DHA-rich n-3 PUFAs intake from the early- and mid-pregnancy decreases the weight gain by affecting the DNA methylation status among Chinese Han infants

  • Ping Li Laboratory of Nutrition and Development, Key Laboratory of Major Disease in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
  • Xiaoyu Chen Laboratory of Nutrition and Development, Key Laboratory of Major Disease in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
  • Tianyi Teng Laboratory of Nutrition and Development, Key Laboratory of Major Disease in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
  • Xiuqin Fan Laboratory of Nutrition and Development, Key Laboratory of Major Disease in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
  • Tiantian Tang Laboratory of Nutrition and Development, Key Laboratory of Major Disease in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
  • Rui Wang Laboratory of Nutrition and Development, Key Laboratory of Major Disease in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
  • Yurong Zhao Department of Obstetrics and Gynecology, Fuxing Hospital, Capital Medical University, Beijing, China
  • Kemin Qi Laboratory of Nutrition and Development, Key Laboratory of Major Disease in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
DOI: https://doi.org/10.29219/fnr.v65.7548
Keywords: Docosahexaenoic acid; n-3 polyunsaturated fatty acids; pregnancy; body mass index; methylation; obesity-related genes.

Abstract

Background: Maternal exogenous docosahexaenoic acid (DHA)-rich n-3 polyunsaturated fatty acids (PUFAs) intake during the pregnancy, especially DHA, has inconsistent effects on reducing the fat storage of the infants in different clinical studies.

Objectives: We sought to determine the effects of maternal exogenous DHA-rich n-3 PUFAs capsule intake from the different pregnancy periods on the weight gain of their infants through modifying the DNA methylation status of obesity-associated genes in the umbilical cord blood.

Design: A prospective 3-year follow-up study after the pregnancy was enrolled in this cohort from May to October 2016. They were divided into different groups according to the initial time of exogenous DHA capsule intake through the questionnaires (S1 – early trimester, S2 – mid-trimester, S3 – late trimester, and control – without). The concentrations and compositions of DHA were determined by gas chromatography. We applied quantitative DNA methylation states of the obesity-associated genes in the umbilical cord blood. The growth outcomes and relevant Z-scores were recorded at birth and 1 and 2 years. The correlations between DNA methylation status of the obesity-associated genes with the consents of DNA and body mass index (BMI) values were investigated as the measures.

Results: In total, 205 pregnant women and their infants were eligible for this follow-up study. The concentrations and compositions of DHA in the colostrum and umbilical cord blood were higher in the S1 and S2 groups than those in the control and S3 groups as well as the decreased weight, BMI, weight for age Z-score (WAZ) and BMI for age Z-score (BMI Z) at birth and 1 and/or 2 years, and higher levels of global DNA methylation and many CpG sites in the obesity-associated genes, such as CpG2, CpG9, CpG11, and CpG16 of PPAR-γ; CpG2,3, CpG4-6, CpG8, CpG9,10, CpG11, CpG15,16, and average of CCAAT/enhancer binding protein α (C/EBP-α); CpG1 and average of adiponectin; CpG1, CpG2, CpG3, CpG5, CpG6, CpG7, and average of insulin-like growth factor 2 (IGF-2); CpG6, CpG7, CpG9, CpG16, CpG23, and CpG24 of leptin, which were more obvious in the S1 group when compared with those in the S2 group. These above hypermethylation levels of CpG sites were negatively correlated with the BMI and positively related with the changes of DHA in the colostrum and umbilical cord blood.

Conclusions: Maternal exogenous DHA-rich n-3 PUFAs intake from early- and mid- trimesters of the pregnancy may avoid the development of obesity among Chinese Han infants until 2 years by modulating DNA methylation states of obesity-associated genes, which could provide attractive targets for prenatal prevention of the metabolic disorders.

Downloads

Download data is not yet available.

References


  1. Wang YC, McPherson K, Marsh T, Gortmaker SL, Brown M. Health and economic burden of the projected obesity trends in the USA and the UK. Lancet 2011; 378(9793): 815–25. doi: 10.1016/S0140-6736(11)60814-3
  2. Yazdi FT, Clee SM, Meyre D. Obesity genetics in mouse and human: back and forth and back again. Peer J 2015; 3: e856. doi: 10.7717/peerj.856
  3. Marangoni F, Cetin I, Verduci E, Canzone G, Giovannini M, Scollo P, et al. Maternal diet and nutrient requirements in pregnancy and breastfeeding: an Italian consensus document. Nutrients 2016; 8(10): 629. doi: 10.3390/nu8100629
  4. Adair LS. Long-term consequences of nutrition and growth in early childhood and possible preventive interventions. Nestle Nutr Inst Workshop Ser 2014; 78: 111–20. doi: 10.1159/000354949
  5. Berti C, Cetin I, Agostoni C, Desoye G, Devlieger R, Emmett PM, et al. Pregnancy and infants’ outcome: nutritional and metabolic implications. Crit Rev Food Sci Nutr 2016; 56(1): 82–91. doi: 10.1080/10408398.2012.745477
  6. Muhlhausler BS, Gugusheff JR, Ong ZY, Vithayathil MA. Nutritional approaches to breaking the intergenerational cycle of obesity. Can J Physiol Pharmacol 2013; 91(6): 421–8. doi: 10.1139/cjpp-2012-0353
  7. Muhlhausler BS, Gibson RA, Makrides M. Effect of long-chain polyunsaturated fatty acid supplementation during pregnancy or lactation on infant and child body composition: a systematic review. Am J Clin Nutr 2010; 92(4): 857–63. doi: 10.3945/ajcn.2010.29495
  8. Li P, Tang T, Chang X, Fan X, Chen X, Wang R, et al. Abnormality in maternal dietary calcium intake during pregnancy and lactation promotes body weight gain by affecting the gut microbiota in mouse offspring. Mol Nutr Food Res 2019; 63(5): e1800399. doi: 10.1002/mnfr.201800399
  9. Mozaffarian D, Rimm EB. Fish intake contaminants and human health: evaluating the risks and the benefits. JAMA 2006; 296(15): 1885–99. doi: 10.1001/jama.296.15.1885
  10. Nishimura RY, Barbieiri P, de Castro GS, Jordão AA, Jr, Perdoná GdS, Sartorelli DS. Dietary polyunsaturated fatty acid intake during late pregnancy affects fatty acid composition of mature breast milk. Nutrition 2014; 30(6): 685–9. doi: 10.1016/j.nut.2013.11.002
  11. Innis SM, Friesen RW. Essential n-3 fatty acids in pregnant women and early visual acuity maturation in term infants. Am J Clin Nutr 2008; 87(3): 548–57. doi: 10.1093/ajcn/87.3.548
  12. Jiao J, Li Q, Chu J, Zeng W, Yang M, Zhu S. Effect of n-3 PUFA supplementation on cognitive function throughout the life span from infancy to old age: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr 2014; 100(6): 1422–36. doi: 10.3945/ajcn.114.095315
  13. Muhlhausler BS, Yelland LN, McDermott R, Tapsell L, McPhee A, Gibson RA, et al. DHA supplementation during pregnancy does not reduce BMI or body fat mass in children: follow-up of the DHA to Optimize Mother Infant Outcome randomized controlled trial. Am J Clin Nutr 2016; 103(6): 1489–96. doi: 10.3945/ajcn.115.126714
  14. Huang CW, Chien YS, Chen YJ, Ajuwon KM, Mersmann HM, Ding ST. Role of n-3 polyunsaturated fatty acids in ameliorating the obesity-induced metabolic syndrome in animal models and humans. Int J Mol Sci 2016; 17(10): 1689. doi: 10.3390/ijms17101689
  15. Calder PC. Omega-3 fatty acids and inflammatory processes: from molecules to man. Biochem Soc Trans 2017; 45(5): 1105–15. doi: 10.1042/BST20160474
  16. Healy-Stoffel M, Levant B. N-3 (Omega-3) fatty acids: effects on brain dopamine systems and potential role in the etiology and treatment of neuropsychiatric disorders. CNS Neurol Disord Drug Targets 2018; 17(3): 216–32. doi: 10.2174/1871527317666180412153612
  17. Cash HL, McGarvey ST, Houseman EA, Marsit CJ, Hawley NL, Lambert-Messerlian GM, et al. Cardiovascular disease risk factors and DNA methylation at the LINE-1 repeat region in peripheral blood from Samoan Islanders. Epigenetics 2011; 6(10): 1257–64. doi: 10.4161/epi.6.10.17728
  18. Kim M, Long T, Arakawa K, Wang R, Yu MC, Laird PW. DNA methylation as a biomarker for cardiovascular disease risk. PLoS One 2010; 5(3): e9692. doi: 10.1371/journal.pone.0009692
  19. van Dijk SJ, Molloy PL, Varinli H, Morrison JL, Muhlhausler BS, Members of EpiSCOPE. Epigenetics and human obesity. Int J Obes (Lond) 2015; 39(2): 85–97. doi: 10.1038/ijo.2014.34
  20. Wang X, Zhu H, Snieder H, Su S, Munn D, Harshfield G, et al. Obesity related methylation changes in DNA of peripheral blood leukocytes. BMC Med 2010; 8: 87. doi: 10.1186/1741-7015-8-87
  21. Dominguez SP, Cox SE, Prentice AM, Hennig BJ, Moore SE. Maternal nutritional status C(1) metabolism and offspring DNA methylation: a review of current evidence in human subjects. Proc Nutr Soc 2012; 71(1): 154–65. doi: 10.1017/S0029665111003338
  22. Karimi M, Vedin I, Freund Levi Y, Basun H, Faxén Irving G, Eriksdotter M, et al. DHA-rich n-3 fatty acid supplementation decreases DNA methylation in blood leukocytes: the OmegAD study. Am J Clin Nutr 2017; 106(4): 1157–65. doi: 10.3945/ajcn.117.155648
  23. Tian C, Fan C, Liu X, Xu F, Qi K. Brain histological changes in young mice submitted to diets with different ratios of n-6/n-3 polyunsaturated fatty acids during maternal pregnancy and lactation. Clin Nutr 2011; 30(5): 659–67. doi: 10.1016/j.clnu.2011.03.002
  24. Hu G, Li P, Cui X, Li Y, Zhang J, Zhai X, et al. Cr(VI)-induced methylation and down-regulation of DNA repair genes and its association with markers of genetic damage in workers and 16HBE cells. Environ Pollut 2018; 238: 833–43. doi: 10.1016/j.envpol.2018.03.046
  25. Shen W, Wang C, Xia L, Fan C, Dong H, Deckelbaum RJ, et al. Epigenetic modification of the leptin promoter in diet-induced obese mice and the effects of N-3 polyunsaturated fatty acids. Sci Rep 2014; 4: 5282. doi: 10.1038/srep05282
  26. Koletzko B, Agostoni C, Bergmann R, Ritzenthaler K, Shamir R. Physiological aspects of human milk lipids and implications for infant feeding: a workshop report. Acta Paediatr 2011; 100(11): 1405–15. doi: 10.1111/j.1651-2227.2011.02343.x
  27. Koletzko B, Lien E, Agostoni C, Böhles H, Campoy C, Cetin I, et al. The roles of long-chain polyunsaturated fatty acids in pregnancy lactation and infancy: review of current knowledge and consensus recommendations. J Perinat Med 2008; 36(1): 5–14. doi: 10.1515/JPM.2008.001
  28. Arterburn LM, Hall EB, Oken H. Distribution interconversion and dose response of n-3 fatty acids in humans. Am J Clin Nutr 2006; 83(6 Suppl): 1467S–76S. doi: 10.1093/ajcn/83.6.1467S
  29. Brenna JT, Varamini B, Jensen RG, Diersen-Schade DA, Boettcher JA, Arterburn LM. Docosahexaenoic and arachidonic acid concentrations in human breast milk worldwide. Am J Clin Nutr 2007; 85(6): 1457–64. doi: 10.1093/ajcn/85.6.1457
  30. Maslova E, Rifas-Shiman SL, Olsen SF, Gillman MW, Oken E. Prenatal n-3 long-chain fatty acid status and offspring metabolic health in early and mid-childhood: results from Project Viva. Nutr Diabetes 2018; 8(1): 29. doi: 10.1038/s41387-018-0040-2
  31. Hibbeln JR, Davis JM, Steer C, Emmett P, Rogers I, Williams C, et al. Maternal seafood consumption in pregnancy and neurodevelopmental outcomes in childhood: an observational cohort study. Lancet 2007; 369(9561): 578–85. doi: 10.1016/S0140-6736(07)60277-3
  32. Valli V, Heilmann K, Danesi F, Bordoni A, Gerhäuser C. Modulation of adipocyte differentiation and proadipogenic gene expression by sulforaphane genistein and docosahexaenoic acid as a first step to counteract obesity. Oxid Med Cell Longev 2018; 2018: 1617202. doi: 10.1155/2018/1617202
  33. Kadakia R, Josefson J. The relationship of insulin-like growth factor 2 to fetal growth and adiposity. Horm Res Paediatr 2016; 85(2): 75–82. doi: 10.1159/000443500
  34. Zhang DL, Du Q, Djemli A, Julien P, Fraser WD, Luo ZC. Cord blood insulin IGF-I IGF-II leptin adiponectin and ghrelin and their associations with insulin sensitivity β-cell function and adiposity in infancy. Diabet Med 2018; 35(10): 1412–9. doi: 10.1111/dme.13671
  35. Wang X, Cao Q, Yu L, Shi H, Xue B, Shi H. Epigenetic regulation of macrophage polarization and inflammation by DNA methylation in obesity. JCI Insight 2016; 1(19): e87748. doi: 10.1172/jci.insight.87748
  36. Nawathe AR, Christian M, Kim SH, Johnson M, Savvidou MD, Terzidou V. Insulin-like growth factor axis in pregnancies affected by fetal growth disorders. Clin Epigenetics 2016; 8: 11. doi: 10.1186/s13148-016-0178-5
  37. Moseti D, Regassa A, Kim WK. Molecular regulation of adipogenesis and potential anti-adipogenic bioactive molecules. Int J Mol Sci 2016; 17(1): 124. doi: 10.3390/ijms17010124
  38. García-Robles R, Ayala-Ramirez PA, Perdomo-Velásquez SA. Epigenética: definición bases moleculares implicaciones en la salud y en la evolución humana. Rev Ciencias Salud 2012; 10(1): 59–71.
  39. Corella D, Ordovas JM. Basic concepts in molecular biology related to genetics and epigenetics. Rev Esp Cardiol (Engl Ed) 2017; 70(9): 744–53. doi: 10.1016/j.recesp.2017.02.034
  40. Martínez JA, Milagro FI, Claycombe KJ, Schalinske KL. Epigenetics in adipose tissue obesity weight loss and diabetes. Adv Nutr 2014; 5(1): 71–81. doi: 10.3945/an.113.004705
  41. Handy DE, Castro R, Loscalzo J. Epigenetic modifications: basic mechanisms and role in cardiovascular disease. Circulation 2011; 123(19): 2145–56. doi: 10.1161/CIRCULATIONAHA.110.956839
  42. Kulkarni A, Dangat K, Kale A, Sable P, Chavan-Gautam P, Joshi S. Effects of altered maternal folic acid vitamin B12 and docosahexaenoic acid on placental global DNA methylation patterns in Wistar rats. PLoS One 2011; 6(3): e17706. doi: 10.1371/journal.pone.0017706
  43. Burdge GC, Lillycrop KA. Fatty acids and epigenetics. Curr Opin Clin Nutr Metab Care 2014; 17(1): 156–61. doi: 10.1097/MCO.0000000000000023
  44. Meher A, Joshi A, Joshi S. Differential regulation of hepatic transcription factors in the Wistar rat offspring born to dams fed folic acid vitamin B12 deficient diets and supplemented with omega-3 Fatty acids. PLoS One 2014; 9(2): e90209. doi: 10.1371/journal.pone.0090209
  45. Voisin S, Almén MS, Moschonis G, Chrousos GP, Manios Y, Schiöth HB. Dietary fat quality impacts genome-wide DNA methylation patterns in a cross sectional study of Greek preadolescents. Eur J Hum Genet 2014; 23(5): 654–62. doi: 10.1038/ejhg.2014.139
  46. Hoile SP, Clarke HR, Huang RC, Calder PC, Mori TA, Beilin LJ, et al. Supplementation with N-3 long-chain polyunsaturated fatty acids or olive oil in men and women with renal disease induces differential changes in the DNA methylation of FADS2 and ELOVL5 in peripheral blood mononuclear cells. PLoS One 2014; 9(10): e109896. doi: 10.1371/journal.pone.0109896
  47. Dominguez SP, Moore SE, Baker MS, Bergen AW, Cox SE, Dyer RA, et al. Maternal nutrition at conception modulates DNA methylation of human metastable epialleles. Nat Commun 2014; 5: 3746. doi: 10.1038/ncomms4746
  48. Tobi EW, Goeman JJ, Monajemi R, Gu H, Putter H, Zhang Y, et al. DNA methylation signatures link prenatal famine exposure to growth and metabolism. Nat Commun 2014; 5: 5592. doi: 10.1038/ncomms6592
Published
2021-10-07
How to Cite
Li P., Chen X., Teng T., Fan X., Tang T., Wang R., Zhao Y., & Qi K. (2021). DHA-rich n-3 PUFAs intake from the early- and mid-pregnancy decreases the weight gain by affecting the DNA methylation status among Chinese Han infants. Food & Nutrition Research, 65. https://doi.org/10.29219/fnr.v65.7548
Issue
Vol 65 (2021)
Section
Original Articles
Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors retain copyright of their work, with first publication rights granted to SNF Swedish Nutrition Foundation. Read the full Copyright- and Licensing Statement.

 

 

Crossref
Scopus
Google Scholar
Europe PMC