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Effect of sucrose and saturated-fat diets on mRNA levels of genes limiting muscle fatty acid and glucose supply in rats

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Lipids

Abstract

In this study, we examined whether the increased availability of lipids in blood resulting from two types of diet manipulation regulated metabolic gene expression in the skeletal muscle of rats. Feeding for 4 wk on an isocaloric-sucrose or a hypercaloric-fat diet increased plasma TAG in the fed condition by increments of 70 and 40%, respectively, and increased fasting insulinemia (approximately 3-fold) compared with a starch diet. The fat diet impaired glucose tolerance and caused obesity, whereas sucrose-fed rats maintained their normal weight. We analyzed the expression of genes that regulate the exogenous FA supply (LPL, FAT/CD36, FATP1), synthesis (ACC1), glucose (GLUT4, GLUT1, HK2, GRAT1, glycogen phosphorylase) or glycerol (glycerol kinase) provision, or substrate choice for oxidation (PDK4) in gastrocnemius and soleus muscles at the end of the glucose tolerance test. LPL, FAT/CD36, FATP1, PDK4, and GLUT4 mRNA as well as glycogen phosphorylase and glycerol kinase activity levels in both muscles were unchanged by the diets. Increased mRNA levels of GLUT1 (1.6- and 2.6-fold, respectively) and GFAT1 (about 1.7-fold) in gastrocnemius, and of ACC1 (about 1.5-fold) in soleus, were found in both the sucrose and fat groups. In the fat group, HK2 mRNA was also higher (1.8-fold) in the gastrocnemius. Both sucrose and saturated-fat diets prompted hyperinsulinemia and hyperlipemia in rats. These metabolic disturbances did not alter the expression of LPL, FAT/CD36, FATP1, PDK4, and GLUT4 genes or glycogen phosphorylase and glycerol kinase activity levels in either analyzed muscle. Instead, they were linked to the coordinated upregulation in gastrocnemius of genes that govern glucose uptake and the hexosamine pathway, namely, GLUT1 and GFAT1, which might contribute to insulin resistance.

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Abbreviations

ACC1:

acetyl-Co carboxylase 1

CT:

threshold cycle

FAT/CD36:

fatty acid translocase

FATP1:

fatty acid transport protein 1

GFAT1:

glutamine: fructose-6-phosphate amidotransferase 1

GLUT` and GLUT4:

glucose transporters

HK2:

hexokinase 2

II30 :

insulinogenic index after 30 min

LPL:

lipoprotein lipase

PDK4:

pyruvate dehydrogenase kinase, isoenzyme 4

QUICKI:

quantitative insulin sensitivity check index

RPLP0:

ribosomal protein large, P0

UDP-GlcNAc:

uridine diphosphate-N-acetylglucosamine

References

  1. Fried, S.K., and Rao, S.P. (2003) Sugars, Hypertriglyceridemia, and Cardiovascular Disease, Am. J. Clin. Nutr. 78, 873S-880S.

    PubMed  CAS  Google Scholar 

  2. Hu, F.B., van Dam, R.M., and Liu, S. (2001) Diet and Risk of Type II Diabetes: The Role of Types of Fat and Carbohydrate, Diabetologia 44, 805–817.

    Article  PubMed  CAS  Google Scholar 

  3. Kim, J.Y., Nolte, L.A., Hansen, P.A., Han, D.H., Kawanaka, K., and Holloszy, J.O. (1999) Insulin Resistance of Muscle Glucose Transport in Male and Female Rats Fed a High-Sucrose Diet, Am. J. Physiol. 276, R665-R672.

    PubMed  CAS  Google Scholar 

  4. Commerford, S.R., Bizeau, M.E., McRae, H., Jampolis, A., Thresher, J.S., and Pagliassotti, M.J. (2001) Hyperglycemia Compensates for Diet-Induced Insulin Resistance in Liver and Skeletal Muscle of Rats, Am. J. Physiol. Regul. Integr. Comp. Physiol. 281, R1380-R1389.

    PubMed  CAS  Google Scholar 

  5. Santure, M., Pitre, M., Marette, A., Deshaies, Y., Lemieux, c., Lariviere, R., Nadeau, A., and Bachelard, H. (2002) Induction of Insulin Resistance by High-Sucrose Feeding Does Not Raise Mean Arterial Blood Pressure but Impairs Haemodynamic Responses to Insulin in Rats, Br. J. Pharmacol. 137, 185–196.

    Article  PubMed  CAS  Google Scholar 

  6. Marotta, M., Ferrer-Martínez, A., Parnau, J., Turini, M., Macé, K., and Gómez Foix, A.M. (2004) Fiber-Type and Fatty Acid Composition-Dependent Effects of High-Fat Diets on Rat Muscle Triacyglyceride and FATP-1 Content, Metabolism 53, 1032–1036.

    Article  PubMed  CAS  Google Scholar 

  7. Jocker, B.M., Cline, G.W., Barucci, N., and Shulman, G.I. (1999) Differential Effects of Safflower Oil Versus Fish Oil Feeding on Insulin-Stimulated Glycogen Synthesis, Glycolysis, and Pyruvate Dehydrogenase Flux in Skeletal Muscle, Diabetes 48, 134–140.

    Google Scholar 

  8. Storlien, L.H., Jenkins, A.B., Chisholm, D.J., Pascoe, W.S., Khouri, S., and Kraegen, E.W. (1991) Influence of Dietary Fat Composition on Development of Insulin Resistance in Rats. Relationship to Muscle Triglyceride and ω-3 Fatty Acids in Muscle Phospholipids, Diabetes 40, 280–289.

    PubMed  CAS  Google Scholar 

  9. Wright, D.W., Hansen, R.I., Mondon, C.E., and Reaven, G.M. (1983) Sucrose-Induced Insulin Resistance in the Rat: Modulation by Exercise and Diet, Am. J. Clin. Nutr. 38, 879–883.

    PubMed  CAS  Google Scholar 

  10. Gutman, R.A., Basilico, M.Z., Bernal, A., Chicco, A., and Lombardo, Y.B. (1987) Long-Term Hypertriglyceridemia and Glucose Intolerance in Rats Fed Chronically an Isocaloric Sucroserich Diet, Metabolism 36, 1013–1020.

    Article  PubMed  CAS  Google Scholar 

  11. Chicco, A., D'Alessandro, M.E., Karabatas, L., Pastorale, C., Basabe, J.C., and Lombardo, Y.B. (2003) Muscle Lipid Metabolism and Insulin Secretion Are Altered in Insulin-Resistant Rats Fed a High Sucrose Diet, J. Nutr. 133, 127–133.

    PubMed  CAS  Google Scholar 

  12. Sebokova, E., Klimes, I., Gasperikova, D., Bohov, P., Langer, P., Lavau, M., and Clandinin, M.T. (1996) Regulation of Gene Expression for Lipogenic Enzymes in the Liver and Adipose Tissue of Hereditary Hypertriglyceridemic, Insulin-Resistant Rats: Effect of Dietary Sucrose and Marine Fish Oil, Biochim. Biophys. Acta 1303, 56–62.

    PubMed  CAS  Google Scholar 

  13. Thresher, J.S., Podolin, D.A., Wei, Y., Mazzeo, R.S., and Pagliassotti, M.J. (2000) Comparison of the Effects of Sucrose and Fructose on Insulin Action and Glucose Tolerance, Am. J. Physiol. Regul. Integr. Comp. Physiol. 279, 1334–1340.

    Google Scholar 

  14. Lichtenstein, A.H., and Schwab, U.S. (2000) Relationship of Dietary Fat to Glucose Metabolism, Atherosclerosis 150, 227–243.

    Article  PubMed  CAS  Google Scholar 

  15. Basciano, H., Federico, L., and Adeli, K. (2005) Fructose, Insulin Resistance, and Metabolic Dyslipidemia, Nutr. Metab. (London) 21, 5.

    Article  CAS  Google Scholar 

  16. Sanders, T.A. (2003) Dietary Fat and Postprandial Lipids, Curr. Atheroscler. Rep. 5, 445–451.

    PubMed  Google Scholar 

  17. Han, D.H., Hansen, P.A., Host, H.H., and Holloszy J.O. (1997) Insulin Resistance of Muscle Glucose Transport in Rats Fed a High-Fat Diet: A Reevaluation, Diabetes 46, 1761–1767.

    PubMed  CAS  Google Scholar 

  18. Kahn, B.B. (1994) Dietary Regulation of Glucose Transporter Gene Expression: Tissue Specific Effects in Adipose Cells and Muscle, J. Nutr. 124, 1289S-1295S.

    PubMed  CAS  Google Scholar 

  19. Cameron-Smith, D., Burke, L.M., Angus, D.J., Tunstall, R.J., Cox, G.R., Bonen, A., Hawley, J.A., and Hargreaves M. (2003) A Short-Term, High-Fat Diet Up-regulates Lipid Metabolism and Gene Expression in Human Skeletal Muscle, Am. J. Clin. Nutr. 77, 313–318.

    PubMed  CAS  Google Scholar 

  20. Kim, J.K., Fillmore, J.J., Chen, Y., Yu, C., Moore, I.K., Pypaert, M., Lutz, E.P., Kako, Y., Velez-Carrasco, W., Goldberg, I.J. et al. (2001) Tissue-Specific Overexpression of Lipoprotein Lipase Causes Tissue-Specific Insulin Resistance, Proc. Natl. Acad. Sci. USA 98, 7522–7527.

    Article  PubMed  CAS  Google Scholar 

  21. Coburn, C.T., Knapp, F.F., Febbraio M., Beets, A.L., Silverstein, R.L., and Abumrad, N.A. (2000) Defective Uptake and Utilization of Long Chain Fatty Acids in Muscle and Adipose Tissues of CD36 Knockout Mice, J. Biol. Chem. 275, 32523–32529.

    Article  PubMed  CAS  Google Scholar 

  22. Ibrahimi, A., Bonen, A., Blinn, W.D., Hajri, T., Li, X., Zhong, K., Cameron, R., and Abumrad, N.A. (1999) Muscle-Specific Overexpression of FAT/CD36 Enhances Fatty Acid Oxidation by Contracting Muscle, Reduces Plasma Triglycerides and Fatty Acids, and Increases Plasma Glucose and Insulin, J. Biol. Chem. 274, 26761–26766.

    Article  PubMed  CAS  Google Scholar 

  23. Kim, J.K., Gimeno, R.E., Higashimori, T., Kim, H.J., Choi, H., Punreddy, S., Mozell, R.L., Tan, G., Stricker-Krongrad, A., Hirsch, D.J. et al. (2004) Inactivation of Fatty Acid Transport Protein I Prevents Fat-Induced Insulin Resistance in Skeletal Muscle, J. Clin. Invest. 113, 756–763.

    Article  PubMed  CAS  Google Scholar 

  24. Munday, M.R., and Hemingway, C.J. (1999) The Regulation of Acetyl-Coa Carboxylase—A Potential Target for the Action of Hypolipidemic Agents, Adv. Enzyme Regul. 39, 205–234.

    Article  PubMed  CAS  Google Scholar 

  25. Gaudet, D., Arsenault, S., Perusse, L., Vohl, M.C., St-Pierre, J., Bergeron, J., Despres, J.P., Dewar, K., Daly, M.J., Hudson, T. et al. (2000) Glycerol as a Correlate of Impaired Glucose Tolerance: Dissection of a Complex System by Use of a Simple Genetic Trait, Am. J. Hum. Genet. 66, 1558–1568.

    Article  PubMed  CAS  Google Scholar 

  26. Marshall, B.A., and Mueckler, M.M. (1994) Differential Effects of GLUT-1 or GLUT-4 Overexpression on Insulin Responsiveness in Transgenic Mice, Am. J. Physiol. 267, E738-E744.

    PubMed  CAS  Google Scholar 

  27. Postic, C., Leturque, A., Rencurel, F., Printz, R.L., Forest, C., Granner, D.K., and Girard, J. (1993) The Effects of Hyperinsulinemia and Hyperglycemia on GLUT4 and Hexokinase II mRNA and Protein in Rat Skeletal Muscle and Adipose Tissue. Diabetes 42, 922–929.

    PubMed  CAS  Google Scholar 

  28. Oikonomakos, N. (2002) Glycogen Phosphorylase as a Molecular Target for Type 2 Diabetes Therapy, Curr. Protein Pept. Sci. 3, 561–586.

    Article  PubMed  CAS  Google Scholar 

  29. Wu, P., Blair, P. V., Sato, J., Jaskiewicz, J., Popov, K.M., and Harris, R.A. (2000) Starvation Increases the Amount of Pyruvate Dehydrogenase Kinase in Several Mammalian Tissues. Arch. Biochem. Biophys. 381, 1–7.

    Article  PubMed  CAS  Google Scholar 

  30. Hebert, L.F., Jr., Daniels, M.C., Zhou, J., Crook, E.D., Turner, R.L., Simmons, S.T., Neidigh, J.L., Zhu, J.S., Baron, A.D., and McClain, D.A. (1996) Overexpression of Glutamine: Fructose-6-phosphate Amidotransferase in Transgenic Mice Leads to Insulin Resistance, J. Clin. Invest. 98, 930–936.

    Article  PubMed  CAS  Google Scholar 

  31. Ryu, M.H., and Cha, Y.S. (2003) The Effects of a High-Fat or High-Sucrose Diet on Serum Lipid Profiles, Hepatic Acyl-CoA Synthetase, Carnitinepalmitoyltransferase-I, and the Acetyl-CoA Carboxylase mRNA Levels in Rats, J. Biochem. Mol. Biol. 36, 312–318.

    PubMed  CAS  Google Scholar 

  32. Katz, A., Nambi, S.S., Mather, K., Baron, A.D., Follman, D.A., Sullivan, G., and Quon, M.J. (2000) Quantitative Insulin Sensitivity Check Index: A Simple, Accurate Method for Assessing Insulin Sensitivity in Humans, J. Clin. Endocrinol. Metab. 85, 2402–2410.

    Article  PubMed  CAS  Google Scholar 

  33. Phillips, D.I., Clark, P.M., Hales, C.N., and Osmond, C. (1994) Understanding Oral Glucose Tolerance: Comparison of Glucose or Insulin Measurements During the Oral Glucose Tolerance Test with Specific Measurements of Insulin Resistance and Insulin Secretion, Diabet. Med. 11, 286–292.

    Article  PubMed  CAS  Google Scholar 

  34. Gilboe, D.P., Larson, K.L., and Nuttall, F.Q. (1972) Radioactive Method for the Assay of Glycogen Phosphorylases, Anal. Biochem. 47, 20–27.

    Article  PubMed  CAS  Google Scholar 

  35. Livak, K.J., and Schmittgen, T.D. (2001) Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔC(T) Method, Methods 25, 402–408.

    Article  PubMed  CAS  Google Scholar 

  36. Pfaffl, M.W., Horgan, G.W., and Dempfle, L. (2002) Relative Expression Software Tool (REST) for Group-wise Comparison and Statistical Analysis of Relative Expression Results in Real-Time PCR, Nucleic Acids Res. 30, e36.

    Article  PubMed  Google Scholar 

  37. Armstrong, R.B., and Phelps, R.O. (1984) Muscle Fiber Type Composition of the Rat Hind Limb, Am. J. Anat. 171, 259–272.

    Article  PubMed  CAS  Google Scholar 

  38. Rinella, M.E., and Green, R.M. (2004) The Methionine-Choline Deficient Dietary Model of Steatohepatitis Does Not Exhibit Insulin Resistance, J. Hepatol. 40, 47–51.

    Article  PubMed  CAS  Google Scholar 

  39. Yoneda, H., Ikegami, H., Yamamoto, Y., Yamato, E., Cha, T., Kawaguchi, Y., Tahara, Y., and Ogihara, T. (1992) Analysis of Early-Phase Insulin Responses in Nonobese Subjects with Mild Glucose Intolerance, Diabetes Care 15, 1517–1521.

    PubMed  CAS  Google Scholar 

  40. Grefhorst, A., Elzinga, B.M., Voshol, P.J., Plosch, T., Kok, T., Bloks, V.W., van der Sluijs, F.H., Havekes, L.M., Romijn, J.A., Verkade, H.J. et al. (2002) Stimulation of Lipogenesis by Pharmacological Activation of the Liver X Receptor Leads to Production of Large, Triglyceride-rich Very Low Density Lipoprotein Particles, J. Biol. Chem. 277, 34182–34190.

    Article  PubMed  CAS  Google Scholar 

  41. Ishii, S., Iizuka, K., Miller, B.C., and Uyeda, K. (2004) Carbohydrate Response Element Binding Protein Directly Promotes Lipogenic Enzyme Gene Transcription, Proc. Natl. Acad. Sci. USA 101, 15597–15602.

    Article  PubMed  CAS  Google Scholar 

  42. Stuart, C.A., Wen, G., Williamson, M.E., Jiang, J., Gilkison., C.R., Blackwell, S.J., Nagamani, M., and Ferrando, A.A. (2001) Altered GLUT1 and GLUT3 Gene Expression, and Subcellular Redistribution of GLUT4: Protein in Muscle from Patients with Acanthosis Nigricans and Severe Insulin Resistance, Metabolism 50, 771–777.

    Article  PubMed  CAS  Google Scholar 

  43. Ren, J.-M., Marshall, A., Gulve, E.A., Gao, J., Johnson, D.W., Holloszy, J.O., and Mueckler, M. (1993) Evidence from Transgenic Mice That Glucose Transport Is Rate-Limiting for Glycogen Deposition and Glycolysis in Skeletal Muscle, J. Biol. Chem. 268, 16113–16115.

    PubMed  CAS  Google Scholar 

  44. Osawa, H., Printz, R.L., Whitesell, R.R., and Granner, D.K. (1995) Regulation of Hexokinase II Gene Transcription and Glucose Phosphorylation by Catecholamines, Cyclic AMP, and Insulin, Diabetes 44, 1426–1432.

    PubMed  CAS  Google Scholar 

  45. Arias, E.B., Kim, J., and Cartee, G.D. (2004) Prolonged Incubation in PUGNAc Results in Increased Protein O-Linked Glycosylation and Insulin Resistance in Rat Skeletal Muscle, Diabetes 53, 921–930.

    PubMed  CAS  Google Scholar 

  46. Montell, E., Lerin, C., Newgard, C.B., and Gomez-Foix, A.M. (2002) Effects of Modulation of Glycerol Kinase Expression on Lipid and Carbohydrate Metabolism in Human Muscle Cells, J. Biol. Chem. 277, 2682–2686.

    Article  PubMed  CAS  Google Scholar 

  47. Wu, P., Inskeep, K., Bowker-Kinley, M.M., Popov, K.M., and Harris, R.A. (1999) Mechanism Responsible for Inactivation of Skeletal Muscle Pyruvate Dehydrogenase Complex in Starvation and Diabetes, Diabetes 48, 1593–1599.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Nestlé Research Center, Vers-Chez-Les-Blanc, CH-1000, Lausanne 26, Switzerland

    Marco Turini & Katherine Macé

  2. Department de Bioquímica i Biologia Molecular, Universitat de Barcelona, Av. Diagonal 645, E-08028, Barcelona, Spain

    Andreu Ferrer-Martínez, Mario Marotta & Anna M. Gómèz-Foix

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  1. Andreu Ferrer-Martínez
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  2. Mario Marotta
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  3. Marco Turini
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  5. Anna M. Gómèz-Foix
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Correspondence to Anna M. Gómèz-Foix.

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Ferrer-Martínez, A., Marotta, M., Turini, M. et al. Effect of sucrose and saturated-fat diets on mRNA levels of genes limiting muscle fatty acid and glucose supply in rats. Lipids 41, 55–62 (2006). https://doi.org/10.1007/s11745-006-5070-1

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  • DOI: https://doi.org/10.1007/s11745-006-5070-1

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