Hostname: page-component-cd9895bd7-8ctnn Total loading time: 0 Render date: 2024-12-28T05:00:50.109Z Has data issue: false hasContentIssue false
  • English
  • Français

Supplementation with methyl donors during lactation to high-fat-sucrose-fed dams protects offspring against liver fat accumulation when consuming an obesogenic diet

Published online by Cambridge University Press:  01 August 2014

P. Cordero ,
F. I. Milagro ,
J. Campion  and
J. A. Martinez
P. Cordero
Affiliation:
Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain
F. I. Milagro
Affiliation:
Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain
J. Campion
Affiliation:
Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain
J. A. Martinez*
Affiliation:
Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain
*
*Address for correspondence: Prof. J. Alfredo Martinez, Department of Nutrition, Food Science and Physiology, University of Navarra, Irunlarrea Street 1, 31008 Pamplona, Spain. Email:jalfmtz@unav.es
Get access Rights & Permissions [Opens in a new window]

Abstract

Methyl donor supplementation has been reported to prevent obesity-induced liver fat accumulation in adult rats. We hypothesized that this protection could be mediated by perinatal nutrition. For this purpose, we assessed the response to an obesogenic diet (high-fat-sucrose, HFS) during adulthood depending on maternal diet during lactation. Female Wistar rats fed control diet during pregnancy were assigned to four postpartum dietary groups: control, control supplemented with methyl donors (choline, betaine, folic acid, vitamin B12), HFS and HFS supplemented with methyl donors. At weaning, the male offspring was transferred to a chow diet and at week 12th assigned to a control or a HFS diet during 8 weeks. The offspring whose mothers were fed HFS during lactation showed increased adiposity (19%, P<0.001). When fed the HFS diet as adults, offspring whose mothers were HFS supplemented had more body fat (23%, P<0.001) than those from HFS non-supplemented. However, they showed lower liver fat accumulation (−18%, P<0.001). Srebf1, Dnmt1 and Lepr liver mRNA levels increased after adulthood HFS feeding. In those animals HFS fed during adulthood, previous maternal HFS decreased Lepr and Dnmt1 expression levels when compared with c-HFS offspring, while the supplementation of control and HFS-fed dams, respectively, induced higher hepatic Mme and Lepr mRNA levels after adult HFS intake compared with hfs-HFS offspring. In conclusion, maternal HFS diet during lactation influenced the response to an obesogenic diet in the adult progeny. Interestingly, dietary methyl donor supplementation in lactating mothers fed an obesogenic diet reduced liver fat accumulation, but increased adipose tissue storage in adult HFS-fed offspring.

Keywords

fatty liverlactationmaternal programmingmethyl donorsobesity
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 5 , Issue 5 , October 2014 , pp. 385 - 395
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Guh, DP, Zhang, W, Bansback, N, Amarsi, Z, Birmingham, CL, Anis, AH. The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis. BMC Public Health. 2009; 9, 88.CrossRefGoogle ScholarPubMed
2.Abete, I, Navas-Carretero, S, Marti, A, Martinez, JA. Nutrigenetics and nutrigenomics of caloric restriction. Prog Mol Biol Transl Sci. 2012; 108, 323–346.Google Scholar
3.Martinez, JA, Cordero, P, Campion, J, Milagro, FI. Interplay of early-life nutritional programming on obesity, inflammation and epigenetic outcomes. Proc Nutr Soc. 2012; 71, 276–283.CrossRefGoogle ScholarPubMed
4.Zou, M, Arentson, EJ, Teegarden, D, Koser, SL, Onyskow, L, Donkin, SS. Fructose consumption during pregnancy and lactation induces fatty liver and glucose intolerance in rats. Nutr Res. 2012; 32, 588–598.CrossRefGoogle ScholarPubMed
5.Blackmore, HL, Ozanne, SE. Maternal diet-induced obesity and offspring cardiovascular health. J Dev Orig Health Dis. 2013; 4, 338–347.Google Scholar
6.Roseboom, T, de Rooij, S, Painter, R. The Dutch famine and its long-term consequences for adult health. Early Hum Dev. 2006; 82, 485–491.CrossRefGoogle ScholarPubMed
7.Ohlsson, A, Shah, PS. Effects of the September 11, 2001 disaster on pregnancy outcomes: a systematic review. Acta Obstet Gynecol Scand. 2011; 90, 6–18.Google Scholar
8.Behl, M, Rao, D, Aagaard, K, et al. Evaluation of the association between maternal smoking, childhood obesity, and metabolic disorders: a national toxicology program workshop review. Environ Health Perspect. 2013; 121, 170–180.Google Scholar
9.Vucetic, Z, Kimmel, J, Totoki, K, Hollenbeck, E, Reyes, TM. Maternal high-fat diet alters methylation and gene expression of dopamine and opioid-related genes. Endocrinology. 2010; 151, 4756–4764.Google Scholar
10.Waterland, RA, Travisano, M, Tahiliani, KG, Rached, MT, Mirza, S. Methyl donor supplementation prevents transgenerational amplification of obesity. Int J Obes (Lond). 2008; 32, 1373–1379.Google Scholar
11.Lillycrop, KA, Phillips, ES, Jackson, AA, Hanson, MA, Burdge, GC. Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring. J Nutr. 2005; 135, 1382–1386.Google Scholar
12.Szeto, IM, Das, PJ, Aziz, A, Anderson, GH. Multivitamin supplementation of Wistar rats during pregnancy accelerates the development of obesity in offspring fed an obesogenic diet. Int J Obes (Lond). 2009; 33, 364–372.Google Scholar
13.Cordero, P, Campion, J, Milagro, FI, Martinez, JA. Dietary supplementation with methyl donor groups could prevent nonalcoholic fatty liver. Hepatology. 2011; 53, 2151–2152.CrossRefGoogle ScholarPubMed
14.Cordero, P, Gomez-Uriz, AM, Campion, J, Milagro, FI, Martinez, JA. Dietary supplementation with methyl donors reduces fatty liver and modifies the fatty acid synthase DNA methylation profile in rats fed an obesogenic diet. Genes Nutr. 2013; 8, 105–113.Google Scholar
15.Ding, Y, He, J, Liu, X, Chen, X, Long, C, Wang, Y. Expression of DNA methyltransferases in the mouse uterus during early pregnancy and susceptibility to dietary folate deficiency. Reproduction. 2012; 144, 91–100.CrossRefGoogle ScholarPubMed
16.Cordero, P, Campion, J, Milagro, FI, Martinez, JA. Transcriptomic and epigenetic changes in early liver steatosis associated to obesity: effect of dietary methyl donor supplementation. Mol Genet Metab. 2013; 110, 388–395.Google Scholar
17.Cordero, P, Gomez-Uriz, AM, Milagro, FI, Campion, J, Martinez, JA. Maternal weight gain induced by an obesogenic diet affects adipose accumulation, liver weight, and insulin homeostasis in the rat offspring depending on the sex. J Endocrinol Invest. 2012; 35, 981–986.Google Scholar
18.Faust, IM, Johnson, PR, Hirsch, J. Long-term effects of early nutritional experience on the development of obesity in the rat. J Nutr. 1980; 110, 2027–2034.Google Scholar
19.Nixon, JP, Zhang, M, Wang, C, et al.Evaluation of a quantitative magnetic resonance imaging system for whole body composition analysis in rodents. Obesity (Silver Spring). 2010; 18, 1652–1659.Google Scholar
20.Friedewald, WT, Levy, RI, Fredrickson, DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972; 18, 499–502.Google Scholar
21.Desjardins, P, Conklin, D. NanoDrop microvolume quantitation of nucleic acids. J Vis Exp. 2010; 45, e2562.Google Scholar
22.Livak, KJ, Schmittgen, TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001; 25, 402–408.Google Scholar
23.Paternain, L, de la Garza, AL, Batlle, MA, Milagro, FI, Martinez, JA, Campion, J. Prenatal stress increases the obesogenic effects of a high-fat-sucrose diet in adult rats in a sex-specific manner. Stress. 2013; 16, 220–232.Google Scholar
24.Kovacheva, VP, Mellott, TJ, Davison, JM, et al.Gestational choline deficiency causes global and Igf2 gene DNA hypermethylation by up-regulation of Dnmt1 expression. J Biol Chem. 2007; 282, 31777–31788.CrossRefGoogle ScholarPubMed
25.Hebbard, L, George, J. Animal models of nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol. 2011; 8, 35–44.CrossRefGoogle ScholarPubMed
26.Starlard-Davenport, A, Tryndyak, V, Kosyk, O, et al.Dietary methyl deficiency, microRNA expression and susceptibility to liver carcinogenesis. J Nutrigenet Nutrigenomics. 2010; 3, 259–266.Google Scholar
27.Khan, IY, Dekou, V, Douglas, G, et al. A high-fat diet during rat pregnancy or suckling induces cardiovascular dysfunction in adult offspring. Am J Physiol Regul Integr Comp Physiol. 2005; 288, 127–133.CrossRefGoogle ScholarPubMed
28.Flynn, ER, Alexander, BT, Lee, J, Hutchens, ZM Jr., Maric-Bilkan, C. High-fat/fructose feeding during prenatal and postnatal development in female rats increases susceptibility to renal and metabolic injury later in life. Am J Physiol Regul Integr Comp Physiol. 2013; 304, 278–285.CrossRefGoogle ScholarPubMed
29.Alzamendi, A, Castrogiovanni, D, Gaillard, RC, Spinedi, E, Giovambattista, A. Increased male offspring’s risk of metabolic-neuroendocrine dysfunction and overweight after fructose-rich diet intake by the lactating mother. Endocrinology. 2010; 151, 4214–4223.Google Scholar
30.Palou, M, Priego, T, Sanchez, J, Torrens, JM, Palou, A, Pico, C. Moderate caloric restriction in lactating rats protects offspring against obesity and insulin resistance in later life. Endocrinology. 2010; 151, 1030–1041.Google Scholar
31.United States Department of Agriculture (USDA). National nutrient database for standard reference. Retrieved 10 June 2014 from http://ndb.nal.usda.govGoogle Scholar
32.Perseghin, G. Lipids in the wrong place: visceral fat and nonalcoholic steatohepatitis. Diabetes Care. 2011; 34, S367–S370.Google Scholar
33.Fabbrini, E, Magkos, F, Mohammed, BS, et al. Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity. Proc Natl Acad Sci U S A. 2009; 106, 15430–15435.CrossRefGoogle Scholar
34.Pooya, S, Blaise, S, Moreno Garcia, M, et al. Methyl donor deficiency impairs fatty acid oxidation through PGC-1α hypomethylation and decreased ER-α, ERR-α, and HNF-4α in the rat liver. J Hepatol. 2012; 57, 344–351.Google Scholar
35.Huang, Y, He, Y, Sun, X, He, Y, Li, Y, Sun, C. Maternal high folic acid supplement promotes glucose intolerance and insulin resistance in male mouse offspring fed a high-fat diet. Int J Mol Sci. 2014; 15, 6298–6313.Google Scholar
36.Wells, JC. The thrifty phenotype as an adaptive maternal effect. Biol Rev Camb Philos Soc. 2007; 82, 143–172.CrossRefGoogle ScholarPubMed
37.Koo, SH. Nonalcoholic fatty liver disease: molecular mechanisms for the hepatic steatosis. Clin Mol Hepatol. 2013; 19, 210–215.Google Scholar
38.D’Alessandro, ME, Oliva, ME, Fortino, MA, Chicco, A. Maternal sucrose-rich diet and fetal programming: changes in hepatic lipogenic and oxidative enzymes and glucose homeostasis in adult offspring. Food Funct. 2014; 5, 446–453.Google Scholar
39.Speakman, J, Hambly, C, Mitchell, S, Król, E. Animal models of obesity. Obes Rev. 2007; 1, 55–61.Google Scholar
40.Ojeda, ML, Delgado-Villa, MJ, Llopis, R, Murillo, ML, Carreras, O. Lipid metabolism in ethanol-treated rat pups and adults: effects of folic acid. Alcohol Alcohol. 2008; 43, 544–550.Google Scholar
41.Aragno, M, Tomasinelli, CE, Vercellinatto, I, et al. SREBP-1c in nonalcoholic fatty liver disease induced by western-type high-fat diet plus fructose in rats. Free Radic Biol Med. 2009; 47, 1067–1074.Google Scholar
42.Strable, MS, Ntambi, JM. Genetic control of de novo lipogenesis: role in diet-induced obesity. Crit Rev Biochem Mol Biol. 2010; 45, 199–214.Google Scholar
43.Oliveira, LP, de Jesús, RP, Freire, TO, Oliveira, CP, Castro Lyra, A, Lyra, LG. Possible molecular mechanisms soy-mediated in preventing and treating nonalcoholic fatty liver disease. Nutr Hosp. 2012; 27, 991–998.Google Scholar
44.Majumder, S, Ghoshal, K, Datta, J, et al. Role of de novo DNA methyltransferases and methyl CpG-binding proteins in gene silencing in a rat hepatoma. J Biol Chem. 2002; 277, 16048–16058.Google Scholar
45.Jurkowska, RZ, Jurkowski, TP, Jeltsch, A. Structure and function of mammalian DNA methyltransferases. Chembiochem. 2011; 12, 206–222.Google Scholar
46.Gong, L, Pan, YX, Chen, H. Gestational low protein diet in the rat mediates Igf2 gene expression in male offspring via altered hepatic DNA methylation. Epigenetics. 2010; 5, 619–626.Google Scholar
47.Starley, BQ, Calcagno, CJ, Harrison, SA. Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection. Hepatology. 2010; 51, 1820–1832.Google Scholar
48.Kamei, Y, Suganami, T, Ehara, T, et al. Increased expression of DNA methyltransferase 3a in obese adipose tissue: studies with transgenic mice. Obesity (Silver Spring). 2010; 18, 314–321.Google Scholar
49.Lu, H, Cui, JY, Gunewardena, S, Yoo, B, Zhong, XB, Klaassen, CD. Hepatic ontogeny and tissue distribution of mRNAs of epigenetic modifiers in mice using RNA-sequencing. Epigenetics. 2012; 7, 914–929.CrossRefGoogle ScholarPubMed
50.Cordero, P, Milagro, FI, Campion, J, Martinez, JA. Maternal methyl donors supplementation during lactation prevents the hyperhomocysteinemia induced by a high-fat-sucrose intake by dams. Int J Mol Sci. 2013; 14, 24422–24437.Google Scholar
51.Panchal, SK, Brown, L. Rodent models for metabolic syndrome research. J Biomed Biotechnol. 2011; 2011, 351982.CrossRefGoogle ScholarPubMed
52.Garcia, AP, Palou, M, Priego, T, Sanchez, J, Palou, A, Pico, C. Moderate caloric restriction during gestation results in lower arcuate nucleus NPY- and alphaMSH-neurons and impairs hypothalamic response to fed/fasting conditions in weaned rats. Diabetes Obes Metab. 2010; 12, 403–413.Google Scholar
53.Gomez-Ruiz, A, Milagro, FI, Campion, J, Martinez, JA, de Miguel, C. High-fat diet feeding alters metabolic response to fasting/non fasting conditions. Effect on caveolin expression and insulin signalling. Lipids Health Dis.. 2011; 10, 55.Google Scholar
54.Tsuchiya, H, Ikeda, Y, Ebata, Y, et al. Retinoids ameliorate insulin resistance in a leptin-dependent manner in mice. Hepatology. 2012; 56, 1319–1330.CrossRefGoogle Scholar
55.Tsiambas, E, Georgiannos, SN, Salemis, N, et al. Significance of estrogen receptor 1 (ESR-1) gene imbalances in colon and hepatocellular carcinomas based on tissue microarrays analysis. Med Oncol. 2011; 28, 934–940.Google Scholar
56.Byrne, JA, Meara, NJ, Rayner, AC, Thompson, RJ, Knisely, AS. Lack of hepatocellular CD10 along bile canaliculi is physiologic in early childhood and persistent in Alagille syndrome. Lab Invest. 2007; 87, 1138–1148.CrossRefGoogle ScholarPubMed