, Volume 35, Issue 4, pp 421–425 | Cite as

Dietary fat-induced suppression of lipogenic enzymes in B/B rats during the development of diabetes



This study was designed to determine the level of inhibition of gene transcription by the reduction in insulin levels upon the onset of diabetes in spontaneously diabetic B/B rats and if reducing the level of polyunsaturated fatty acids (PUFA) in the diet will increase lipogenic enzyme activity. Control (eight animals per group) and spontaneously diabetic B/B male weanling rats (25 animals per group) were fed semipurified diets containing 20% (w/w) fat of either low (0.25) or high (1.0) polyunsaturated to saturated (P/S) fatty acid ratio. Rats were killed at the onset of diabetes [blood glucose level of ≅100 mg/dL (5.55 mM)] and as they became highly diabetic [blood glucose level of ≅400 mg/dL (22.22 mM)]. Total RNA was extracted from liver, and the relative amount of mRNA coding for fatty acid synthase (FAS), acetyl-CoA carboxylase, malic enzyme, pyruvate kinase, and phosphoenolpyruvate carboxykinase was determined. Liver enzyme activities were also measured. The mRNA levels for FAS, acetyl-CoA carboxylase, and malic enzyme decreased compared to control animals. The mRNA level for pyruvate kinase decreased at the onset of diabetes as compared to control animals. Feeding animals the low P/S diet treatment elevated the level of mRNA and lipogenic enzyme activity compared to animals fed the high P/S diet treatment, suggesting that the effect of PUFA on lipogenic enzymes is through a direct effect on gene expression.



acetyl-CoA carboxylase


fatty acid synthase


malic enzyme


phosphoenolpyruvate carboxykinase


polyunsaturated fatty acid


ratio of polyunsaturated to saturated fatty acid


a solution containing 0.3 M NaCl+0.03 M sodium citrate at pH 7.0


sodium dodecyl sulfate


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  1. 1.
    Back, D.W., Wilson, S.B., Morris, S.M. and Goodridge, A.G. (1986) Hormonal Regulation of Lipogenic Enzymes in Chick Embryo Hepatocytes in Culture, J. Biol. Chem. 261, 12555–12561.PubMedGoogle Scholar
  2. 2.
    Katsurada, A., Iritani, N., Fakuda, H., Matsurada, Y., Nishimoto, N., Noguchi, T., and Tanaka, T. (1990) Effects of Nutrients and Hormones on Transcriptional and Post Transcriptional Regulation of Acetyl CoA Carboxylase in Rat Liver, Eur. J. Biochem. 190, 435–441.PubMedCrossRefGoogle Scholar
  3. 3.
    McHugh, K.M., and Drake, R.L. (1989) Insulin-Mediated Regulation of Epididymal Fat Pad Malic Enzyme, Mol. Cell. Endocrinol. 62, 227–233.PubMedCrossRefGoogle Scholar
  4. 4.
    Pape, M.E., Lopez-Casillas, F., and Kim, K.H. (1988) Physiological Regulation of Acetyl CoA Carboxylase Gene Expression: Effects of Diet, Diabetes, and Lactation on Acetyl CoA Carboxylase mRNA, Arch. Biochem. Biophys. 267, 104–109.PubMedCrossRefGoogle Scholar
  5. 5.
    Warnotte, C., Gilon, P., Nenquin, M., and Henquin, J. (1994) Mechanisms of the Stimulation of Insulin Release by Saturated Fatty Acids. A Study of Palmitate Effects in Mouse β-Cells, Diabetes 43, 703–711.PubMedGoogle Scholar
  6. 6.
    Clandinin, M.T., Cheema, S., Field, C.J., Garg, M.L., Venkatraman, J., and Clandinin, T.R. (1991) Dietary Fat: Exogenous Determination of Membrane Structure and Cell Function, FASEB J. 5, 2761–2769.PubMedGoogle Scholar
  7. 7.
    Clandinin, M.T., Jumpsen, J., and Suh, M. (1994) Relationship Between Fatty Acid Accretion, Membrane Composition and Biologic Functions (rev.), J. Pediatrics 125, S25-S32.Google Scholar
  8. 8.
    Field, C.J., Ryan, E.A., Thomson, A.B.R., and Clandinin, M.T. (1988) Dietary Fat and the Diabetic State Alter Insulin Binding and the Fatty Acyl Composition of the Adipocyte Plasma Membrane, Biochem. J. 253, 417–424.PubMedGoogle Scholar
  9. 9.
    Blake, W.L., and Clarke, S.D. (1990) Suppression of Rat Hepatic Fatty Acid Synthase and S14 Gene Transcription by Dietary Polyunsaturated Fat, J. Nutr. 120, 1727–1729.PubMedGoogle Scholar
  10. 10.
    Clarke, S.D., Armstrong, M.K., and Jump, D.B. (1990) Dietary Polyunsaturated Fats Uniquely Suppress Rat Liver Fatty Acid Synthase and S14 mRNA Content, J. Nutr. 120, 225–231.PubMedGoogle Scholar
  11. 11.
    Clarke, S.D., and Jump, D.B. (1993) Regulation of Gene Transcription by Polyunsaturated Fatty Acids, Prog. Lipid Res. 32, 139–149.PubMedCrossRefGoogle Scholar
  12. 12.
    Jump, D.B., Clarke, S.D., MacDougald, O., and Thelen, A. (1993) Polyunsaturated Fatty Acids Inhibit S14 Gene Transcription in Rat Liver and Cultured Heaptocytes, Proc. Natl. Acad. Sci. USA 90, 8454–8458.PubMedCrossRefGoogle Scholar
  13. 13.
    Clarke, S.D., Armstrong, M.K., and Jump, D.B. (1990) Nutritional Control of Rat Liver Fatty Acid Synthase and S14 mRNA Abundance, J. Nutr. 120, 218–224.PubMedGoogle Scholar
  14. 14.
    Marliss, E.B., Nakhooda, A.F., Poussier, P., and Sima, A.A.F. (1982) The Diabetic Syndrome of the “BB” Wistar Rat: Possible Relevance to Type 1 (insulin-dependent) Diabetes in Man, Diabetologia 22, 225–232.PubMedCrossRefGoogle Scholar
  15. 15.
    Like, A.A., Appel, M.C., and Rossini, A.A. (1982) Autoantibodies in the BB/W Rat, Diabetes 31, 816–820.PubMedGoogle Scholar
  16. 16.
    Chomczynski, P., and Sacchi, N. (1987) Single-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate-Phenol-Chloroform Extraction, Anal. Biochem. 162, 156–159.PubMedCrossRefGoogle Scholar
  17. 17.
    Nepokroeff, C.M., Lakshman, M.R., and Porter, J.W. (1975) Fatty Acid Synthase from Rat Liver, Methods Enzymol. 35, 37–44.PubMedGoogle Scholar
  18. 18.
    Hsu, R.Y., and Lardy, H.A. (1969) l-Malate: NADP Oxidoreductase (decarboxylating), Methods Enzymol. 13, 230–235.Google Scholar
  19. 19.
    Inoue, H., and Lowenstein, J.M. (1975) Acetyl Coenzyme A Carboxylase from Rat Liver, EC Acetyl-CoA: Carbon Dioxide Ligase (ADP), Methods Enzymol. 35, 3–11.PubMedGoogle Scholar
  20. 20.
    Imamura, K., and Tanaka, T. (1982) Pyruvate Kinase Isozymes from Rat, Methods Enzymol. 90, 150–165.PubMedCrossRefGoogle Scholar
  21. 21.
    Petrescu, I., Brojan, O., Saied, M., Barzu, O., Schmidt, F., and Kuhnle, H.F. (1979) Determination of Phosphoenol Pyruvate Carboxykinase Activity with Deoxyguanosine 5′-Diphosphate as Nucleotide Substrate, Anal. Biochem. 96, 279–281.PubMedCrossRefGoogle Scholar
  22. 22.
    Witters, L.A., and Kemp, B.E. (1992) Insulin Activation of Acetyl CoA Carboxylase Accompanied by Inhibition of the 5′-AMP-Activated Protein Kinase, J. Biol. Chem. 267, 2864–2867.PubMedGoogle Scholar
  23. 23.
    Noguchi, T., Inoue, H., and Tanaka, T. (1985) The MI and M2 Type Isozymes of Rat Pyruvate Kinase Are Produced from the Same Gene by Alternative RNA Splicing, J. Biol. Chem. 260, 14393–14397.PubMedGoogle Scholar
  24. 24.
    Lamers, W.H., Hanson, R.W., and Meisner, H.M. (1982) cAMP Stimulates Transcription of the Gene for Cytosolic Phosphoenolpyruvate Carboxykinase in Rat Liver Nuclei, Proc. Natl. Acad. Sci. USA 79, 5137–5141.PubMedCrossRefGoogle Scholar
  25. 25.
    Gletsu, N., Dixon, W., and Clandinin, M.T. (1999) Insulin Receptor at the Nucleus Following a Glucose Meal Induces Dephosphorylation of a 30 KDa Transcription Factor and a Concomitant Increase in Malic Enzyme Gene Expression, J. Nutr. 129, 2154–2161.PubMedGoogle Scholar

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© AOCS Press 2000

Authors and Affiliations

  1. 1.Department of Agricultural, Food and Nutritional ScienceUniversity of Alberta, Nutrition and Metabolism Research GroupEdmontonCanada
  2. 2.Department of MedicineUniversity of Alberta, Nutrition and Metabolism Research GroupEdmontonCanada

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