Skip to main content
Log in

Desaturase activities in rat model of insulin resistance induced by a sucrose-rich diet

  • Articles
  • Published:
Lipids

Abstract

A sucrose-rich diet, as compared with a similar starch diet, induces a time-dependent typical noninsulin-dependent diabetes syndrome characterized by insulin resistance in rats. Within the first 3 wk, there was glucose intolerance associated with hyperinsulinemia, hypertriglyceridemia, and high plasma FFA. In this study, we examined the effect of the sucrose-rich diet vs. the starch diet during short-(3 wk) and long-term treatment (6 mon) on hepatic Δ9, Δ6, and Δ5 desaturases. These enzymes modulate monounsaturated FA and PUFA biosynthesis, respectively. Sucrose feeding (3 wk) caused an initial hyperinsulinemia that was normalized within 6 mon. In the early period (3 wk), stearoyl-CoA desaturase-1 (SCD-1) mRNA and activity were decreased, whereas Δ6 desaturase mRNA abundance and Δ6 and Δ5 desaturase activities remained unchanged. After 6 mon of sucrose feeding, activities of the Δ9, Δ6, and Δ5 desaturases were each increased. The SCD-1 and Δ6 desaturase mRNA were also correspondingly higher. These increases were consistent with an increase in oleic acid, the 20∶4/18∶2 ratio, and 22∶4n−6 and 22∶5n−6 acids in liver and muscle lipids. On the other hand, the percentage of 22∶6n−3 acid was decreased. In conclusion, a sucrose-rich diet after 6 mon induces an increase in rat liver SCD-1 and Δ6 desaturase mRNA and enzymatic activities that are opposite to the changes reported in insulin-dependent diabetes mellitus. It appears that neither blood insulin levels nor insulin resistance is a factor affecting the Δ9, Δ6, and Δ5 desaturase changes in mRNA and activity found with the sucrose-rich diet.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

IDDM:

insulin-dependent diabetes mellitus

NIDDM:

noninsulin-dependent diabetes mellitus

PPAR:

peroxisome proliferator-activating receptor

SCD-1:

stearoyl-CoA desaturase-1

References

  1. Mc Garry, J.D. (2001) Dysregulation of Fatty Acid Metabolism in the Etiology of Type 2 Diabetes, Diabetes 51, 7–18.

    Google Scholar 

  2. Shulman, G.I. (2000) Cellular Mechanism of Insulin Resistance, J. Clin. Invest. 106, 171–176.

    Article  CAS  PubMed  Google Scholar 

  3. Shimomura, I., Matsuda, M., Hammer, R.E., Bashmakov, Y., Brown, M.S., and Goldstein, J.L. (2000), Decreased IRS-2 and Increased SREBPs Lead to Mixed Insulin Resistance and Sensitivity in Livers of Lipodystrophic and oblob Mice, Mol. Cell. 6, 77–86.

    Article  CAS  PubMed  Google Scholar 

  4. Elbein, S.C. (1997) The Genetics of Human Non-insulin-dependent (type 2) Diabetes Mellitus, J. Nutr. 127, 1891S-1896S.

    CAS  PubMed  Google Scholar 

  5. McIntosh, C.H.S., and Pederson, R.A. (1999) Non-insulin-dependent Animal Models of Diabetes Mellitus, in Experimental Models of Diabetes (McNeill, J.H., ed.), pp. 338–398, CRC Press, Boca Raton, FL.

    Google Scholar 

  6. Tobey, T.A., Mondon, C.E., Zavaroni, I., and Reaven, G.M. (1982) Mechanism of Insulin Resistance in Fructose-Fed Rats, Metabolism 31, 608–612.

    Article  CAS  PubMed  Google Scholar 

  7. Lombardo, Y.B., Chicco, A., Mocchiutti, N., Rodi, M., Nusemovich, B., and Gutman, R. (1983) Effects of Sucrose Diet on Insulin Secretion in vivo and in vitro and on Triglyceride Storage and Mobilization of the Hearts of Rats, Horm. Metab. Res. 15, 69–75.

    Article  CAS  PubMed  Google Scholar 

  8. Chicco, A., Basabe, J.C., Karabatas, L., Ferraris, N., Fortino, A., and Lombardo, Y.B. (2000) Troglitazone (CS-D45) Normalizes Hypertriglyceridemia and Restores the Altered Patterns of Glucose-Stimulated Insulin Secretion in Dyslipidemic Rats, Metabolism 49, 1346–1351.

    Article  CAS  PubMed  Google Scholar 

  9. Mercuri, O., Peluffo, R.O., and De Tomás, M.E. (1974) Effect of Different Diets on the Δ9 Desaturase Activity of Normal and Diabetic Rats, Biochim. Biophys. Acta 369, 264–268.

    CAS  PubMed  Google Scholar 

  10. Waters, K.M., and Ntambi, J.M. (1994) Insulin and Dietary Fructose Induce Stearoyl-CoA Desaturase 1 Gene Expression of Diabetic Mice, J. Biol. Chem. 269, 27773–27777.

    CAS  PubMed  Google Scholar 

  11. Sambrook, J., Fritsch, E.F., and Maniatis, T. (1989) Molecular Cloning A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.

    Google Scholar 

  12. Montes, M., Chicco, A., and Lombardo, Y.B. (2000) The Effect of Insulin on the Uptake and Metabolic Fate of Glucose in Isolated Perfused Hearts of Dyslipidemic Rats, J. Nutr. Biochem. 11, 30–37.

    Article  CAS  PubMed  Google Scholar 

  13. Laurell, S. (1966) A Method for Routine Determination of Plasma Triglycerides, Scand. J. Clin. Lab. Invest. 18, 668–672.

    CAS  PubMed  Google Scholar 

  14. Duncombe, W.B. (1963) The Colorimetric Microdetermination of Long-Chain Fatty Acids, Biochem. J. 88, 7–10.

    CAS  PubMed  Google Scholar 

  15. Bergmeyer, H.V. (1974) Methods for Determination of Metabolites, in Methods of Enzymatic Analysis, 2nd edn. (Bergmeyer, H.V., ed.) Academic Press, New York.

    Google Scholar 

  16. Herbert, V., Lau, K.S., Gottlieb, C.H., and Bleicher, S. (1965) Coated Charcoal Immunoassay of Insulin, J. Clin. Endocrinol. Metab. 25, 1375–1384.

    Article  CAS  PubMed  Google Scholar 

  17. Catalá, A., Nervi, A.M., and Brenner, R.R. (1975) Separation of a Protein Factor Necessary for the Oxidative Desaturation of Fatty Acids in the Rat, J. Biol. Chem. 250, 7481–7484.

    PubMed  Google Scholar 

  18. Lowry, O.H., Rosebrough, N.J., Farr, A.L., and Randall, R.J. (1951) Protein Measurement with the Folin Phenol Reagent, J. Biol. Chem. 193, 265–275.

    CAS  PubMed  Google Scholar 

  19. Folch, J., Lees, M., and Sloane Stanley, G.H. (1957) A Simple Method for the Isolation and Purification of Total Lipides from Animal Tissues, J. Biol. Chem. 226, 497–509.

    CAS  PubMed  Google Scholar 

  20. Chen, P.S., Toribara, T., and Warner, H. (1956) Microdetermination of Phosphorus, Anal. Chem. 28, 1756–1758.

    Article  CAS  Google Scholar 

  21. Lowry, R.R. (1968) Ferric Chloride Spray Detector for Cholesterol and Cholesterol Esters on Thin-Layer Chromatograms, J. Lipid Res. 9, 397.

    CAS  PubMed  Google Scholar 

  22. Soria, A., D'Alessandro, M.E., and Lombardo, Y.B. (2001) Duration of Feeding on a Sucrose-Rich Diet Determines Metabolic and Morphological Changes in Rat Adipocytes, J. Appl. Physiol. 91, 2109–2116.

    CAS  PubMed  Google Scholar 

  23. Lombardo, Y.B., Drago, S., Chicco, A., Fainstein-Day, P., Gutman, R., Gagliardino, J.J., and Gómez Dumm, C.L. (1996) Long-Term Administration of a Sucrose-Rich Diet to Normal Rats: Relationship Between Metabolic and Hormonal Profiles and Morphological Changes in the Endocrine Pancreas, Metabolism 45, 1527–1532.

    Article  CAS  PubMed  Google Scholar 

  24. Randle, P.J., Garland, P.B., Newsholme, E.A., and Hales, C.N. (1965) The Glucose Fatty Acid Cycle in Obesity and Maturity Onset Diabetes Mellitus, Ann. NY Acad. Sci. 131, 324–333.

    CAS  PubMed  Google Scholar 

  25. Henry, R.R. (1997) Thiazolidinediones, Endocrinol. Metab. Clin. North. Am. 26, 553–557.

    Article  CAS  PubMed  Google Scholar 

  26. Lee, M.K., Miles, P.D.G., Khoursherd, M., Gao, K.M., Moosa, A.R., and Olefsky, J.M. (1994) Metabolic Effects of Troglitazone on Fructose-Induced Insulin Resistance in the Rat, Diabetes 43, 1435–1439.

    CAS  PubMed  Google Scholar 

  27. Steppan, C.M., Bailey, S.T., Bhat, S., Brown, E.J., Banerjee, R.R., Wright, C.M., Datel, H.R., Ashima, R.S., and Lazar, M.A. (2001) The Hormone Resistin Links Obesity to Diabetes, Nature 409, 307–312.

    Article  CAS  PubMed  Google Scholar 

  28. Way, J.M., Görgün, C.Z., Tong, Q., Uysal, K.T., Brown, K.K., Harrington, W.W., Oliver, W.R., Jr., Willson, T.M., Kliewer, S.A., and Hottamisligil, G.S. (2001) Adipose Tissue Resistin Expression Is Severely Suppressed in Obesity and Stimulated by Peroxisome Proliferator-Activated Receptor γ Agonists, J. Biol. Chem. 276, 25651–25653.

    Article  CAS  PubMed  Google Scholar 

  29. Nagaev, I., and Smith, U. (2001) Insulin Resistance and Type 2 Diabetes Are Not Related to Resistin Expression in Human Fat Cells or Skeletal Muscle, Biochem. Biophys. Res. Commun. 285, 561–564.

    Article  CAS  PubMed  Google Scholar 

  30. Le Lay, S., Boucher, J., Rey, A., Castan-Laurell, I., Krief, S., Ferre, P., Valet, P., and Dugail, I. (2001) Decreased Resistin Expression in Mice with Different Sensitivities to a High-Fat Diet, Biochem. Biophys. Res. Commun. 289, 564–567.

    Article  PubMed  CAS  Google Scholar 

  31. Stumvoll, M., and Häring, H. (2002) The Peroxisome Proliferator-Activated Receptor-γ2 Pro 12Ala Polymorphism, Diabetes 51, 2341–2347.

    CAS  PubMed  Google Scholar 

  32. Brenner, R.R., Peluffo, R.O., Mercuri, O., and Restelli, M.A. (1968) Effect of Arachidonic Acid in the Alloxan-Diabetic Rat, Am. J. Physiol. 215, 63–70.

    CAS  PubMed  Google Scholar 

  33. Kim, Y.-C., Gómez, F.E., Fox, B.G., and Ntambi, J.M. (2000) Differential Regulation of the Stearoyl-CoA Desaturase Genes by Thiazolidinediones in 3T3-L1 Adipocytes, J. Lipid Res. 41, 1310–1316.

    CAS  PubMed  Google Scholar 

  34. Davies, G.F., McFie, P.J., Khandelwal, R.L., and Roesler, W.J. (2002) Unique Ability of Troglitazone to Up-regulate Peroxisome Proliferator-Activated Receptor γ Expression in Hepatocytes, J. Pharmacol. Exp. Ther. 300, 72–77.

    Article  CAS  PubMed  Google Scholar 

  35. Brenner, R.R., Bernasconi, A.M., and Garda, H.A. (2000) Effect of Experimental Diabetes on the Fatty Acid Composition, Molecular Species of Phosphatidylcholine and Physical Properties of Hepatic Microsomal Membrane, Prostaglandins Leukot. Essent. Fatty Acids 63, 167–176.

    Article  CAS  PubMed  Google Scholar 

  36. Rimoldi, O.J., Finarelli, G.S., and Brenner, R.R. (2001) Effects of Diabetes and Insulin on Hepatic Δ6 Desaturase Gene Expression, Biochem. Biophys. Res. Commun. 283, 323–326.

    Article  CAS  PubMed  Google Scholar 

  37. Brenner, R.R. (2003) Hormonal Modulation of Δ6 and Δ5 Desaturases: Case of Diabetes, Prostaglandins Leukot. Essent. Fatty Acids 68, 151–162.

    Article  CAS  PubMed  Google Scholar 

  38. D'Alessandro, M.E., Chicco, A., Karabatas, L., and Lombardo, Y.B. (2000) Role of Skeletal Muscle on Impaired Insulin Sensitivity in Rats Fed a Sucrose-Rich Diet: Effect of Moderate Levels of Dietary Fish Oil, J. Nutr. Biochem. 11, 273–280.

    Article  PubMed  Google Scholar 

  39. Storlien, L.H., Pan, D.A., Kriketos, A.D., O'Connor, J., Caterson, I.D., Cooney, G.J., Jenkins, A.E., and Baur, L.A. (1996) Skeletal Muscle Membrane Lipids and Insulin Resistance, Lipids 31 (Suppl.), 261–265.

    Google Scholar 

  40. Brenner, R.R., Ayala, S., and Garda, H.A. (2001) Effect of Dexamethasone on the Fatty Acid Composition of Total Liver Microsomal Lipids and Phosphatidylcholine Molecular Species, Lipids 36, 1337–1345.

    Article  CAS  PubMed  Google Scholar 

  41. Matsuzaka, T., Shimano, H., Yahagi, N., Amemiya-Kudo, M., Yoshikawa, T., Hasty, A.H., Tamura, Y., Osuga, J., Okazaki, H., Iizuka, Y., et al. (2002) Dual Regulation of Mouse Δ5 and Δ6 Desaturase Gene Expression by SREBP-1 and PPAR-α, J. Lipid Res. 43, 107–114.

    CAS  PubMed  Google Scholar 

  42. Nagai, Y., Nishio, Y., Nakamura, T., Maegawa, H., Kihkawa, R., and Kashiwagi, A. (2002) Amelioration of High-Fructose-Induced Metabolic Derangements by Activation of PPAR-α, Am. J. Physiol. 282, E1180-E1190.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rodolfo R. Brenner.

About this article

Cite this article

Brenner, R.R., Rimoldi, O.J., Lombardo, Y.B. et al. Desaturase activities in rat model of insulin resistance induced by a sucrose-rich diet. Lipids 38, 733–742 (2003). https://doi.org/10.1007/s11745-003-1121-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11745-003-1121-x

Keywords

Navigation