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Fructose intake during pregnancy up-regulates the expression of maternal and fetal hepatic sterol regulatory element-binding protein-1c in rats

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Abstract

Excess fructose consumption is associated with the development of type 2 diabetes and obesity. However, the impact of fructose intake on maternal and fetal lipid metabolism during pregnancy is not known. The aim of this study was to examine whether maternal fructose intake during pregnancy would affect fetal and maternal hepatic lipid metabolism. Pregnant Wistar rats were randomly divided into untreated control and fructose-treated groups; the fructose-treated group received fructose via drinking water throughout pregnancy. On gestational day 20, glucose and insulin concentration in the maternal plasma were measured. The mRNA expression of sterol regulatory element-binding protein (SREBP)-1c and its target genes in the liver of dams and fetuses were analyzed by real-time PCR. Significantly higher maternal plasma glucose levels, indicating hyperglycemia, was observed in the fructose-treated group than in the control group. Furthermore, the fructose-treated group showed significantly higher expression levels of both maternal and fetal SREBP-1c mRNA and protein and significantly elevated expression of fatty acid synthase; the group also showed reduced acyl-CoA oxidase levels in the maternal liver. Thus, our results suggest that maternal fructose intake during pregnancy causes maternal hyperglycemia and up-regulates hepatic SREBP-1c expression in both fetuses and dams. This may lead to defects in carbohydrate and lipid metabolism in the adult offspring.

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References

  1. S. Vuilleumier, Worldwide production of high-fructose syrup and crystalline fructose. Am. J. Clin. Nutr. 58, 733S–736S (1993)

    PubMed  CAS  Google Scholar 

  2. S.W. Rizkalla, Health implications of fructose consumption: a review of recent data. Nutr. Metab. 7, 82 (2010)

    Article  Google Scholar 

  3. K.L. Stanhope, P.J. Havel, Fructose consumption: recent results and their potential implications. Ann. N. Y. Acad. Sci. 1190, 15–24 (2010)

    Article  PubMed  CAS  Google Scholar 

  4. S.M. Hofmann, M.H. Tschop, Dietary sugars: a fat difference. J. Clin. Invest. 119, 1089–1092 (2009)

    Article  PubMed  CAS  Google Scholar 

  5. R.J. Johnson, M.S. Segal, Y. Sautin, T. Nakagawa, D.I. Feig, D.H. Kang, M.S. Gersch, S. Benner, L.G. Sanchez-Lozada, Potential role of sugar (fructose) in the epidemic of hypertension, obesity and the metabolic syndrome, diabetes, kidney disease, and cardiovascular disease. Am. J. Clin. Nutr. 86, 899–906 (2007)

    PubMed  CAS  Google Scholar 

  6. A.W. Thorburn, L.H. Storlien, A.B. Jenkins, S. Khouri, E.W. Kraegen, Fructose-induced in vivo insulin resistance and elevated plasma triglyceride levels in rats. Am. J. Clin. Nutr. 49, 1155–1163 (1989)

    PubMed  CAS  Google Scholar 

  7. J. Luo, S.W. Rizkalla, M. Lerer-Metzger, J. Boillot, A. Ardeleanu, F. Bruzzo, A. Chevalier, G. Slama, A fructose-rich diet decreases insulin-stimulated glucose incorporation into lipids but not glucose transport in adipocytes of normal and diabetic rats. J. Nutr. 125, 164–171 (1995)

    PubMed  CAS  Google Scholar 

  8. R.M. Bezerra, M. Ueno, M.S. Silva, D.Q. Tavares, C.R. Carvalho, M.J. Saad, A high fructose diet affects the early steps of insulin action in muscle and liver of rats. J. Nutr. 130, 1531–1535 (2000)

    PubMed  CAS  Google Scholar 

  9. K.L. Stanhope, J.M. Schwarz, N.L. Keim, S.C. Griffen, A.A. Bremer, J.L. Graham, B. Hatcher, C.L. Cox, A. Dyachenko, W. Zhang, J.P. McGahan, A. Seibert, R.M. Krauss, S. Chiu, E.J. Schaefer, M. Ai, S. Otokozawa, K. Nakajima, T. Nakano, C. Beysen, M.K. Hellerstein, L. Berglund, P.J. Havel, Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. J. Clin. Invest. 119, 1322–1334 (2009)

    Article  PubMed  CAS  Google Scholar 

  10. K.L. Teff, S.S. Elliott, M. Tschop, T.J. Kieffer, D. Rader, M. Heiman, R.R. Townsend, N.L. Keim, D. D’Alessio, P.J. Havel, Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. J. Clin. Endocrinol. Metab. 89, 2963–2972 (2004)

    Article  PubMed  CAS  Google Scholar 

  11. N.K. Pollock, V. Bundy, W. Kanto, C.L. Davis, P.J. Bernard, H. Zhu, B. Gutin, Y. Dong, Greater fructose consumption is associated with cardiometabolic risk markers and visceral adiposity in adolescents. J. Nutr. 142, 251–257 (2012)

    Article  PubMed  CAS  Google Scholar 

  12. D.S. Ludwig, K.E. Peterson, S.L. Gortmaker, Relation between consumption of sugar-sweetened drinks and childhood obesity: a prospective, observational analysis. Lancet 357, 505–508 (2001)

    Article  PubMed  CAS  Google Scholar 

  13. S.C. Langley, A.A. Jackson, Increased systolic blood pressure in adult rats induced by fetal exposure to maternal low protein diets. Clin. Sci. 86, 217–222 (1994)

    PubMed  CAS  Google Scholar 

  14. G. Cambonie, B. Comte, C. Yzydorczyk, T. Ntimbane, N. Germain, N.L. Le, P. Pladys, C. Gauthier, I. Lahaie, D. Abran, J.C. Lavoie, A.M. Nuyt, Antenatal antioxidant prevents adult hypertension, vascular dysfunction, and microvascular rarefaction associated with in utero exposure to a low-protein diet. Am. J. Physiol. Regul. Integr. Comp. Physiol. 292, R1236–R1245 (2007)

    Article  PubMed  CAS  Google Scholar 

  15. N. Theys, M.T. Ahn, T. Bouckenooghe, B. Reusens, C. Remacle, Maternal malnutrition programs pancreatic islet mitochondrial dysfunction in the adult offspring. J. Nutr. Biochem. 22, 985–994 (2010)

    Article  PubMed  Google Scholar 

  16. G.J. Howie, D.M. Sloboda, T. Kamal, M.H. Vickers, Maternal nutritional history predicts obesity in adult offspring independent of postnatal diet. J. Physiol. 587, 905–915 (2009)

    Article  PubMed  CAS  Google Scholar 

  17. N.G. Ashino, K.N. Saito, F.D. Souza, F.S. Nakutz, E.A. Roman, L.A. Velloso, A.S. Torsoni, M.A. Torsoni, Maternal high-fat feeding through pregnancy and lactation predisposes mouse offspring to molecular insulin resistance and fatty liver. J. Nutr. Biochem. 23, 341–348 (2011)

    Article  PubMed  Google Scholar 

  18. S. Rawana, K. Clark, S. Zhong, A. Buison, S. Chackunkal, K.L. Jen, Low dose fructose ingestion during gestation and lactation affects carbohydrate metabolism in rat dams and their offspring. J. Nutr. 123, 2158–2165 (1993)

    PubMed  CAS  Google Scholar 

  19. K.L. Jen, C. Rochon, S.B. Zhong, L. Whitcomb, Fructose and sucrose feeding during pregnancy and lactation in rats changes maternal and pup fuel metabolism. J. Nutr. 121, 1999–2005 (1991)

    PubMed  CAS  Google Scholar 

  20. M.A. Fergusson, K.G. Koski, Comparison of effects of dietary glucose versus fructose during pregnancy on fetal growth and development in rats. J. Nutr. 120, 1312–1319 (1990)

    PubMed  CAS  Google Scholar 

  21. M.H. Vickers, Z.E. Clayton, C. Yap, D.M. Sloboda, Maternal fructose intake during pregnancy and lactation alters placental growth and leads to sex-specific changes in fetal and neonatal endocrine function. Endocrinology 152, 1378–1387 (2011)

    Article  PubMed  CAS  Google Scholar 

  22. D.R. Matthews, J.P. Hosker, A.S. Rudenski, B.A. Naylor, D.F. Treacher, R.C. Turner, Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28, 412–419 (1985)

    Article  PubMed  CAS  Google Scholar 

  23. J. Folch, M. Lees, G.H. Sloane Stanley, A simple method for the isolation and purification of total lipides from animal tissues. J. Biol. Chem. 226, 497–509 (1957)

    PubMed  CAS  Google Scholar 

  24. J.M. Keller, P. Collet, A. Bianchi, C. Huin, P. Bouillaud-Kremarik, P. Becuwe, H. Schohn, L. Domenjoud, M. Dauca, Implications of peroxisome proliferator-activated receptors (PPARS) in development, cell life status and disease. Int. J. Dev. Biol. 44, 429–442 (2000)

    PubMed  CAS  Google Scholar 

  25. E.A. Reece, C. Homko, A. Wiznitzer, Metabolic changes in diabetic and nondiabetic subjects during pregnancy. Obstet. Gynecol. Surv. 49, 64–71 (1994)

    Article  PubMed  CAS  Google Scholar 

  26. N.F. Butte, Carbohydrate and lipid metabolism in pregnancy: normal compared with gestational diabetes mellitus. Am. J. Clin. Nutr. 71, 1256S–1261S (2000)

    PubMed  CAS  Google Scholar 

  27. N.V. Costrini, R.K. Kalkhoff, Relative effects of pregnancy, estradiol, and progesterone on plasma insulin and pancreatic islet insulin secretion. J. Clin. Invest. 50, 992–999 (1971)

    Article  PubMed  CAS  Google Scholar 

  28. C. Munoz, P. Lopez-Luna, E. Herrera, Glucose and insulin tolerance tests in the rat on different days of gestation. Biol. Neonate 68, 282–291 (1995)

    Article  PubMed  CAS  Google Scholar 

  29. J. Sleder, Y.D. Chen, M.D. Cully, G.M. Reaven, Hyperinsulinemia in fructose-induced hypertriglyceridemia in the rat. Metabolism 29, 303–305 (1980)

    Article  PubMed  CAS  Google Scholar 

  30. M.J. Dekker, Q. Su, C. Baker, A.C. Rutledge, K. Adeli, Fructose: a highly lipogenic nutrient implicated in insulin resistance, hepatic steatosis, and the metabolic syndrome. Am. J. Physiol. Endocrinol. Metab. 299, E685–E694 (2010)

    Article  PubMed  CAS  Google Scholar 

  31. J.F. Giani, M.A. Mayer, M.C. Munoz, E.A. Silberman, C. Hocht, C.A. Taira, M.M. Gironacci, D. Turyn, F.P. Dominici, Chronic infusion of angiotensin-(1–7) improves insulin resistance and hypertension induced by a high-fructose diet in rats. Am. J. Physiol. Endocrinol. Metab. 296, E262–E271 (2009)

    Article  PubMed  CAS  Google Scholar 

  32. M.S. Strable, J.M. Ntambi, Genetic control of de novo lipogenesis: role in diet-induced obesity. Crit. Rev. Biochem. Mol. Biol. 45, 199–214 (2010)

    Article  PubMed  CAS  Google Scholar 

  33. A.C. Rutledge, K. Adeli, Fructose and the metabolic syndrome: pathophysiology and molecular mechanisms. Nutr. Rev. 65, S13–S23 (2007)

    Article  PubMed  Google Scholar 

  34. Y. Sakar, C. Nazaret, P. Letteron, A. Ait Omar, M. Avenati, B. Viollet, R. Letteron, A. Bado, Positive regulatory control loop between gut leptin and intestinal GLUT2/GLUT5 transporters links to hepatic metabolic functions in rodents. PLoS ONE 4, e7935 (2009)

    Article  PubMed  Google Scholar 

  35. Y. Nagai, Y. Nishio, T. Nakamura, H. Maegawa, R. Kikkawa, A. Kashiwagi, Amelioration of high fructose-induced metabolic derangements by activation of PPARα. Am. J. Physiol. Endocrinol. Metab. 282, E1180–E1190 (2002)

    PubMed  CAS  Google Scholar 

  36. M. Miyazaki, A. Dobrzyn, W.C. Man, K. Chu, H. Sampath, H.J. Kim, J.M. Ntambi, Stearoyl-CoA desaturase 1 gene expression is necessary for fructose-mediated induction of lipogenic gene expression by sterol regulatory element-binding protein-1c-dependent and -independent mechanisms. J. Biol. Chem. 279, 25164–25171 (2004)

    Article  PubMed  CAS  Google Scholar 

  37. T. Takemoto, Y. Nishio, O. Sekine, C. Ikeuchi, Y. Nagai, Y. Maeno, H. Maegawa, H. Kimura, A. Kashiwagi, RBMX is a novel hepatic transcriptional regulator of SREBP-1c gene response to high-fructose diet. FEBS Lett. 581, 218–222 (2007)

    Article  PubMed  CAS  Google Scholar 

  38. S. Shrestha, S.J. Ehlers, J.Y. Lee, M.L. Fernandez, S.I. Koo, Dietary green tea extract lowers plasma and hepatic triglycerides and decreases the expression of sterol regulatory element-binding protein-1c mRNA and its responsive genes in fructose-fed, ovariectomized rats. J. Nutr. 139, 640–645 (2009)

    Article  PubMed  CAS  Google Scholar 

  39. E. Herrera, Lipid metabolism in pregnancy and its consequences in the fetus and newborn. Endocrine 19, 43–55 (2002)

    Article  PubMed  CAS  Google Scholar 

  40. N. Roglans, E. Sanguino, C. Peris, M. Alegret, M. Vazquez, T. Adzet, C. Diaz, G. Hernandez, J.C. Laguna, R.M. Sanchez, Atorvastatin treatment induced peroxisome proliferator-activated receptor alpha expression and decreased plasma nonesterified fatty acids and liver triglyceride in fructose-fed rats. J. Pharmacol. Exp. Ther. 302, 232–239 (2002)

    Article  PubMed  CAS  Google Scholar 

  41. A. Ericsson, K. Saljo, E. Sjostrand, N. Jansson, P.D. Prasad, T.L. Powell, T. Jansson, Brief hyperglycaemia in the early pregnant rat increases fetal weight at term by stimulating placental growth and affecting placental nutrient transport. J. Physiol. 581, 1323–1332 (2007)

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors thank Keiko Tamakuma for her technical assistance. This study was supported by a Grant-in-Aid for Young Scientists B (21700760) from the Japan Society for the Promotion of Science.

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The authors declare that they have no conflict of interest.

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  1. Department of Nutrition, Faculty of Health Sciences, Aomori University of Health and Welfare, Mase 58-1 Hamadate, Aomori, 030-8505, Japan

    Yuuka Mukai, Maya Kumazawa & Shin Sato

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  1. Yuuka Mukai
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  2. Maya Kumazawa
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Correspondence to Yuuka Mukai.

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Mukai, Y., Kumazawa, M. & Sato, S. Fructose intake during pregnancy up-regulates the expression of maternal and fetal hepatic sterol regulatory element-binding protein-1c in rats. Endocrine 44, 79–86 (2013). https://doi.org/10.1007/s12020-012-9815-8

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  • DOI: https://doi.org/10.1007/s12020-012-9815-8

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