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Rat Models of the Metabolic Syndrome

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Renal Disease

Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 86))

Abstract

For some diseases, a line of causality exists in which a given antecedent elicits a particular disorder, which can be treated by interrupting a specific pathway of events. Most biomedical scientists have uncritically adopted the “line-of-causality” metaphor, and have therefore selected for study animal models of disease in which this metaphor by design must work because the models are chosen accordingly. Although peer review rewards the use of such models, and research with linear models of disease is often intellectually satisfying, it is doubtful that such an approach in the end will lead to breakthroughs for the treatment of the major diseases facing humankind today, such as cancer and cardiovascular disease.

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References

  1. Reaven, G. M. (1988) Role of insulin resistance in human disease. Diabetes 37, 1595–1607.

    Article  PubMed  CAS  Google Scholar 

  2. Rocchini, A. P. (1995) Insulin resistance, obesity and hypertension. Am. J. Nutr. 125, 1718S–1724S.

    CAS  Google Scholar 

  3. Vega, G. L. (2001) Obesity, the metabolic syndrome, and cardiovascular disease. Am. Heart J. 142, 1108–1116.

    Article  PubMed  CAS  Google Scholar 

  4. Isomaa, B., Almgren, P., Tuomi, T., Forsen, B., Lahti, K., Nissen, M., et al. (2001) Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 24, 683–689.

    Article  PubMed  CAS  Google Scholar 

  5. Marks, J. B. and Raskin, P. (1988) Nephropathy and hypertension in diabetes. Med. Clin. N Am. 82, 877–907.

    Article  Google Scholar 

  6. Sowers, J. R. and Epstein, M. (1995) Diabetes mellitus and associated hypertension, vascular disease and nephropathy. An update. Hypertension 26, 869–879.

    PubMed  CAS  Google Scholar 

  7. Zucker, L. M. and Zucker, T. F. (1961) Fatty, a new mutation in the rats. J. Hered. 52, 275–287.

    Google Scholar 

  8. Chua, S. C., Jr., White, D. W., Wu-Peng, X. S., Liu, S. M., Okada, N., Kershaw, E. E., et al. (1996) Phenotype of fatty due to Gln269Pro mutation in the leptin receptor (Lepr). Diabetes 45, 1141–1143.

    Article  PubMed  CAS  Google Scholar 

  9. White, D. W., Wang, Y., Chua, S. C., Jr., Morgenstern, J. P., Leibel, R. L., Baumann, H., et al. (1997) Constitutive and impaired signaling of leptin receptors containing the Gln → Pro extracellular domain fatty mutation. Proc. Natl. Acad. Sci. USA 94, 10657–10662.

    Article  PubMed  CAS  Google Scholar 

  10. Clark, J. B., Palmer, C. J., and Shaw, W. N. (1983) The diabetic Zucker fatty rat. Proc. Soc. Exp. Biol. Med. 173, 68–75.

    PubMed  CAS  Google Scholar 

  11. Peterson, R. G., Shaw, W. N., Neel, M.-A., Little, L. A., and Eichberg, J. (1990) Zucker diabetic fatty rats as a model for non-insulin-dependent diabetes mellitus. ILAR News 32, 16–19.

    Google Scholar 

  12. Peterson, R. G. (2000) The Zucker diabetic fatty (ZDF) rat, in Animal Models of Diabetes: A Primer (Sima, A. A. F. and Shafrir, E., eds.), Taylor and Francis, London, UK, pp. 109–128.

    Google Scholar 

  13. Okamoto, K. and Aoki, K. (1963) Development of a strain of spontaneously hypertensive rats. Jpn. Circ. J. 27, 282–293.

    PubMed  CAS  Google Scholar 

  14. Pinto, Y. M., Paul, M., and Ganten, D. (1998) Lessons from rat models of hypertension: from Goldblatt to genetic engineering. Cardiovas. Res. 39, 77–88.

    Article  CAS  Google Scholar 

  15. Yamori, Y., Tomimoto, K., Ooshima, A., Hazama, F., and Okamoto, K. (1974) Proceedings: developmental course of hypertension in the SHR-substrains susceptible to hypertensive cerebrovascular lesions. Jpn. Heart J. 15, 209–210.

    PubMed  CAS  Google Scholar 

  16. Koletsky, S. (1972) New type of spontaneously hypertensive rats with hyperlipemia and endocrine gland defects, in Spontaneous Hypertension: Its Pathogenesis and Complications (Okamoto, K., ed.), Igaku Shoin Ltd., Tokyo, Japan, pp. 194–197.

    Google Scholar 

  17. Takaya, K., Ogawa, Y., Hiraoka, J., Hosoda, K., Yamori, Y., Nakao, K., et al. (1996) Nonsense mutation of leptin receptor in the obese spontaneously hypertensive Koletsky rat. Nat. Genet. 14, 130–131.

    Article  PubMed  CAS  Google Scholar 

  18. Koletsky, R. J., Friedman, J. E., and Ernsberger, P. (2000) The obese spontaneously hypertensive rats (SHROB, Koletsky rats): A model of metabolic syndrome X, in Animal Models of Diabetes: A Primer (Sima, A. A. F. and Shafrir, E., eds.), Taylor and Francis, London, UK, pp. 109–128.

    Google Scholar 

  19. McCune, S. A., Baker, P. B., and Stills, H. F. Jr. (1990) SHHF/Mcc-cp rat: model of obesity, non-insulin-dependent diabetes, and congestive heart failure. ILAR News 32, 23–27.

    Google Scholar 

  20. Tofovic, S. P., Kusaka, H., Kost, C. K. Jr., and Bastacky, S. (2000) Renal function and structure in diabetic, hypertensive, obese, ZDFx SHHF-hybrid rats. Renal Fail. 22, 387–406.

    Article  CAS  Google Scholar 

  21. Yusuf, S., Sleight, P., Pogre, J., Bosch, J., Davies, R., and Dagenais, G. (2000) Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N. Engl. J. Med. 342, 145–153.

    Article  PubMed  CAS  Google Scholar 

  22. Tofovic, S. P., Kusaka, H., Jackson, E. K., and Bastacky, S. I. (1999) Renal function and structure in obese ZDFxSHHF (hybrid)fa/facp rats treated with caffeine or enalapril. J. Am. Soc. Nephrol. 10, 672A.

    Google Scholar 

  23. Kost, K. C., Jr., Bastacky, S. I., Jackson, E. K., and Tofovic, S. P. (2001) Renoprotective effects of angiotensin converting enzyme inhibition in an animal model of renal disease characterized by multiple risk factors. J. Am. Soc. Nephrol. 12, 839A.

    Google Scholar 

  24. Dubey, R. K. and Jackson, E. K. (2001) Cardiovascular protective effects of 17β-estradiol metabolites. J. Appl. Physiol. 91, 1868–1883.

    PubMed  CAS  Google Scholar 

  25. Tofovic, S. P., Dubey, R. K., and Jackson, E. K. (2001) 2-Hydroxyestradiol attenuates the development of obesity, metabolic syndrome, and vascular and renal dysfunction in obese ZSF1 rats. J. Pharmacol. Exp. Therap. 299, 973–977.

    CAS  Google Scholar 

  26. Planche, E., Joliff, M., de Gasquet P., and Leliepvre X. (1983) Evidence of a defect in energy expenditure in 7-day-old Zucker rat (fa/fa). Am. J. Physiol. 245, E107–E113.

    PubMed  CAS  Google Scholar 

  27. Meister, B. (2000) Control of food intake via leptin receptors in the hypothalamus. Vitam. Horm. 59, 265–304.

    Article  PubMed  CAS  Google Scholar 

  28. Dulloo, A. G. and Miller, D. S. (1987) Reversal of obesity in the genetically obese fa/fa Zucker rat with ephedrine/methylxanthines thermogenic mixture. J. Nutr. 117, 383–389.

    PubMed  CAS  Google Scholar 

  29. Tofovic, S. P., Kost, C. Jr., Jackson, E. K., and Bastacky, S. I. (2002) Long-term caffeine consumption exacerbates renal failure in obese, diabetic, ZSF1 (fa/fa cp) rats. Kidney Int. 61, 1433–1444.

    Article  PubMed  CAS  Google Scholar 

  30. Tofovic, S. P., Kusaka, H., Jackson E. K., and Bastacky, S. I. (2001) Renal and metabolic effects of caffeine in obese (fa/fa cp), diabetic, hypertensive, ZSF1 rats. Renal Failure 23, 159–173.

    Article  PubMed  CAS  Google Scholar 

  31. Vora, J. P., Zimsen, S. M., Houghton, D. C., and Anderson, S. (1996) Evolution of metabolic and renal changes in the ZDF/Drt-fa rat model of type II diabetes. J. Am. Soc. Nephrol. 7, 113–117.

    PubMed  CAS  Google Scholar 

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© 2003 Humana Press Inc., Totowa, NJ

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Tofovic, S.P., Jackson, E.K. (2003). Rat Models of the Metabolic Syndrome. In: Goligorsky, M.S. (eds) Renal Disease. Methods in Molecular Medicine™, vol 86. Humana Press. https://doi.org/10.1385/1-59259-392-5:29

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  • DOI: https://doi.org/10.1385/1-59259-392-5:29

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-134-9

  • Online ISBN: 978-1-59259-392-7

  • eBook Packages: Springer Protocols

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