Palabras clave
Epigenética
Desarrollo fetal
Enfermedad de hígado graso no alcohólico
Metilación de ADN
Cómo citar
Resumen
La enfermedad de hígado graso no alcohólico pediátrica está relacionada con los eventos adversos del embarazo que promueven en el feto una modulación de los procesos de metilación diferencial. El objetivo de la presente investigación fue revisar la información existente aportada por investigaciones sobre procesos de metilación diferencial que ocurren en la programación fetal y que son regulados por la exposición a la obesidad gestacional. Se realizó una revisión en la base de datos PubMed con la inclusión de ensayos clínicos aleatorizados, revisiones sistemáticas y revisiones de tema, relacionados con los procesos de metilación que predisponen a enfermedad de hígado graso no alcohólico en edades tempranas por exposición fetal a obesidad materna. La evidencia reporta cambios significativos de los procesos de metilación diferencial en la expresión genética de los hijos de madres con obesidad. Estos cambios tienen una capacidad importante de programar una predisposición al desarrollo de esta patología.
Referencias
Younossi ZM, Golabi P, Paik JM, Henry A, Van Dongen C, Henry L. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review. Hepatology. 2023;77(4):1335–47.
Jarvis H, Craig D, Barker R, Spiers G, Stow D, Anstee QM, et al. Metabolic risk factors and incident advanced liver disease in non-alcoholic fatty liver disease (NAFLD): A systematic review and meta-analysis of population-based observational studies. PLoS Med. 2020;17(4):e1003100.
Anderson EL, Howe LD, Jones HE, Higgins JP, Lawlor DA, Fraser A. The Prevalence of NonAlcoholic Fatty Liver Disease in Children and Adolescents: A Systematic Review and MetaAnalysis. PLoS One.2015;10(10):e0140908.
Alisi A, Manco M, Vania A, Nobili V. Pediatric nonalcoholic fatty liver disease in 2009. J Pediatr. 2009;155(4):469–474.
Flores J, Gómez R, Rodríguez G, Morán S. P0223 Prevalence of Nonalcoholic Steatohepatitis (NASH) in Mexican Children of An Elementary School. J Pediatr Gastroenterol Nutr. 2004;39:p S143.
Schwimmer JB, McGreal N, Deutsch R, Finegold MJ, Lavine JE. Influence of gender, race, and ethnicity on suspected fatty liver in obese adolescents. Pediatrics. 2005; 115(5):e561–e565.
Buzzetti E, Pinzani M, Tsochatzis EA. The multiplehit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism. 2016;65(8):1038– 1048.ui
Kobyliak N, Abenavoli L, Mykhalchyshyn G, Kononenko L, Boccuto L, Kyriienko D, et al. A Multi-strain Probiotic Reduces the Fatty Liver Index, Cytokines and Aminotransferase levels in NAFLD Patients: Evidence from a Randomized Clinical Trial. J Gastrointestin Liver Dis. 2018 ;27(1):41–49.
Rahmanabadi A, Mahboob S, Amirkhizi F, Hosseinpour-Arjmand S, Ebrahimi-Mameghani M. Oral α-lipoic acid supplementation in patients with non-alcoholic fatty liver disease: effects on adipokines and liver histology features. Food Funct. 2019;10(8):4941–4952.
Choudhary NS, Duseja A. Genetic and epigenetic disease modifiers: non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). Transl Gastroenterol Hepatol. 2021;6:2.
Güiza F, Vanhorebeek I, Verstraete S, Verlinden I, Derese I, Ingels C, et al. Effect of early parenteral nutrition during paediatric critical illness on DNA methylation as a potential mediator of impaired neurocognitive development: a pre-planned secondary analysis of the PEPaNIC international randomised controlled trial. Lancet Respir Med. 2020;8(3):288–303.
Zhou D, Wang H, Cui H, Chen H, Pan Y-X. Early-life exposure to high-fat diet may predispose rats to gender-specific hepatic fat accumulation by programming Pepck expression. J Nutr Biochem. 2015;26(5):433-440.
Godfrey KM, Costello PM, Lillycrop KA. Development, Epigenetics and Metabolic Programming. Nestle Nutr Inst Workshop Ser. 2016;85:71-80.
Brumbaugh DE, Tearse P, Cree-Green M, Fenton LZ, Brown M, Scherzinger A, et al. Intrahepatic fat is increased in the neonatal offspring of obese women with gestational diabetes. J Pediatr. 2013;162(5):930-936.
Bellatorre A, Scherzinger A, Stamm E, Martinez M, Ringham B, Dabelea D. Fetal Overnutrition and Adolescent Hepatic Fat Fraction: the Exploring Perinatal Outcomes in Children Study. J Pediatr. 2018;192:165-170.
Ayonrinde OT, Oddy WH, Adams LA, Mori TA, Beilin LJ, de Klerk N, et al. Infant nutrition and maternal obesity influence the risk of nonalcoholic fatty liver disease in adolescents. J Hepatol. 2017;67(3):568–576.
Ayonrinde OT, Adams LA, Mori TA, Beilin LJ, de Klerk N, Pennell CE, et al. Sex differences between parental pregnancy characteristics and nonalcoholic fatty liver disease in adolescents. Hepatology. 2018;67(1):108–122.
Schwimmer JB, Behling C, Newbury R, Deutsch R, Nievergelt C, Schork NJ, et al. Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology. 2005;42:641–649.
Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328–357.
Meffert PJ, Baumeister SE, Lerch MM, Mayerle J, Kratzer W, Völzke H. Development, external validation, and comparative assessment of a new diagnostic score for hepatic steatosis. Am J Gastroenterol. 2014;109(9):1404–1414.
Bedogni G, Bellentani S, Miglioli L, Masutti F, Passalacqua M, Castiglione A, et al. The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol. 2006;2:6:33.
American Health Organization. Obesity and overweight [Internet]. 2021 Jun 9 [citado 2021 Ago 5]. Disponible en: https://www.who.int/ news-room/fact-sheets/detail/obesity-andoverweight
Vitner D, Harris K, Maxwell C, Farine D. Obesity in pregnancy: a comparison of four national guidelines. J Matern Fetal Neonatal Med. 2019;32(15):2580–2590.
Barker DJ. In utero programming of chronic disease. Clin Sci (Lond). 1998;95(2):115–128.
Barker DJ. The Developmental Origins of Well-Being. Philos Trans R Soc Lond B Biol Sci. 2004;359(1449):1359-1366.
Miska EA, Ferguson-Smith AC. Transgenerational inheritance: Models and mechanisms of nonDNA sequence-based inheritance. Science. 2016;354(6308):59-63.
Zhang X, Asllanaj E, Amiri M, Portilla-Fernandez E, Bramer WM, Nano J, et al. Deciphering the role of epigenetic modifications in fatty liver disease: A systematic review. Eur J Clin Invest. 2021 May;51(5):e13479.
Crews D, Gillete R, Scarpino SV, Manikkam M, Savenkova MI, Skinner MK. Epigenetic transgenerational inheritance of altered stress responses. Proc. Natl Acad. Sci. USA. 2012; 109(23):9143–9148.
Padmanabhan N, Jia D, Geary-Joo C, Wu X, Ferguson-Smith AN, Fung E, et al. Mutation in folate metabolism causes epigenetic instability and transgenerational effects on development. Cell. 2013. 155(1), 81–93.
Zhang L, Lu Q, Chang C. Epigenetics in Health and Disease. Adv Exp Med Biol. 2020;1253:3–55.
Bestor TH, Edwards JR, Boulard M. Notes on the role of dynamic DNA methylation in mammalian development. Proc Natl Acad Sci USA. 2015;112(22):6796–6799.
Portela A., Esteller M. Epigenetic modifications and human disease. Nat. Biotechnol. 2010;28:1057–1068.
Lillycrop KA, Burdge GC. Epigenetic changes in early life and future risk of obesity. Int. J. Obes. (Lond). 2011;35(1):72-83.
Güiza F, Vanhorebeek I, Verstraete S, Verlinden I, Derese I, Ingels C, et al. Effect of early parenteral nutrition during paediatric critical illness on DNA methylation as a potential mediator of impaired neurocognitive development: a pre-planned secondary analysis of the PEPaNIC international randomised controlled trial. Lancet Respir Med. 2020;8(3):288–303.
Goto K, Numata M, Komura JI, Ono T, Bestor TH, Kondo H. Expression of DNA methyltransferase gene in mature and immature neurons as well as proliferating cells in mice. Differentiation. 1994;56(1-2):39–44.
Feng J, Chang H, Li E, Fan G. Dynamic expression of de novo DNA methyltransferases Dnmt3a and Dnmt3b in the central nervous system. J Neurosci Res. 2005;79(6):734–746.
Nan X, Meehan RR, Bird A. Dissection of the methyl-CpG binding domain from the chromosomal protein MeCP2. Nucleic Acids Res. 1993;21(21):4886–4892.
Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, et al. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature. 2009;462(7271):315–322.
Valinluck V, Sowers LC. Endogenous cytosine damage products alter the site selectivity of human DNA maintenance methyltransferase DNMT1. Cancer Res. 2007;67(3):946–950.
Hashimoto H, Liu Y, Upadhyay AK, Chang Y, Howerton SB, Vertino PM, et al. Recognition and potential mechanisms for replication and erasure of cytosine hydroxymethylation. Nucleic Acids Res. 2012;40(11):4841–4849.
Cao T, Pan W, Sun X, Shen H. Increased expression of TET3 predicts unfavorable prognosis in patients with ovarian cancer-a bioinformatics integrative analysis. J Ovarian Res. 2019;12(1):101.
Heijmans BT, Toby EW, Stein AD, Putter H, Blaw GJ, Susser ES, et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci USA. 2008;105(44):17046–17049.
Tobi EW, Lumey LH, Talens RP, Kremer D, Putter H, Stein AD, et al. DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific. Hum Mol Genet. 2009;18(21):4046–4053.
Modi N, Murgasova D, Ruager-Martin R, Thomas EL, Hyde MJ, Gale C, et al. The influence of maternal body mass index on infant adiposity and hepatic lipid content. Pediatr Res. 2011;70(3):287–291.
Herrera E, Amusquivar E. Lipid metabolism in the fetus and the newborn. Diabetes Metab Res Rev. 2000;16(3):202–210.
Frias AE, Morgan TK, Evans AE, Rasanen J, Oh KY, Thornburg KL, et al. Maternal high-fat diet disturbs uteroplacental hemodynamics and increases the frequency of stillbirth in a nonhuman primate model of excess nutrition. Endocrinology. 2011;152(6):2456–2464.
McCurdy CE, Bishop JM, Williams SM, Grayson BE, Smith MS, Friedman JE, et al. Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates. J Clin Invest. 2009;119(2):323–335.
Bruce KD, Cagampang FR, Argenton M, Zhang J, Ethirajan PL, Burdge GC, et al. Maternal highfat feeding primes steatohepatitis in adult mice offspring, involving mitochondrial dysfunction and altered lipogenesis gene expression. Hepatology. 2009;50(6):1796–1808.
Zhou D, Wang H, Cui H, Chen H, Pan YX. Early-life exposure to high-fat diet may predispose rats to gender-specific hepatic fat accumulation by programming Pepck expression. J Nutr Biochem. 2015;26(5):433–440.
Matsuzawa Nagata N, Takamura T, Ando H, Nakamura S, Kurita S, Misu H, et al. Increased oxidative stress precedes the onset of highfat diet-induced insulin resistance and obesity. Metabolism. 2008;57(8):1071–7.
McCurdy CE, Bishop JM, Williams SM, Grayson BE, Smith MS, Friedman JE, et al. Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates. J Clin Invest. 2009;119(2):323–35.
Reitman ML. Leptin in the Liver: A Toxic or Beneficial Mix?. Cell Metabolism. 2012;16(1):1-2.
Thorn SR, Baquero KC, Newsom SA, El Kasmi KC, Bergman BC, Shulman GI, et al. Early life exposure to maternal insulin resistance has persistent effects on hepatic NAFLD in juvenile nonhuman primates. Diabetes. 2014;63(8):2702–13.
Pruis MGM, Lendvai A, Bloks VW, Zwier MV, Baller JFW, de Bruin A, et al. Maternal western diet primes non-alcoholic fatty liver disease in adult mouse offspring. Acta Physiol. 2014;210(1):215–27.
Lowe WL Jr, Lowe LP, Kuang A, Catalano PM, Nodzenski M, Talbot O, et al. Maternal glucose levels during pregnancy and childhood adiposity in the Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study. Diabetologia. 2019;62(4):598–610.
Thorn SR, Baquero KC, Newsom SA, El Kasmi KC, Bergman BC, Shulman GI, et al. Early life exposure to maternal insulin resistance has persistent effects on hepatic NAFLD in juvenile nonhuman primates. Diabetes. 2014;63(8):2702–13.
Chen H, Morris MJ. Differential responses of orexigenic neuropeptides to fasting in offspring of obese mothers. Obesity. 2009;17(7):1356–62.
Chang G-Q, Gaysinskaya V, Karatayev O, Leibowitz SF. Maternal high-fat diet and fetal programming: increased proliferation of hypothalamic peptide-producing neurons that increase risk for overeating and obesity. J Neurosci. 2008;28(46):12107–19.
Johnson W, Choh AC, Soloway LE, Czerwinski SA, Towne B, Demerath EW. Eighty-year trends in infant weight and length growth: the Fels Longitudinal Study. J Pediatr. 2012;160(5):762–8.
Gaillard R, Steegers EA, Duijts L, Felix JF, Hofman A, Franco OH, et al. Childhood cardiometabolic outcomes of maternal obesity during pregnancy: the Generation R Study. . Hypertension. 2014;63(4):683-91.
Blomberg MI, Källén B. Maternal obesity and morbid obesity: the risk for birth defects in the offspring. Birth Defects Res A Clin Mol Teratol. 2010;88(1):35-40.
Sánchez CE, Barry C, Sabhlok A, Russell K, Majors A, Kollins SH, et al. Maternal pre-pregnancy obesity and child neurodevelopmental outcomes: a meta-analysis. Obes Rev. 2018;19(4):464–84.
Patro Golab B, Santos S, Voerman E, Lawlor DA, Jaddoe VWV, Gaillard R, et al. Influence of maternal obesity on the association between common pregnancy complications and risk of childhood obesity: an individual participant data meta-analysis. Lancet Child Adolesc Health. 2018;2(11):812–21.
Menting MD, Mintjens S, van de Beek C, Frick CJ, Ozanne SE, Limpens J, et al. Maternal obesity in pregnancy impacts offspring cardiometabolic health: Systematic review and meta-analysis of animal studies. Obes Rev. 2019;20(5):675–85.
Li L, Lagerberg T, Chang Z, Cortese S, Rosenqvist MA, Almqvist C, et al. Maternal pre-pregnancy overweight/obesity and the risk of attentiondeficit/hyperactivity disorder in offspring: a systematic review, meta-analysis and quasiexperimental family-based study. Int J Epidemiol. 2020;49(3):857–75.
Jansen MAC, Dalmeijer GW, Saldi SR, Grobbee DE, Baharuddin M, Uiterwaal CS, et al. Pre-pregnancy parental BMI and offspring blood pressure in infancy. Eur J Prev Cardiol. 2019;26(15):1581–90.
Oben JA, Mouralidarane A, Samuelsson A-M, Matthews PJ, Morgan ML, McKee C, et al. Maternal obesity during pregnancy and lactation programs the development of offspring nonalcoholic fatty liver disease in mice. J Hepatol. 2010;52(6):913–20.
Sharp GC, Salas LA, Monnereau C, Allard C, Yousefi P, Everson TM, et al. Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium. Hum Mol Genet. 2017;26(20):4067–4085.
Martin CL, Jima D, Sharp GC, McCullough LE, Park SS, Kowdy KM, et al. Maternal Pre-Pregnancy Obesity, Offspring Cord Blood DNA Methylation, and Offspring Cardiometabolic Health in Early Childhood: An Epigenome-Wide Association Study. Epigenetics. 2019;14(4):325–340.
Sharp GC, Lawlor DA, Richmond RC, Fraser A, Simpkin A, Suderman M, et al. Maternal prepregnancy BMI and gestational weight gain, offspring DNA methylation and later offspring adiposity: findings from the Avon Longitudinal Study of Parents and Children. Int J Epidemiol. 2015;44(4):1288–1304.
Nogues P, Dos Santos E, Jammes H, Berveiller P, Arnould L, Vialard F, et al. Maternal obesity influences expression and DNA methylation of the adiponectin and leptin systems in human third-trimester placenta. Clin Epigenetics. 2019;11(1):20.
Esta obra está bajo una licencia internacional Creative Commons Atribución 4.0.
Derechos de autor 2023 Médicas UIS