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Intrauterine exposure to a high-fat diet, with different levels of lipids, and its gastrointestinal repercussions: a model of fetal programming in rats

Published online by Cambridge University Press:  23 December 2024

Jéssica Fortunato-Silva ,
Lívia Prometti de Rezende ,
Marcos Luiz Ferreira-Neto ,
Luiz Borges Bispo-da-Silva  and
Ana Paula Coelho Balbi Open the ORCID record for Ana Paula Coelho Balbi [Opens in a new window]
Jéssica Fortunato-Silva
Affiliation:
Program in Applied Structural and Cellular Biology, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Brazil
Lívia Prometti de Rezende
Affiliation:
Program in Applied Structural and Cellular Biology, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Brazil
Marcos Luiz Ferreira-Neto
Affiliation:
Department of Physiology, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Brazil
Luiz Borges Bispo-da-Silva
Affiliation:
Department of Pharmacology, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Brazil
Ana Paula Coelho Balbi*
Affiliation:
Department of Physiology, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Brazil
*
Corresponding author: Ana Paula Coelho Balbi; Email: paulabalb@yahoo.com.br
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Abstract

It is known that adverse stimuli, such as altered diets during pregnancy and lactation, can result in deleterious effects on the progeny. The aim of this study was to evaluate the possible gastrointestinal repercussions in the offspring of Wistar rats exposed to high-fat diets. Pregnant rats were divided into three groups: normolipidic diet (3.5% lipids), a diet containing 28% lipids, and a diet with 40% lipids. Body weight and food, water, daily caloric, and macronutrient intake were evaluated in the pregnant rats. Structural and functional gastrointestinal parameters were assessed in 30-day-old male pups. Depending on the lipid content of the maternal diet, the pups may exhibit gastric mucosal thickening, an increase in the relative weight of the small intestine, a reduction in the jejunal and ileal mucosa, and a decrease in the total thickness of the ileum. Additionally, there may be a reduction in the number of villi per area in these organs and a thinning of the muscular layer in the large intestine. The structural changes induced by the maternal high-fat diet seem to reduce the stomach’s sensitivity to ethanol-induced ulcers, which is the only functional alteration observed. Therefore, the offspring of dams exposed to high-fat diets during pregnancy and lactation exhibits impaired gastrointestinal development, with alterations depending on dietary fat content and specific gastrointestinal regions. Structural changes did not always result in functional abnormalities and, in some cases, appeared protective. The long-term consequences of the observed morphological alterations require further investigation.

Keywords

Maternal high-fat dietoffspringgastrointestinal changesWistar rats

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Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 15 , 2024 , e33
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Copyright
© The Author(s), 2024. Published by Cambridge University Press in association with The International Society for Developmental Origins of Health and Disease (DOHaD)

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References

Aguila, MB, Pinheiro Ada, R, Parente, LB, Mandarim-de-Lacerda, CA. Dietary effect of different high fat diet on rat liver stereology. Liver Int. 2003; 23, 363–370.CrossRefGoogle ScholarPubMed
Ainge, H, Thompson, C, Ozanne, SE, Rooney, KB. A systematic review on animal models of maternal high fat feeding and offspring glycaemic control. Int J Obes. 2011; 35, 325–335.CrossRefGoogle ScholarPubMed
Alfaradhi, MZ, Ozanne, SE. Developmental programming in response to maternal overnutrition. Front Genet. 2011; 2, 27.CrossRefGoogle ScholarPubMed
Anitha, M, Reichardt, Fçois, Tabatabavakili, S, Nezami, BG, Chassaing, B, Mwangi, S, Vijay-Kumar, M, Gewirtz, A, Srinivasan, S. Intestinal dysbiosis contributes to the delayed gastrointestinal transit in high-fat diet fed mice. Cell Mol Gastroenterol Hepatol. 2016; 2, 328–339.CrossRefGoogle Scholar
Bertrand, RL, Senadheera, S, Tanoto, A, Tan, KL, Howitt, L, Chen, H, Murphy, TV, Sandow, SL, Liu, L, Bertrand, PP. Serotonin availability in rat colon is reduced during a Western diet model of obesity. Am J Physiol Gastrointest Liver Physiol. 2012; 303, G424–G434.CrossRefGoogle Scholar
Burgueño, AL, Cabrerizo, R, Gonzales Mansilla, N, Sookoian, S, Pirola, CJ. Maternal high-fat intake during pregnancy programs metabolic- syndrome-related phenotypes through liver mitochondrial DNA copy number and transcriptional activity of liver PPARGC1A. J Nutr Biochem. 2013; 24, 6–13.CrossRefGoogle ScholarPubMed
Camilleri, M, Malhi, H, Acosta, A. Gastrointestinal complications of obesity. Gastroenterology. 2017; 152, 1656–1670.CrossRefGoogle ScholarPubMed
Castañeda-Gutiérrez, E, Pouteau, E, Pescia, G, Moulin, J, Aprikian, O, Macé, K. The guinea pig as a model for metabolic programming of adiposity. Am J Clin Nutr. 2011; 94, 1838S–1845S.CrossRefGoogle Scholar
Cerf, ME, Louw, J, Herrera, E. High fat diet exposure during fetal life enhances plasma and hepatic omega-6 fatty acid profiles in fetal wistar rats. Nutrients. 2015; 7, 7231–7241.CrossRefGoogle ScholarPubMed
Charlton, M. Nonalcoholic fatty liver disease: a review of current understanding and future impact. Clin Gastroenterol Hepatol. 2004; 2, 1048–1058.CrossRefGoogle ScholarPubMed
Che, L, Liu, P, Yang, Z, Che, L, Hu, L, Qin, L, Wang, R, Fang, Z, Lin, Y, Xu, S, Feng, B, Li, J, Wu, D. Maternal high fat intake affects the development and transcriptional profile of fetal intestine in late gestation using pig model. Lipids Health Dis. 2016; 15, 90.CrossRefGoogle ScholarPubMed
Chowdhury, SS, Lecomte, V, Erlich, JH, Maloney, CA, Morris, MJ. Paternal high fat diet in rats leads to renal accumulation of lipid and tubular changes in adult offspring. Nutrients. 2016; 8, 521.CrossRefGoogle ScholarPubMed
Delgado-Aros, S, Locke, GR, Camilleri, M, Talley, NJ, Fett, S, Zinsmeister, AR, Melton, LJ. Obesity is associated with increased risk of gastrointestinal symptoms: a population-based study. Am J Gastroenterol. 2004; 99, 1801–1806.CrossRefGoogle ScholarPubMed
de Paula-Simona, LA, de Fante, T, Figueiredo Fontana, M, Oliveira Borges, F, Torsoni, MA, Milanski, M, Velloso, LA, Souza Torsoni, A. Lipid overload during gestation and lactation can independently alter lipid homeostasis in offspring and promote metabolic impairment after new challenge to high-fat diet. Nutr Metab. 2017; 14, 16.CrossRefGoogle Scholar
Doherty, NS, Hancock, AA. Role of alpha-2 adrenergic receptors in the control of diarrhea and intestinal motility. J Pharmacol Experim Therap. 1983; 225, 269–274.Google ScholarPubMed
Duarte, ACGO, Fonseca, DF, Soave, CF Sene-Fiorese, M, Dâmaso, AR, Cheik, NC. Dieta hiperlipídica e capacidade secretória de insulina em ratos. Rev Nutr. 2006; 19, 341–348.CrossRefGoogle Scholar
Gallagher, TK, Geoghegan, JG, Baird, AW, Winter, DC. Implications of altered gastrointestinal motility in obesity. Obes Surg. 2007; 17, 1399–1407.CrossRefGoogle ScholarPubMed
Ganu, RS, Harris, RA, Collins, K, Aagaard, KM. Early origins of adult disease: Approaches for investigating the programmable epigenome in humans, nonhuman primates, and rodents. ILAR J. 2012; 53, 306–321.CrossRefGoogle ScholarPubMed
Glastras, SJ. Maternal obesity increases the risk of metabolic disease and impacts renal health in offspring. Bioscience Rep. 2018; 38, BSR20180050.CrossRefGoogle ScholarPubMed
Guilloteau, P, Zabielski, R, Hammon, HM, Metges, CC. Nutritional programming of gastrointestinal tract development. Is the pig a good model for man? Nutr Res Rev. 2010; 23, 4–22.CrossRefGoogle Scholar
Ha, M, Kim, VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol. 2014; 15, 509–524.CrossRefGoogle ScholarPubMed
Hans-Rudolph, B, Klein, S. Advances in obesity: causes, consequences, and therapy. Gastroenterology. 2017; 152, 1635–1637.Google Scholar
Harrison, AP, Erlwanger, KH, Elbrønd, VS, Andersen, NK, Unmack, MA. Gastrointestinal tract models and techniques for use in safety pharmacology. J Pharmacol Toxicol Methods. 2004; 49, 187–199.CrossRefGoogle ScholarPubMed
Heerwagen, MJ, Miller, MR, Barbour, LA, Friedman, JE. Maternal obesity and fetal metabolic programming: a fertile epigenetic soil. Am J Physiol Regul Integr Comp Physiol. 2010; 299, R711–R722.CrossRefGoogle ScholarPubMed
Hildebrandt, MA, Hoffmann, C, Sherrill-Mix, SA, Keilbaugh, SA, Hamady, M, Chen, YY, Knight, R, Ahima, RS, Bushman, F, Wu, GD. High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology. 2009; 137, 1716–1724.CrossRefGoogle ScholarPubMed
Honoré, SM, Grande, MV, Gomez Rojas, J, Sánchez, SS. Smallanthus sonchifolius (Yacon) flour improves visceral adiposity and metabolic parameters in high-fat-diet-fed rats. J Obes. 2018; 2018, 1–15.CrossRefGoogle ScholarPubMed
Innis, SM, Dai, C, Wu, X, Buchan, AM, Jacobson, K. Perinatal lipid nutrition alters early intestinal development and programs the response to experimental colitis in young adult rats. Am J Physiol Gastrointest. Liver Physio. 2010; 299, G1376–G1385.CrossRefGoogle ScholarPubMed
Ishii, K, Kono, H, Hosomura, N, Tsuchiya, M, Ohgiku, M, Tanaka, N, Fujii, H. Medium-chain triglycerides enhance mucous secretion and cell proliferation in the rat. J Gastroenterol. 2009; 44, 204–211.CrossRefGoogle ScholarPubMed
Kim, YS, Ho, SB. Intestinal goblet cells and mucins in health and disease: recent insights and progress. Curr Gastroenterol Rep. 2010; 12, 319–330.CrossRefGoogle ScholarPubMed
Koslo, RJ, Burks, TF, Porreca, F. Centrally administered bombesin affects gastrointestinal transit and colonic bead expulsion through supraspinal mechanisms. J Pharmacol Exp Ther. 1986; 238, 62–67.Google ScholarPubMed
Leddy, MA, Power, ML, Schulkin, J. The impact of maternal obesity on maternal and fetal health. Rev Obstet Gynecol. 2008; 1, 170–178.Google ScholarPubMed
Liu, P, Che, L, Yang, Z, Feng, B, Che, L, Xu, S, Lin, Y, Fang, Z, Li, J, Wu, D. A maternal high-energy diet promotes intestinal development and intrauterine growth of offspring. Nutrients. 2016; 8, 258.CrossRefGoogle ScholarPubMed
Masuyama, H, Hiramatsu, Y. Effects of a high-fat diet exposure in utero on the metabolic syndrome-like phenomenon in mouse offspring through epigenetic changes in adipocytokine gene expression. Endocrinology. 2012; 153, 2823–2830.CrossRefGoogle ScholarPubMed
Mcmenamim, CA, Clyburn, C, Browning, KN. High fat diet during the perinatal period induces loss of myenteric nitrergic neurons and increases enteric glial density, prior to the development of obesity. Neuroscience. 2018; 393, 369–380.CrossRefGoogle Scholar
Meyer, AM, Neville, TL, Reed, JJ, Taylor, JB, Reynolds, LP, Redmer, DA, Hammer, CJ, Vonnahme, KA, Caton, JS. Maternal nutritional plane and selenium supply during gestation impact visceral organ mass and intestinal growth and vascularity of neonatal lamb offspring. J. Anim. Sci. 2013; 91, 2628–2639.CrossRefGoogle ScholarPubMed
Mortensen, ELK. Maternal preconceptional nutrition leads to variable fat deposition and gut dimensions of adult offspring mice (C57BL/6JBom). Int J Obesity. 2010; 34, 1618–1624.CrossRefGoogle ScholarPubMed
Navarrete, J, VÁSQUEZ, B, Del-Sol, M. Morphoquantitative analysis of the ileum of C57BL/6 mice (Mus musculus) fed with a high-fat diet. Int J Clin Exp Pathol. 2015; 8, 4649–14657.Google ScholarPubMed
Nezami, BG, Mwangi, SM, Lee, JE et al. MicroRNA 375 Mediates palmitate-induced enteric neuronal damage and high-fat diet-induced delayed intestinal transit in mice. Gastroenterology. 2014; 146, 473–483.e3.CrossRefGoogle ScholarPubMed
Ornellas, F, Souza-Mello, V, Mandarim-de-Lacerda, CA, Aguila, MB. Programming of obesity and comorbidities in the progeny: lessons from a model of diet-induced obese parents. PLoS One. 2015; 10, e0124737.CrossRefGoogle Scholar
Prado, LCda S, Silva, DB, Oliveira-Silva, GLde, Hiraki, KRN, Canabrava, HAN, Bispo-da-Silva, LB. The gastroprotective effects of Eugenia dysenterica (Myrtaceae) leaf extract: the possible role of condensed tannins. Biol Pharm Bull. 2014; 37, 722–730.CrossRefGoogle ScholarPubMed
Racusen, LC, Binder, HJ. Ricinoleic acid stimulation of active anion secretion in colonic mucosa of the rat. J Clin Invest. 1979; 63, 743–749.CrossRefGoogle ScholarPubMed
Rezende, LP, Fortunato Silva, J, da Costa, VAA, Bispo da Silva, LB, Balbi, APC. Effects of maternal hypothyroidism in the gastrointestinal system of male young offspring from wistar rats. J Dev Orig Health Dis. 2021; 12, 286–292.CrossRefGoogle ScholarPubMed
Robert, A, Nezamis, JE, Lancaster, C, Hanchar, AJ, Klepper, MS. Enteropooling assay: a test for diarrhea produced by prostaglandins. Prostaglandins. 1976; 11, 809–828.CrossRefGoogle ScholarPubMed
Ross, MG, Desai, M. Developmental programming of offspring obesity, adipogenesis, and appetite. Clin Obstet Gynecol. 2013; 56, 529–536.CrossRefGoogle ScholarPubMed
Rottiers, V, Naar, AM. MicroRNAs in metabolism and metabolic disorders. Nat Rev Mol Cell Biol. 2012; 13, 239–250.CrossRefGoogle ScholarPubMed
Ruehl-Fehlert, C, Kittle, B, Morawietz, G et al.. Revised guides for organ sampling and trimming in rats and mice – part 1: A joint publication of the RITA 1 and NACAD 2 groups. Experim Toxicol Pathol. 2003; 55(2-3), 91–106.CrossRefGoogle Scholar
Samuelsson, AM, Matthews, PA, Argenton, M, Christie, MR, McConnell, JM, Jansen, EH, Piersma, AH, Ozanne, SE, Twinn, DF, Remacle, C, Rowlerson, A, Poston, L, Taylor, PD. Diet-induced obesity in female mice leads to offspring hyperphagia, adiposity, hypertension, and insulin resistance: a novel murine model of developmental programming. Hypertension. 2008; 51, 383–392.CrossRefGoogle ScholarPubMed
Sangild, PT. Gut responses to enteral nutrition in preterm infants and animals. Exp. Biol Med. 2006; 231, 1695–1711.CrossRefGoogle ScholarPubMed
Slupecka-Ziemilska, M, Grzesiak, P, Kowalczyk, P, Wychowański, P, Woliński, J. Maternal high-fat diet exposure during gestation and lactation affects intestinal development in suckling rats. Front Physiol. 2021; 12, 1–10.CrossRefGoogle ScholarPubMed
Soares, A, Beraldi, EJ, Ferreira, PE, Bazotte, RB, Buttow, NC. Intestinal and neuronal myenteric adaptations in the small intestine induced by a high-fat diet in mice. BMC Gastroenterolog. 2015; 15, 3.CrossRefGoogle ScholarPubMed
Spencer, JA, Chang, TC, Jones, J, Robson, SC, Preece, MA. Third trimester fetal growth and umbilical venous blood concentrations of IGF-1, IGFBP-1, and growth hormone at term. Arch Dis Child Fetal Neonatal Ed. 1995; 73, F87–F90.CrossRefGoogle ScholarPubMed
Sukhotnik, I, Mor-Vaknin, N, Drongowski, RA, Miselevich, I, Coran, AG, Harmon, CM. Effect of dietary fat on early morphological intestinal adaptation in a rat with short bowel syndrome. Pediatr Surg Int. 2004; 20, 419–424.CrossRefGoogle Scholar
Tenenbaum-Gavish, K, Hod, M. Impact of maternal obesity on fetal health. Fetal Diagn Ther. 2013; 34, 1–7.CrossRefGoogle ScholarPubMed
Tramonte, R, Carvalho, ROM, Farias, DC, Serafim, JDM, Ortellado, DK, d’Acampora, AJ. Alterações da mucosa intestinal em ratos: estudo morfométrico em três diferentes tratamentos após indução experimental de sepse abdominal aguda. Acta Cirúrgica Brasileira. 2004; 19, 120–125.CrossRefGoogle Scholar
Tunaru, S, Althoff, TF, Nüsing, RM, Diener, M, Offermanns, S. Castor oil induces laxation and uterus contraction via ricinoleic acid active/ting prostaglandin EP3 receptors. Proc Natl Acad Sci USA. 2012; 109, 9179–9184.CrossRefGoogle Scholar
Uddin, SJ, Shilpi, JA, Alam, SM, Alamgir, M, Rahman, MT, Sarker, SD. Antidiarrhoeal activity of methanol extract of the barks of Xylocarpus moluccenis in castor oil and magnesium sulphate-induced diarrhea models in mice. J Ethnopharmacol. 2005; 101, 139–143.CrossRefGoogle ScholarPubMed
Vigueras, RM, Rojas-Castañeda, J, Hernández, R, Reyes, G, Alvarez, C. Histological characteristics of the intestinal mucosa of the rat during the first year of life. Lab Anim. 1999; 33, 393–400.CrossRefGoogle Scholar
Watson, WC, Gordon, RS Jr. Studies on the digestion, absorption and metabolism of castor oil. Biochem Pharmacol. 1962; 11, 229–236.CrossRefGoogle ScholarPubMed
Whitaker, RC, Wright, JA, Pepe, MS, Seidel, KD, Dietz, WH. Predicting obesity in young adulthood from childhood and parental obesity. N Engl J Med. 1997; 337, 869–873.CrossRefGoogle Scholar
Williams, L, Seki, Y, Vuguin, PM, Charron, MJ. Animal models of in utero exposure to a high fat diet: a review. Biochim Biophys Acta. 2014; 1842, 507–519.CrossRefGoogle ScholarPubMed
Wisen, O, Hellstrom, PM. Gastrointestinal motility in obesity. J Intern Med. 1995; 237, 411–418.CrossRefGoogle ScholarPubMed
Zambrano, E, Bautista, CJ, Deas, M, Martinez-Samayoa, PM, Gonzalez-Zamorano, M, Ledesma, H, Morales, J, Larrea, F, Nathanielsz, PW. A low maternal protein diet during pregnancy and lactation has sex- and window of exposure-specific effects on offspring growth and food intake, glucose metabolism and serum leptin in the rat. J Physiol. 2006; 571, 221–230.CrossRefGoogle ScholarPubMed
Zambrano, E, Martínez-Samayoa, PM, Rodríguez-González, GL, Nathanielsz, PW. Dietary intervention prior to pregnancy reverses metabolic programming in male offspring of obese rats. J Physiol. 2010; 588, 1791–1799.CrossRefGoogle ScholarPubMed
Zheng, J, Xiao, X, Zhang, Q, Yu, M, Xu, J, Wang, Z. Maternal high-fat diet modulates hepatic glucose, lipid homeostasis and gene expression in the PPAR pathway in the early life of offspring. Int J Mol Sci. 2014; 15, 14967–14983.CrossRefGoogle ScholarPubMed