa, H., Kakuma, T., Hidaka, S., Kurokawa, M., and Sakata, T. (1997). FEBS Lett. 418, 323-326.Google Scholar
  75. Matamala, J. C., Gianotti, M., Pericas, J., Quevedo, S., Roca, P., Palou, A., and Garcia-Palmer, F. J. (1996). Biochem. J. 319, 529-534.Google Scholar
  76. Matsuda, J., Hosoda, K., Itoh, H., Son, C., Doi, K., Tanaka, T., Fukunaga, Y., Inoe, G., Nishimura, H., Yoshimasa, Y., Yamori, Y., and Nakao, K. (1997). FEBS Lett. 418, 200-204.Google Scholar
  77. Matsuda, J., Hosoda, K., Itoh, H., Son, C., Doi, K., Hanaoka, I., Inoe, G., Nishimura, H., Yoshimasa, Y., Yamori, Y., Odaka, H., and Nakao, K. (1998). Diabetes 47, 1809-1914.Google Scholar
  78. Merrick, B. A., He, C., Witcher, L. L., Patterson, R. M., Reid, J. J., Pence-Pawlowski, P. M., and Selkirk, J. K. (1996). Biochim. Biophys. Acta 1297, 57-68.Google Scholar
  79. Mignotte, B., and Vayssiere, J. L. (1998). Eur. J. Biochem. 252, 1-15.Google Scholar
  80. Millet, L., Vidal, H., Andreelli, F., Larrouy, D., Riou, J. P., Ricquier, D., Laville, M., and Langin, D. (1997). J. Clin. Invest. 100, 2665-2670.Google Scholar
  81. Millet, L., Vidal, H., Larrouy, D., Andreelli, F., Lavill, M., and Langin, D. (1998). Diabetologia 41, 829-832.Google Scholar
  82. Modriansky, M., Murdza-Inglis, D. L., Patel, H. V., Freeman, K., and Garlid, K. D. (1997). J. Biol. Chem. 272, 24759-24762.Google Scholar
  83. Moriscot, A., Rabcio, R., and Bianco, A. C. (1993). Amer. J. Physiol. 265, E81-E87.Google Scholar
  84. Mory, G., Bouillaud, F., Combes-George, M., and Ricquier, D. (1984). FEBS Lett. 166, 393-396.Google Scholar
  85. Muzzin, P., Revelli, J. P., Ricquier, D., Meier, M. K., Assimacoupoulos-Jeannet, F., and Giacobino, J. P. (1989). Biochem. J. 261, 721-721.Google Scholar
  86. Narita, M., Shimizu, S., Ito, T., Chittenden, T., Lutz, R. J., Matusuda, H., and Tsujimoto, Y. (1998). Proc. Natl. Acad. Sci. USA 95, 14681-14686.Google Scholar
  87. Negre-Salvayre, A., Hirtz, C., Carrera, G., Cazenave, R., Troly, M., Salvayre, R., Penicaud, L., and Casteilla, L. (1997). FASEB J. 11, 809-815.Google Scholar
  88. Nicholls, D. G., and Ferguson, S. J. (1992). Bioenergetics: An Introduction to the Chemiosmotic Theory(2nd ed.), Academic Press, New York.Google Scholar
  89. Nordfors, L., Hoffstedt, J., Nyberg, C., Thorne, A., Arner, P., Schalling, M., and Lonnqvist, F. (1998). Diabetologia 41, 935-939.Google Scholar
  90. Oberkofler, H., Liu, Y. M., Esterbauer, H., Hell, E., Drempler, F., and Patsch, W. (1998). Diabetologia 41, 940-946.Google Scholar
  91. Obregon, M. J., Pitamber, R., Jacobsson, A., Nedergaard, J., and Cannon, B. (1987). Biochem. Biophys. Res. Commun. 148, 9-14.Google Scholar
  92. Pastorino, J. G., Chen, S.-T., Tafani, M., Snyder, J. W., and Farber, J. L. (1998). J. Biol. Chem. 273, 7770-7775.Google Scholar
  93. Paulik, M. A., Buckholz, R. G., Lancaster, M. E., Dallas, W. S., Hull-Ryde, E. A., Weiel, J. E., and Lenhand, J. M. (1998). Pharmacol. Res. 15, 944-999.Google Scholar
  94. Polla, B. S., Kantengwa, S., Francois, D., Salvioli, S., Franceschi, C., Marsac, C., and Cossarizza, A. (1996). Proc. Natl. Acad. Sci. USA 93, 6458-6463.Google Scholar
  95. Puigserver, P., Vazquez, P., Bonet, M. I., Pico, C., and Palou, A. (1996). Biochem. J. 317, 827-833.Google Scholar
  96. Rashid, A., Wu, T.-C., Huang, C.-H., Chen, H.Z., Lin, H.Z., Yang, S.Q., Lee, F.Y.J., and Diehl, A. M. (1999). Hepatology 29, 1131-1138.Google Scholar
  97. Rehnmark, S., Nechad, M., Herron, D., B., C., and Nedergaard, J. (1990). J. Biol. Chem. 265, 16464-16471.Google Scholar
  98. Ricart, J., Egea, G., Izquierdo, J. M., San Martin, C., and Cuezva, J. M. (1997). Biochem. J. 324, 635-643.Google Scholar
  99. Ricquier, D. (1998). Biochem. Soc. Trans. 26, 120-123.Google Scholar
  100. Ricquier, D., Bouillaud, F., Toumelin, P., Mory, G., Bazin, R., J., A., and Penicaud, L.(1986). J. Biol. Chem. 261, 13905-13910.Google Scholar
  101. Samec, S., Seydoux, J., and Dulloo, A. G. (1998). FASEB J. 12, 715-724.Google Scholar
  102. Sanchis, D., Busquets, S., Ivarez, B., Ricquier, D., Lopez-Soriano, F. J.,and Argiles, J. M. (1998). FEBS Lett. 436, 415-418.Google Scholar
  103. Scarpace, P. J., and Matheny, M. (1998). Amer. J. Physiol. 275,E259-E264.Google Scholar
  104. Schleiff, E., and Turnbull, J. L. (1998). Biochemistry 37,13043-13051.Google Scholar
  105. Shimabukaro, M., Zhou, Y. t., Lee, Y., and Unger, R. H. (1997). Biochem. Biophys. Res. Commun. 237, 359-361.Google Scholar
  106. Shimizu, S., Eguchi, Y., Kamiike, W., Funahashi, Y., Mignon, A., Lacronique, V., Matsuda, H., and Tsujimoto, Y. (1998). Proc. Natl. Acad. Sci. USA 95,1455-1459.Google Scholar
  107. Shimokawa, T., Kato, M., Watanabe, Y., Hirayama, R., Kurosaki, E., Shikama, H., and Hashimoto, S. (1998). Bhichem. Biophys. Res. Commun. 25, 374-378.Google Scholar
  108. Siegrist-Kaiser, C. A., Pauli, V., Juge-Aubry, C. E., Boss, O., Pernin, A., Chin, W. W., Cusin, I., Rohner-Jeanrenaud, F., Burger, A. G., Zapf, J., and Meier, C. A. (1997). J. Clin. Invest. 100, 2858-2864.Google Scholar
  109. Silva, J. E., and Rabelo, R. (1997). Eur. J. Endocrinol. 136, 251-164.Google Scholar
  110. Simoneau, J. A., Kelley, D. E., Neverova, M., and Warden, C. H. (1998).FASEB J. 12, 1739-1745.Google Scholar
  111. Simonyan, R. A., and Skulachev, V. P. (1998). FEBS Lett. 436, 81-84.Google Scholar
  112. Skulachev, V. P. (1994). Biochemistry 59, 1433-1434.Google Scholar
  113. Skulachev, V. P. (1995). Mol. Biol. 29, 709-715.Google Scholar
  114. Skulachev, V. P. (1996a). FEBS Lett. 397, 7-10.Google Scholar
  115. Skulachev, V. P. (1996b). Quart. Rev. Biophys. 29, 169-202.Google Scholar
  116. Skulachev, V. P. (1997). Biosci. Rept. 17, 347-366.Google Scholar
  117. Stadler, J., Bentz, B. C., Harbrecht, B. G., Di silvio, M., Curran, R. D., Billiar, T. R., Hoffman, R. A., and Simmons, R. L. (1992). Ann. Surg. 216, 539-546.Google Scholar
  118. Strack, A. M., Bradbury, M. J., and Dallman, M. F. (1995a). Amer. J. Physiol. 268, R183-R191.Google Scholar
  119. Strack, A. M., Horsley, C. J., Sebastian, R. J., Akana, S. F., and Dallman, M. F. (1995b). Amer. J. Physiol. 268, R1209-R1216.Google Scholar
  120. Strobel, A., Combettes-Souverain, M., Doare, L., Strosberg, A. D., and Issad, R. (1998).Interm. J. Obesity Related Metab Disorders 22, 1121-1126.Google Scholar
  121. Stucki, J. W. (1980). Eur. J. Biochem. 109, 269-283.Google Scholar
  122. Takayama, S., Krajewski, S., Krajewska, M., Kiada, S., Zapata, J. M., Kochel, K., Knee, D., Scudiero, D., Tudor, G., Miller, G. J., Miyashita, T., Yamada, M., and Reed, J. C. (1998). Cancer Res. 58, 116-131.Google Scholar
  123. Tartaglia, L. A., Dembski, M., Weng, X., Deng, N., Culpepper, J., Devos, R., Rchards, G. J., Campfield, L. A., Clark, F. T., Deeds, J., et al.(1995).Cell 83(7), 1263-1271.Google Scholar
  124. Teruel, T., Valverde, A. M., Navarro, P., Benito, M., and Lorenzo, M. (1998). J. Cell Physiol. 176, 99-109.Google Scholar
  125. Tsuboyama-Kasaoka, N., Tsunoda, N., Maruyama, K., Takahashi, M., Kim, H., Ikemoto, S., and Ezaki, O. (1998). Biochem. Biophys. Res. Commun. 274, 498-503.Google Scholar
  126. Urhammer, S. A., Dalgaard, L. T., Sorensen, T. I., Tybjaerg-Hanse, A., Echwald, S. M., Andersen, T., Clausen, J. O., and Pedersen, O. (1998). Diabetologia 41, 241-244.Google Scholar
  127. Walder, K., Norman, R. A., Hanson, R. L., Schrauwen, P., Neverova, M., Jenkinson, C. P., Easlick, J., Warden, C. H., Pecqueur, C., Raimbault, S., Ricquier, D., Silver, M. H. K., Shuldiner, A. R., Solanes, G., Lowell, B. B., Chung, W. K., Leibel, R. L., Pratley, R., and Ravussin, E. (1998). Human Mol. Genet. 7, 1431-1435.Google Scholar
  128. Wiegle, D. S., Selfridge, L. I., Schwartz, M. W., Seeley, R. J., Cummings, D. E., Havel, P. J., Kuijper, J. L., and BeltrandelRio, H. (1998). Diabetes 47, 298-302.Google Scholar
  129. Wiesinger, H., Klaus, S., Heldmaier, G., Champigny, O., and Ricquier, D. (1990). Can. J. Physiol. Pharmacol. 68, 195-200.Google Scholar
  130. Winkler, E., Wachler, E., and Klingenberg, M. (1997). Biochemistry 36,148-155.Google Scholar
  131. Wojtczak, L., and Schonfeld, P., (1993). Biochim. Biophys. Acta 1183, 41-57.Google Scholar
  132. Yamada, M., Hashida, T., Shibusawa, N., Iwasaki, T., Murakami, M., Monden, T., Satoh, T., and Mori, M. (1998). FEBS Lett. 432, 65-69.Google Scholar
  133. Yoshitomi, H., Yamazaki, K., Abe, S., and Tanaka, I. (1998). Biochem. Biophys. Res. Commun. 253, 85-91.Google Scholar
  134. Yubero, P., Barbera, M. J., Alvarez, R., Vinal, O., Mampel, T., Iglesias, R., Villarroya, F.,and Giralt, M. (1998). Mol. Endocrinol. 12, 1023-1037.Google Scholar
  135. Zhou, Y. T., Shimabukuro, M., Koyama, K., Lee, Y., Wang, M. Y., Trieu, F., Newgard, C. B., and Unger, R. H. (1997). Proc. Natl. Acad. Sci. USA 94,6386-6390.Google Scholar

Copyright information

© Plenum Publishing Corporation 1999

Authors and Affiliations

  1. 1.Departments of MedicineThe Johns Hopkins UniversityBaltimore
  2. 2.Departments of PathologyThomas Jefferson UniversityPhiladelphia

Personalised recommendations