Nutrition Research and Practice

The Korean Nutrition Society (한국영양학회)
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Maternal high-fructose intake during pregnancy and lactation induces metabolic syndrome in adult offspring

  • Koo, Soohyeon (Department of Pharmacology, School of Medicine, Kyungpook National University) ;
  • Kim, Mina (Department of Pharmacology, School of Medicine, Kyungpook National University) ;
  • Cho, Hyun Min (Department of Pharmacology, School of Medicine, Kyungpook National University) ;
  • Kim, Inkyeom (Department of Pharmacology, School of Medicine, Kyungpook National University)
  • Received : 2020.03.12
  • Accepted : 2020.08.30
  • Published : 2021.04.01
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Abstract

BACKGROUND/OBJECTIVES: Nutritional status and food intake during pregnancy and lactation can affect fetal programming. In the current metabolic syndrome epidemic, high-fructose diets have been strongly implicated. This study investigated the effect of maternal high-fructose intake during pregnancy and lactation on the development of metabolic syndrome in adult offspring. SUBJECTS/METHODS: Drinking water with or without 20% fructose was administered to female C57BL/6J mice over the course of their pregnancy and lactation periods. After weaning, pups ate regular chow. Accu-Chek Performa was used to measure glucose levels, and a tail-cuff method was used to examine systolic blood pressure. Animals were sacrificed at 7 months, their livers were excised, and sections were stained with Oil Red O and hematoxylin and eosin (H&E) staining. Kidneys were collected for gene expression analysis using quantitative real-time Polymerase chain reaction. RESULTS: Adult offspring exposed to maternal high-fructose intake during pregnancy and lactation presented with heavier body weights, fattier livers, and broader areas under the curve in glucose tolerance test values than control offspring. Serum levels of alanine aminotransferase, aspartate aminotransferase, glucose, triglycerides, and total cholesterol and systolic blood pressure in the maternal high-fructose group were higher than that in controls. However, there were no significant differences in mRNA expressions of renin-angiotensin-aldosterone system genes and sodium transporter genes. CONCLUSIONS: These results suggest that maternal high-fructose intake during pregnancy and lactation induces metabolic syndrome with hyperglycemia, hypertension, and dyslipidemia in adult offspring.

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References

  1. Vieau D. Perinatal nutritional programming of health and metabolic adult disease. World J Diabetes 2011;2:133-6. https://doi.org/10.4239/wjd.v2.i9.133
  2. Kruse M, Seki Y, Vuguin PM, Du XQ, Fiallo A, Glenn AS, Singer S, Breuhahn K, Katz EB, Charron MJ. High-fat intake during pregnancy and lactation exacerbates high-fat diet-induced complications in male offspring in mice. Endocrinology 2013;154:3565-76. https://doi.org/10.1210/en.2012-1877
  3. Yamazaki M, Yamada H, Munetsuna E, Ishikawa H, Mizuno G, Mukuda T, Mouri A, Nabeshima T, Saito K, Suzuki K, Hashimoto S, Ohashi K. Excess maternal fructose consumption impairs hippocampal function in offspring via epigenetic modification of BDNF promoter. FASEB J 2018;32:2549-62. https://doi.org/10.1096/fj.201700783rr
  4. Bleich SN, Vercammen KA, Koma JW, Li Z. Trends in beverage consumption among children and adults, 2003-2014. Obesity (Silver Spring) 2018;26:432-41. https://doi.org/10.1002/oby.22056
  5. Sundborn G, Thornley S, Merriman TR, Lang B, King C, Lanaspa MA, Johnson RJ. Are liquid sugars different from solid sugar in their ability to cause metabolic syndrome? Obesity (Silver Spring) 2019;27:879-87. https://doi.org/10.1002/oby.22472
  6. Lindqvist A, Baelemans A, Erlanson-Albertsson C. Effects of sucrose, glucose and fructose on peripheral and central appetite signals. Regul Pept 2008;150:26-32. https://doi.org/10.1016/j.regpep.2008.06.008
  7. Hannou SA, Haslam DE, McKeown NM, Herman MA. Fructose metabolism and metabolic disease. J Clin Invest 2018;128:545-55. https://doi.org/10.1172/jci96702
  8. Gaston SA, Tulve NS, Ferguson TF. Abdominal obesity, metabolic dysfunction, and metabolic syndrome in U.S. adolescents: National Health and Nutrition Examination Survey 2011-2016. Ann Epidemiol 2019;30:30-6. https://doi.org/10.1016/j.annepidem.2018.11.009
  9. Li Y, Zhao L, Yu D, Wang Z, Ding G. Metabolic syndrome prevalence and its risk factors among adults in China: a nationally representative cross-sectional study. PLoS One 2018;13:e0199293. https://doi.org/10.1371/journal.pone.0199293
  10. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Costa FAmerican Heart AssociationNational Heart, Lung, and Blood Institute. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005;112:2735-52. https://doi.org/10.1161/CIRCULATIONAHA.105.169404
  11. Mule G, Calcaterra I, Nardi E, Cerasola G, Cottone S. Metabolic syndrome in hypertensive patients: an unholy alliance. World J Cardiol 2014;6:890-907. https://doi.org/10.4330/wjc.v6.i9.890
  12. Wynne BM, Mistry AC, Al-Khalili O, Mallick R, Theilig F, Eaton DC, Hoover RS. Aldosterone modulates the association between NCC and ENaC. Sci Rep 2017;7:4149. https://doi.org/10.1038/s41598-017-03510-5
  13. McDonough AA, Nguyen MT. Maintaining balance under pressure: integrated regulation of renal transporters during hypertension. Hypertension 2015;66:450-5. https://doi.org/10.1161/HYPERTENSIONAHA.115.04593
  14. Gligorovska L, Bursac B, Kovacevic S, Velickovic N, Matic G, Djordjevic A. Mif deficiency promotes adiposity in fructose-fed mice. J Endocrinol 2019;240:133-45. https://doi.org/10.1530/JOE-18-0333
  15. Wang Y, Thatcher SE, Cassis LA. Measuring blood pressure using a noninvasive tail cuff method in mice. Methods Mol Biol 2017;1614:69-73. https://doi.org/10.1007/978-1-4939-7030-8_6
  16. Seong HY, Cho HM, Kim M, Kim I. Maternal high-fructose intake induces multigenerational activation of the renin-angiotensin-aldosterone system. Hypertension 2019;74:518-25. https://doi.org/10.1161/hypertensionaha.119.12941
  17. Wu G, Bazer FW, Cudd TA, Meininger CJ, Spencer TE. Maternal nutrition and fetal development. J Nutr 2004;134:2169-72. https://doi.org/10.1093/jn/134.9.2169
  18. Chapman DJ, Nommsen-Rivers L. Impact of maternal nutritional status on human milk quality and infant outcomes: an update on key nutrients. Adv Nutr 2012;3:351-2. https://doi.org/10.3945/an.111.001123
  19. Vickers MH, Clayton ZE, Yap C, Sloboda DM. Maternal fructose intake during pregnancy and lactation alters placental growth and leads to sex-specific changes in fetal and neonatal endocrine function. Endocrinology 2011;152:1378-87. https://doi.org/10.1210/en.2010-1093
  20. Clayton ZE, Vickers MH, Bernal A, Yap C, Sloboda DM. Early life exposure to fructose alters maternal, fetal and neonatal hepatic gene expression and leads to sex-dependent changes in lipid metabolism in rat offspring. PLoS One 2015;10:e0141962. https://doi.org/10.1371/journal.pone.0141962
  21. Pereira RM, Botezelli JD, da Cruz Rodrigues KC, Mekary RA, Cintra DE, Pauli JR, da Silva AS, Ropelle ER, de Moura LP. Fructose consumption in the development of obesity and the effects of different protocols of physical exercise on the hepatic metabolism. Nutrients 2017;9:405. https://doi.org/10.3390/nu9040405
  22. Softic S, Gupta MK, Wang GX, Fujisaka S, O'Neill BT, Rao TN, Willoughby J, Harbison C, Fitzgerald K, Ilkayeva O, Newgard CB, Cohen DE, Kahn CR. Divergent effects of glucose and fructose on hepatic lipogenesis and insulin signaling. J Clin Invest 2017;127:4059-74. https://doi.org/10.1172/JCI94585
  23. Horton JD, Shimomura I. Sterol regulatory element-binding proteins: activators of cholesterol and fatty acid biosynthesis. Curr Opin Lipidol 1999;10:143-50. https://doi.org/10.1097/00041433-199904000-00008
  24. Kim M, Lee HA, Cho HM, Kang SH, Lee E, Kim IK. Histone deacetylase inhibition attenuates hepatic steatosis in rats with experimental Cushing's syndrome. Korean J Physiol Pharmacol 2018;22:23-33. https://doi.org/10.4196/kjpp.2018.22.1.23
  25. Wakil SJ, Abu-Elheiga LA. Fatty acid metabolism: target for metabolic syndrome. J Lipid Res 2009;50 Suppl:S138-43. https://doi.org/10.1194/jlr.R800079-JLR200
  26. Mashima T, Seimiya H, Tsuruo T. De novo fatty-acid synthesis and related pathways as molecular targets for cancer therapy. Br J Cancer 2009;100:1369-72. https://doi.org/10.1038/sj.bjc.6605007
  27. Nagai Y, Yonemitsu S, Erion DM, Iwasaki T, Stark R, Weismann D, Dong J, Zhang D, Jurczak MJ, Loffler MG, Cresswell J, Yu XX, Murray SF, Bhanot S, Monia BP, Bogan JS, Samuel V, Shulman GI. The role of peroxisome proliferator-activated receptor gamma coactivator-1 beta in the pathogenesis of fructoseinduced insulin resistance. Cell Metab 2009;9:252-64. https://doi.org/10.1016/j.cmet.2009.01.011
  28. Tomlinson JW, Finney J, Gay C, Hughes BA, Hughes SV, Stewart PM. Impaired glucose tolerance and insulin resistance are associated with increased adipose 11beta-hydroxysteroid dehydrogenase type 1 expression and elevated hepatic 5alpha-reductase activity. Diabetes 2008;57:2652-60. https://doi.org/10.2337/db08-0495
  29. DiStefano JK. Fructose-mediated effects on gene expression and epigenetic mechanisms associated with NAFLD pathogenesis. Cell Mol Life Sci 2020;77:2079-90. https://doi.org/10.1007/s00018-019-03390-0
  30. Cho HM, Kim I. Maternal high-fructose intake induces hypertension through activating histone codes on the (pro)renin receptor promoter. Biochem Biophys Res Commun 2020;527:596-602. https://doi.org/10.1016/j.bbrc.2020.04.081
  31. Horita S, Nakamura M, Suzuki M, Satoh N, Suzuki A, Homma Y, Nangaku M. The role of renal proximal tubule transport in the regulation of blood pressure. Kidney Res Clin Pract 2017;36:12-21. https://doi.org/10.23876/j.krcp.2017.36.1.12
  32. Zhuo JL, Li XC. Proximal nephron. Compr Physiol 2013;3:1079-123. https://doi.org/10.1002/cphy.c110061
  33. Cogan MG. Angiotensin II: a powerful controller of sodium transport in the early proximal tubule. Hypertension 1990;15:451-8. https://doi.org/10.1161/01.HYP.15.5.451
  34. Prasad GV. Metabolic syndrome and chronic kidney disease: current status and future directions. World J Nephrol 2014;3:210-9. https://doi.org/10.5527/wjn.v3.i4.210
  35. Schieber M, Chandel NS. ROS function in redox signaling and oxidative stress. Curr Biol 2014;24:R453-62. https://doi.org/10.1016/j.cub.2014.03.034
  36. Bedard K, Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 2007;87:245-313. https://doi.org/10.1152/physrev.00044.2005
  37. Stasia MJ. CYBA encoding p22(phox), the cytochrome b558 alpha polypeptide: gene structure, expression, role and physiopathology. Gene 2016;586:27-35. https://doi.org/10.1016/j.gene.2016.03.050
  38. Fukai T, Ushio-Fukai M. Superoxide dismutases: role in redox signaling, vascular function, and diseases. Antioxid Redox Signal 2011;15:1583-606. https://doi.org/10.1089/ars.2011.3999
  39. Hotamisligil GS. Inflammation and metabolic disorders. Nature 2006;444:860-7. https://doi.org/10.1038/nature05485
  40. Catrysse L, van Loo G. Inflammation and the metabolic syndrome: the tissue-specific functions of NF-κB. Trends Cell Biol 2017;27:417-29. https://doi.org/10.1016/j.tcb.2017.01.006
  41. DiNicolantonio JJ, Mehta V, Onkaramurthy N, O'Keefe JH. Fructose-induced inflammation and increased cortisol: a new mechanism for how sugar induces visceral adiposity. Prog Cardiovasc Dis 2018;61:3-9. https://doi.org/10.1016/j.pcad.2017.12.001
  42. Kawasaki N, Asada R, Saito A, Kanemoto S, Imaizumi K. Obesity-induced endoplasmic reticulum stress causes chronic inflammation in adipose tissue. Sci Rep 2012;2:799. https://doi.org/10.1038/srep00799
  43. Song D, Arikawa E, Galipeau D, Battell M, McNeill JH. Androgens are necessary for the development of fructose-induced hypertension. Hypertension 2004;43:667-72. https://doi.org/10.1161/01.hyp.0000118018.77344.4e
  44. Vasudevan H, Xiang H, McNeill JH. Differential regulation of insulin resistance and hypertension by sex hormones in fructose-fed male rats. Am J Physiol Heart Circ Physiol 2005;289:H1335-42. https://doi.org/10.1152/ajpheart.00399.2005
  45. Vasudevan H, Yuen VG, McNeill JH. Testosterone-dependent increase in blood pressure is mediated by elevated Cyp4A expression in fructose-fed rats. Mol Cell Biochem 2012;359:409-18. https://doi.org/10.1007/s11010-011-1035-7
  46. Sharma N, Li L, Ecelbarger CM. Sex differences in renal and metabolic responses to a high-fructose diet in mice. Am J Physiol Renal Physiol 2015;308:F400-10. https://doi.org/10.1152/ajprenal.00403.2014

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