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Metabolic programming in offspring of mice fed fructose during pregnancy and lactation

Published online by Cambridge University Press:  10 September 2021

Marina Lummertz Magenis ,
Adriani Paganini Damiani ,
Gustavo de Bem Silveira ,
Ligia Salvan Dagostin ,
Pamela Souza de Marcos ,
Emanuel de Souza ,
Laura de Roch Casagrande ,
Luiza Martins Longaretti ,
Paulo Cesar Lock Silveira  and
Vanessa Moraes de Andrade Open the ORCID record for Vanessa Moraes de Andrade [Opens in a new window]
Marina Lummertz Magenis
Affiliation:
Laboratory of Translational Biomedicine, Graduate Program of Health Sciences, University of Southern Santa Catarina – UNESC, Criciúma, SC, Brazil
Adriani Paganini Damiani
Affiliation:
Laboratory of Translational Biomedicine, Graduate Program of Health Sciences, University of Southern Santa Catarina – UNESC, Criciúma, SC, Brazil
Gustavo de Bem Silveira
Affiliation:
Laboratory of Experimental Pathophysiology, Graduate Program of Health Sciences, University of Southern Santa Catarina – UNESC, Criciúma, SC, Brazil
Ligia Salvan Dagostin
Affiliation:
Laboratory of Translational Biomedicine, Graduate Program of Health Sciences, University of Southern Santa Catarina – UNESC, Criciúma, SC, Brazil
Pamela Souza de Marcos
Affiliation:
Laboratory of Translational Biomedicine, Graduate Program of Health Sciences, University of Southern Santa Catarina – UNESC, Criciúma, SC, Brazil
Emanuel de Souza
Affiliation:
Course of Biomedicine, University of Southern Santa Catarina – UNESC, Criciúma, SC, Brazil
Laura de Roch Casagrande
Affiliation:
Laboratory of Experimental Pathophysiology, Graduate Program of Health Sciences, University of Southern Santa Catarina – UNESC, Criciúma, SC, Brazil
Luiza Martins Longaretti
Affiliation:
Laboratory of Translational Biomedicine, Graduate Program of Health Sciences, University of Southern Santa Catarina – UNESC, Criciúma, SC, Brazil
Paulo Cesar Lock Silveira
Affiliation:
Laboratory of Experimental Pathophysiology, Graduate Program of Health Sciences, University of Southern Santa Catarina – UNESC, Criciúma, SC, Brazil
Vanessa Moraes de Andrade*
Affiliation:
Laboratory of Translational Biomedicine, Graduate Program of Health Sciences, University of Southern Santa Catarina – UNESC, Criciúma, SC, Brazil
*
Address for correspondence: Vanessa Moraes de Andrade, Laboratory of Translational Biomedicine, Graduate Program of Health Sciences, Department of Health Sciences, University of Southern Santa Catarina, UNESC, 1105, Universitária Rd, 88806000, Criciúma, SC, Brazil. Email: vmoraesdeandrade@yahoo.com.br
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Abstract

Fructose (C6H12O6), also known as levulose, is a hexose. Chronic consumption of fructose may be associated with increased intrahepatic fat concentration and the development of insulin resistance as well as an increase in the prevalence of nonalcoholic fatty liver disease and hyperlipidemia during pregnancy. Despite the existence of many studies regarding the consumption of fructose in pregnancy, its effects on fetuses have not yet been fully elucidated. Therefore, the objective of this study was to evaluate the genetic and biochemical effects in offspring (male and female) of female mice treated with fructose during pregnancy and lactation. Pairs of 60-day-old Swiss mice were used and divided into three groups; negative control and fructose, 10%/l and 20%/l doses of fructose groups. After offspring birth, the animals were divided into six groups: P1 and P2 (males and females), water; P3 and P4 (males and females) fructose 10%/l; and P5 and P6 (males and females) fructose 20%/l. At 30 days of age, the animals were euthanized for genetic and biochemical assessments. Female and male offspring from both dosage groups demonstrated genotoxicity (evaluated through comet assay) and oxidative stress (evaluated through nitrite concentration, sulfhydril content and superoxide dismutase activity) in peripheral and brain tissues. In addition, they showed nutritional and metabolic changes due to the increase in food consumption, hyperglycemia, hyperlipidemia, and metabolic syndrome. Therefore, it is suggested that high consumption of fructose by pregnant female is harmful to their offspring. Thus, it is important to carry out further studies and make pregnant women aware of excessive fructose consumption during this period.

Keywords

Fructosepregnancyoffspringgenotoxicitybiochemistry
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 13 , Issue 4 , August 2022 , pp. 441 - 454
Copyright
© The Author(s), 2021. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease

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References

Gaino, NM, Silva, MV. Consumo de frutose e impacto na saúde humana. SAN. 2011; 18, 88–98. DOI 10.20396/san.v18i2.8634681.Google Scholar
Tappy, L. Fructose metabolism and noncommunicable diseases: recent findings and new research perspectives. Curr Opin Clin Nutr Metab Care. 2018; 5(3), 214–222. DOI 10.1097/MCO.0000000000000460.CrossRefGoogle Scholar
Oishi, K, Konishi, T, Hashimoto, C, Yamamoto, S, Takahashi, Y, Shiina, Y. Dietary fish oil differentially ameliorates high-fructose diet-induced hepatic steatosis and hyperlipidemia in mice depending on time of feeding. Nutr Biochem. 2018; 52, 45–53. DOI 10.1016/j.jnutbio.2017.09.024.CrossRefGoogle ScholarPubMed
Tappy, L, Lê, KA. Metabolic effects of fructose and the worldwide increase in obesity. Physiol Rev. 2010; 90(1), 23–46. DOI 10.1152/physrev.00019.2009.CrossRefGoogle ScholarPubMed
Zhang, DM, Jiao, RQ, Kong, LD. High dietary fructose: direct or indirect dangerous factors disturbing tissue and organ functions. Nutrients. 2017; 9(4), 2017–2335. DOI 10.3390/nu9040335.CrossRefGoogle ScholarPubMed
Azqueta, A, Shaposhnikov, S, Collins, AR. DNA oxidation: investigating its key role in environmental mutagenesis with the comet assay. Mutat Res. 2009; 674(1-2), 101–108. DOI 10.1016/j.mrgentox.2008.10.013.CrossRefGoogle ScholarPubMed
Ajiboye, TO, Hussaini, AA, Nafiu, BY, Ibitoye, OB. Aqueous seed extract of Hunteria umbellata (K. Schum.) Hallier f. (Apocynaceae) palliates hyperglycemia, insulin resistance, dyslipidemia, inflammation and oxidative stress in high-fructose diet-induced metabolic syndrome in rats. J Ethnopharmacol. 2017; 23(28), 184–193. DOI 0.1016/j.jep.2016.11.043.CrossRefGoogle Scholar
Nishikawa, T, Sasahara, T, Kiritoshi, S, et al. Evaluation of urinary 8-hydroxydeoxy-guanosine as a novel biomarker of macrovascular complications in type 2 diabetes. Diabetes Care. 2003; 26(5), 1507–1512. DOI 10.2337/diacare.26.5.1507.CrossRefGoogle ScholarPubMed
Weeden, CE, Asselin-Labat, ML. Mechanisms of DNA damage repair in adult stem cells and implications for cancer formation. Mol Basis Dis. 2017; 1864(1), 89–101. DOI 10.1016/j.bbadis.2017.10.015.CrossRefGoogle ScholarPubMed
Gutteridge, JM, Halliwel, B. Antioxidants: molecules, medicines, and myths. Biochem Biophys Res Commun. 2010; 393(4), 561–564. DOI 10.1016/j.bbrc.2010.02.071.CrossRefGoogle ScholarPubMed
Moreli, JB, Santos, JH, Rocha, CR, et al. DNA damage and its cellular response in mother and fetus exposed to hyperglycemic environment. BioMed Res. Int. 2014; 676758(11), 1–9. DOI 10.1155/2014/676758.CrossRefGoogle Scholar
Furness, DLF, Dekkerb, GA, Roberts, CT. DNA damage and health in pregnancy. J Reprod. mmunol. 2011; 89(2), 153–162. DOI 10.1016/j.jri.2011.02.004.CrossRefGoogle ScholarPubMed
White, CE, Piper, EL, Noland, PR, Daniels, LB. Fructose utilization for nucleic acid synthesis in the fetal pig. J Anim Sci. 1982; 55(1), 73–76. DOI 10.2527/jas1982.55173x.CrossRefGoogle ScholarPubMed
Magenis, ML, Damiani, AP, Marcos, PS, et al. Fructose consumption during pregnancy and lactation causes DNA damage and biochemical changes in female mice. Mutagenesis. 2020; 35(2), 179–187. DOI 10.1093/mutage/geaa001.CrossRefGoogle ScholarPubMed
Mizuno, G, Munetsuna, E, Yamada, H, et al. Fructose intake during gestation and lactation differentially affects the expression of hippocampal neurosteroidogenic enzymes in rat offspring. Endocr Res. 2017; 42(1), 71–77. DOI 10.1080/07435800.2016.1182186.CrossRefGoogle ScholarPubMed
Diniz, YS, Faine, LA, Galhardi, CM, et al. Monosodium glutamate in standard and high-fiber diets: metabolic syndrome and oxidative stress in rats. Nutrition. 2005; 21(6), 749–755. DOI 10.1016/j.nut.2004.10.013.CrossRefGoogle ScholarPubMed
Diniz, YS, Fernandes, AA, Campos, KE, et al. Toxicity of hypercaloric diet and monosodium glutamate: oxidative stress and metabolic shifting in hepatic tissue. Food Chem Toxicol. 2004; 42(2), 313–319. DOI 10.1016/j.fct.2003.09.006.CrossRefGoogle ScholarPubMed
Wajchenberg, BL, Santomauro, ATMG, Nery, M, et al. Resistência à insulina: Métodos diagnósticos e fatores que influenciam a Ação da insulina. Arq Bras Endocrinol Metab. 1999; 43, 76–85. DOI 10.1590/S0004-27301999000200003.CrossRefGoogle Scholar
Sociedade Brasileira de Cardiologia. I diretriz brasileira de diagnóstico e tratamento da Síndrome metabólica. Arq Bras Cardiol. 2005; 84(1). DOI 10.1590/S0066-782X2005000700001.Google Scholar
Singh, NP, McCoy, MT, Tice, RR, Schneider, EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res. 1988; 175(1), 184–191. DOI 10.1016/0014-4827(88)90265-0.CrossRefGoogle ScholarPubMed
Tice, RR, Agurell, E, Anderson, D, et al. Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen. 2000; 35, 206–221. DOI 10.1002/(sici)1098-2280(2000)35:.3.0.CO;2-J>CrossRefGoogle ScholarPubMed
Collins, AR, Yamani, NE, Lorenzo, Y, Shaposhnikov, S, Brunborg, G, Azqueta, A. Controlling variation in the comet assay. Front Genet. 2014; 5, 359. DOI 10.3389/fgene.2014.00359.CrossRefGoogle ScholarPubMed
Azqueta, A, Collins, AR. The essential comet assay: a comprehensive guide to measuring DNA damage and repair. Arch Toxicol. 2013; 87, 949–968. DOI 10.1007/s00204-013-1070-0.CrossRefGoogle ScholarPubMed
Mavournin, KH, Blakey, DH, Cimino, MC, Salamone, MF, Heddle, JA. The in vivo micronucleus assay in mammalian bone marrow and peripheral blood, a report of the US Environmental Protection Agency Gene-Tox Program. Mutat Res. 1990; 239, 29–80. DOI 10.1016/0165-1110(90)90030-f.CrossRefGoogle Scholar
Krishna, G, Hayashi, M. In vivo rodent micronucleus assay: protocol, conduct and data interpretation. Mutat Res. 2000; 455, 155–166. DOI 10.1016/s0027-5107(00)00117-2.CrossRefGoogle ScholarPubMed
Chae, SY, Lee, M, Kim, SW, Bae, YHJB. Protection of insulin secreting cells from nitric oxide induced cellular damage by crosslinked hemoglobin. Acs Sym Ser. 2004; 25(5), 843–850. DOI 10.1016/s0142-9612(03)00605-7.Google ScholarPubMed
Aksenov, MY, Markesbery, WR. Changes in thiol content and expression of glutathione redox system genes in the hippocampus and cerebellum in alzheimer’s disease. Neurosci Lett. 2001; 302(2-3), 141–145. DOI 10.1016/s0304-3940(01)01636-6.CrossRefGoogle ScholarPubMed
Bannister, JV, Calabrese, L. Assays for superoxide dismutase. Methods Biochem Anal. 1987; 32, 279–312. DOI 10.1002/9780470110539.ch5.Google ScholarPubMed
Lowry, OH, Rosebrough, NJ, Farr, AL, Randall, RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951; 193(1), 265–275.CrossRefGoogle ScholarPubMed
Gluckman, PD, Hanson, MA. The developmental origins of the metabolic syndrome. Trends Endocrinol Metab. 2004; 15(4), 183–187. DOI 10.1016/j.tem.2004.03.002.CrossRefGoogle ScholarPubMed
Frias, AE, Grove, KL. Obesity: a transgenerational problem linked to nutrition during pregnancy. Semin Reprod Med. 2012; 30, 472–478. DOI 10.1055/s-0032-1328875.Google ScholarPubMed
Ravelli, GP, Stein, ZA, Susser, MW. Obesity in young men after famine exposure in utero and early infancy. N Engl J Med. 1976; 295(7), 349–353. DOI 10.1056/NEJM197608122950701.CrossRefGoogle ScholarPubMed
Trout, KK, Wetzel-Effinger, L. Flavor learning in utero and its implications for future obesity and diabetes. Curr Diab Rep. 2012; 12(1), 60–66. DOI 10.1007/s11892-011-0237-4.CrossRefGoogle ScholarPubMed
Lee, WC, Wu, KLH, Leu, S, Tain, YL. Translational insights on developmental origins of metabolic syndrome: focus on fructose consumption. Biomed J. 2018; 41(2), 96–101. DOI 10.1016/j.bj.2018.02.006.CrossRefGoogle ScholarPubMed
Rodríguez, L, Panadero, MI, Rodrigo, S, et al. Liquid fructose in pregnancy exacerbates fructose-induced dyslipidemia in adult female offspring. J. Nutr Biochem. 2016; 32, 115–122. DOI 10.1016/j.jnutbio.2016.02.013.CrossRefGoogle ScholarPubMed
Abe, T, Yamamoto, S, Konishi, T, Takahashi, Y, Oishi, K. Maternal fish oil supplementation ameliorates maternal high-fructose diet-induced dyslipidemia in neonatal mice with suppression of lipogenic gene expression in livers of postpartum mice. Nutr Res. 2020; 82(Suppl. 1), 34–43. DOI 10.1016/j.nutres.2020.07.003.CrossRefGoogle ScholarPubMed
Ornellas, F, Carapeto, PV, Aguila, MB, Mandarim-de-Lacerda, CA. Sex-linked changes and high cardiovascular risk markers in the mature progeny of father, mother, or both father and mother consuming a high-fructose diet. Nutrition. 2020; 71, 110612. DOI 10.1016/j.nut.2019.110612.CrossRefGoogle ScholarPubMed
Crescenzo, R, Cigliano, L, Mazzoli, A, et al. Early effects of a low fat, fructose-rich diet on liver metabolism, insulin signaling, and oxidative stress in young and adult rats. Front Physiol. 2018; 26, 411. DOI 10.3389/fphys.2018.00411.CrossRefGoogle Scholar
Toop, CR, Gentili, S. Fructose beverage consumption induces a metabolic syndrome phenotype in the rat: a systematic review and meta-analysis. Nutrients. 2016; 8(9). DOI 10.3390/nu8090577.CrossRefGoogle ScholarPubMed
Ross, PJ, Canovas, S. Mechanisms of epigenetic remodelling during preimplantation development. Reprod Fert Develop. 2016; 28(2), 25–40. DOI 10.1071/RD15365.CrossRefGoogle ScholarPubMed
Carapeto, PV, Ornellas, F, Mandarim-de-Lacerda, CA, Aguila, MB. Liver metabolism in adult male mice offspring: consequences of a maternal, paternal or both maternal and paternal high-fructose diet. J Dev Orig Health Dis. 2018; 9(4), 450–459. DOI 10.1017/S2040174418000235.CrossRefGoogle ScholarPubMed
Jang, C, Hui, S, Lu, W, et al. The small intestine converts dietary fructose into glucose and organic acids. Cell Metab. 2018; 27(2), 351–361. DOI 10.1016/j.cmet.2017.12.016.CrossRefGoogle ScholarPubMed
Zhao, XJ, Yu, HW, Yang, YZ, et al. Polydatin prevents fructose-induced liver inflammation and lipid deposition through increasing miR-200a to regulate Keap1/Nrf2 pathway. Redox Biol. 2018; 18, 124–137. DOI 10.1016/j.redox.2018.07.002.CrossRefGoogle ScholarPubMed
King, JC. Physiology of pregnancy and nutrient metabolism. Am J Clin Nutr. 2000; 71(5), 1218S–25S. DOI 10.1093/ajcn/71.5.1218s.CrossRefGoogle ScholarPubMed
Yamada-Obara, N, Yamagishi, SI, Taguchi, K, et al. Maternal exposure to high-fat and high-fructose diet evokes hypoadiponectinemia and kidney injury in rat offspring. Clin Exp Nephrol. 2016; 20(6), 853–861. DOI 10.1007/s10157-016-1265-9.CrossRefGoogle ScholarPubMed
Zaki, SM, Fattah, SA, Hassan, DS. The differential effects of high-fat and high fructose diets on the liver of male albino rat and the proposed underlying mechanisms. Folia Morphol (Warsz). 2019; 78, 124–136. DOI 10.5603/FM.a2018.0063.Google ScholarPubMed
Dos Santos, JM, Oliveira, DS, Moreli, ML, Benite-Ribeiro, SA. The role of mitochondrial DNA damage at skeletal muscle oxidative stress on the development of type 2 diabetes. Mol Cell Biochem. 2018; 449(1-2), 251–255. DOI 10.1007/s11010-018-3361-5.CrossRefGoogle ScholarPubMed
Talton, OO, Bates, K, Salazar, SR, Ji, T, Schulz, LC. Lean maternal hyperglycemia alters offspring lipid metabolism and susceptibility to diet-induced obesity in mice. Biol Reprod. 2019; 100(5), 1356–1369. DOI 10.1093/biolre/ioz009.CrossRefGoogle Scholar
Vitaglione, P, Morisco, F, Caporaso, N, Fogliano, V. Dietary antioxidant compounds and liver health. Crit Rev Food Sci Nutr. 2005; 44, 575–586. DOI 10.1080/10408690490911701.CrossRefGoogle Scholar
Gutiérrez-Camacho, LR, Kormanovski, A, Castillo-Hernández, MD, Guevara-Balcázar, G, Lara-Padilla, E. Alterations in glutathione, nitric oxide and 3‐nitrotyrosine levels following exercise and/or hyperbaric oxygen treatment in mice with diet‐induced diabetes. Biomed Rep. 2020; 12, 222–232. DOI 10.3892/br.2020.1291.Google ScholarPubMed
Mastrocola, R, Nigro, D, Cento, AS, Chiazza, F, Collino, M, Aragno, M. High-fructose intake as risk factor for neurodegeneration: key role for carboxy methyllysine accumulation in mice hippocampal neurons. Neurobiol Dis. 2016; 89(6), 65–75. DOI 10.1016/j.nbd.2016.02.005.CrossRefGoogle ScholarPubMed
Franke, SIR, Molz, P, Mai, C, Wanger, JHE, Zenkner, FF, Horta, JA, Prá, D. High consumption of sucrose induces DNA damage in male Wistar rats. An Acad Bras Ciênc. 2017; 89(4), 2657–2662. DOI 10.1590/0001-3765201720160659.CrossRefGoogle ScholarPubMed
Yamazaki, M, Yamada, H, Munetsuna, E, et al. Excess maternal fructose consumption impairs hippocampal function in offspring via epigenetic modification of BDNF promoter. FASEB J. 2018; 32(5), 2549–2562. DOI 10.1096/fj.201700783RR.CrossRefGoogle ScholarPubMed
Pérez-Corredor, PA, Gutiérrez-Vargas, JA, Ciro-Ramírez, L, Balcazar, N, Cardona-Gómez, GP. High fructose diet-induced obesity worsens post-ischemic brain injury in the hippocampus of female rats. Nutr Neurosci. 2020, 1–15. DOI 10.1080/1028415X.2020.1724453.Google ScholarPubMed