Nutrition Research and Practice

The Korean Nutrition Society (한국영양학회)
권호 표지
DOI QR코드

DOI QR Code

Effects of disturbed liver growth and oxidative stress of high-fat diet-fed dams on cholesterol metabolism in offspring mice

  • Kim, Juyoung (Department of Food and Nutrition, Seoul National University) ;
  • Kim, Juhae (Department of Food and Nutrition, Seoul National University) ;
  • Kwon, Young Hye (Department of Food and Nutrition, Seoul National University)
  • Received : 2015.12.31
  • Accepted : 2016.04.11
  • Published : 2016.08.01
Download PDF
⟨ Previous Next ⟩

Abstract

BACKGROUND/OBJECTIVES: Changes in nutritional status during gestation and lactation have detrimental effects on offspring metabolism. Several animal studies have shown that maternal high-fat diet (HFD) can predispose the offspring to development of obesity and metabolic diseases, however the mechanisms underlying these transgenerational effects are poorly understood. Therefore, we examined the effect of maternal HFD consumption on metabolic phenotype and hepatic expression of involved genes in dams to determine whether any of these parameters were associated with the metabolic outcomes in the offspring. MATERIALS/METHODS: Female C57BL/6 mice were fed a low-fat diet (LFD: 10% calories from fat) or a high-fat diet (HFD: 45% calories from fat) for three weeks before mating, and during pregnancy and lactation. Dams and their male offspring were studied at weaning. RESULTS: Dams fed an HFD had significantly higher body and adipose tissue weights and higher serum triglyceride and cholesterol levels than dams fed an LFD. Hepatic lipid levels and mRNA levels of genes involved in lipid metabolism, including $LXR{\alpha}$, SREBP-2, FXR, LDLR, and ABCG8 were significantly changed by maternal HFD intake. Significantly lower total liver DNA and protein contents were observed in dams fed an HFD, implicating the disturbed liver adaptation in the pregnancy-related metabolic demand. HFD feeding also induced significant oxidative stress in serum and liver of dams. Offspring of dams fed an HFD had significantly higher serum cholesterol levels, which were negatively correlated with liver weights of dams and positively correlated with hepatic lipid peroxide levels in dams. CONCLUSIONS: Maternal HFD consumption induced metabolic dysfunction, including altered liver growth and oxidative stress in dams, which may contribute to the disturbed cholesterol homeostasis in the early life of male mice offspring.

Keywords

References

  1. Burdge GC, Lillycrop KA. Nutrition, epigenetics, and developmental plasticity: implications for understanding human disease. Annu Rev Nutr 2010;30:315-39. https://doi.org/10.1146/annurev.nutr.012809.104751
  2. Rinaudo P, Wang E. Fetal programming and metabolic syndrome. Annu Rev Physiol 2012;74:107-30. https://doi.org/10.1146/annurev-physiol-020911-153245
  3. 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;1842:507-19. https://doi.org/10.1016/j.bbadis.2013.07.006
  4. Cannon MV, Buchner DA, Hester J, Miller H, Sehayek E, Nadeau JH, Serre D. Maternal nutrition induces pervasive gene expression changes but no detectable DNA methylation differences in the liver of adult offspring. PLoS One 2014;9:e90335. https://doi.org/10.1371/journal.pone.0090335
  5. Cianfarani S, Agostoni C, Bedogni G, Berni Canani R, Brambilla P, Nobili V, Pietrobelli A. Effect of intrauterine growth retardation on liver and long-term metabolic risk. Int J Obes (Lond) 2012;36:1270-7. https://doi.org/10.1038/ijo.2012.54
  6. 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:R711-22. https://doi.org/10.1152/ajpregu.00310.2010
  7. Bringhenti I, Ornellas F, Martins MA, Mandarim-de-Lacerda CA, Aguila MB. Early hepatic insult in the offspring of obese maternal mice. Nutr Res 2015;35:136-45. https://doi.org/10.1016/j.nutres.2014.11.006
  8. Yang KF, Cai W, Xu JL, Shi W. Maternal high-fat diet programs Wnt genes through histone modification in the liver of neonatal rats. J Mol Endocrinol 2012;49:107-14.
  9. 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;15:14967-83. https://doi.org/10.3390/ijms150914967
  10. Zou Y, Hu M, Bao Q, Chan JY, Dai G. Nrf2 participates in regulating maternal hepatic adaptations to pregnancy. J Cell Sci 2013;126:1618-25. https://doi.org/10.1242/jcs.118109
  11. Herrera E. Metabolic adaptations in pregnancy and their implications for the availability of substrates to the fetus. Eur J Clin Nutr 2000;54 Suppl 1:S47-51. https://doi.org/10.1038/sj.ejcn.1600984
  12. Bustamante JJ, Copple BL, Soares MJ, Dai G. Gene profiling of maternal hepatic adaptations to pregnancy. Liver Int 2010;30:406-15. https://doi.org/10.1111/j.1478-3231.2009.02183.x
  13. Papacleovoulou G, Abu-Hayyeh S, Williamson C. Nuclear receptordriven alterations in bile acid and lipid metabolic pathways during gestation. Biochim Biophys Acta 2011;1812:879-87. https://doi.org/10.1016/j.bbadis.2010.11.001
  14. Athippozhy A, Huang L, Wooton-Kee CR, Zhao T, Jungsuwadee P, Stromberg AJ, Vore M. Differential gene expression in liver and small intestine from lactating rats compared to age-matched virgin controls detects increased mRNA of cholesterol biosynthetic genes. BMC Genomics 2011;12:95. https://doi.org/10.1186/1471-2164-12-95
  15. Niculescu MD, Lupu DS. High fat diet-induced maternal obesity alters fetal hippocampal development. Int J Dev Neurosci 2009;27:627-33. https://doi.org/10.1016/j.ijdevneu.2009.08.005
  16. Shaw MA, Rasmussen KM, Myers TR. Consumption of a high fat diet impairs reproductive performance in Sprague-Dawley rats. J Nutr 1997;127:64-9. https://doi.org/10.1093/jn/127.1.64
  17. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351-8. https://doi.org/10.1016/0003-2697(79)90738-3
  18. Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 1957;226:497-509.
  19. Jeon S, Park YJ, Kwon YH. Genistein alleviates the development of nonalcoholic steatohepatitis in ApoE(-/-) mice fed a high-fat diet. Mol Nutr Food Res 2014;58:830-41. https://doi.org/10.1002/mnfr.201300112
  20. Flowers JB, Rabaglia ME, Schueler KL, Flowers MT, Lan H, Keller MP, Ntambi JM, Attie AD. Loss of stearoyl-CoA desaturase-1 improves insulin sensitivity in lean mice but worsens diabetes in leptin-deficient obese mice. Diabetes 2007;56:1228-39. https://doi.org/10.2337/db06-1142
  21. Matsui H, Yokoyama T, Sekiguchi K, Iijima D, Sunaga H, Maniwa M, Ueno M, Iso T, Arai M, Kurabayashi M. Stearoyl-CoA desaturase-1 (SCD1) augments saturated fatty acid-induced lipid accumulation and inhibits apoptosis in cardiac myocytes. PLoS One 2012;7:e33283. https://doi.org/10.1371/journal.pone.0033283
  22. Dudley KJ, Sloboda DM, Connor KL, Beltrand J, Vickers MH. Offspring of mothers fed a high fat diet display hepatic cell cycle inhibition and associated changes in gene expression and DNA methylation. PLoS One 2011;6:e21662. https://doi.org/10.1371/journal.pone.0021662
  23. Mischke M, Pruis MG, Boekschoten MV, Groen AK, Fitri AR, van de Heijning BJ, Verkade HJ, Muller M, Plosch T, Steegenga WT. Maternal Western-style high fat diet induces sex-specific physiological and molecular changes in two-week-old mouse offspring. PLoS One 2013;8:e78623. https://doi.org/10.1371/journal.pone.0078623
  24. Al-Gubory KH, Fowler PA, Garrel C. The roles of cellular reactive oxygen species, oxidative stress and antioxidants in pregnancy outcomes. Int J Biochem Cell Biol 2010;42:1634-50. https://doi.org/10.1016/j.biocel.2010.06.001
  25. Sen S, Simmons RA. Maternal antioxidant supplementation prevents adiposity in the offspring of Western diet-fed rats. Diabetes 2010;59:3058-65. https://doi.org/10.2337/db10-0301
  26. Baardman ME, Kerstjens-Frederikse WS, Berger RM, Bakker MK, Hofstra RM, Plosch T. The role of maternal-fetal cholesterol transport in early fetal life: current insights. Biol Reprod 2013;88:24.
  27. Ashino NG, Saito KN, Souza FD, Nakutz FS, Roman EA, Velloso LA, Torsoni AS, Torsoni MA. Maternal high-fat feeding through pregnancy and lactation predisposes mouse offspring to molecular insulin resistance and fatty liver. J Nutr Biochem 2012;23:341-8. https://doi.org/10.1016/j.jnutbio.2010.12.011
  28. Hernandez LL, Grayson BE, Yadav E, Seeley RJ, Horseman ND. High fat diet alters lactation outcomes: possible involvement of inflammatory and serotonergic pathways. PLoS One 2012;7:e32598. https://doi.org/10.1371/journal.pone.0032598
  29. Apte U, Zeng G, Thompson MD, Muller P, Micsenyi A, Cieply B, Kaestner KH, Monga SP. beta-Catenin is critical for early postnatal liver growth. Am J Physiol Gastrointest Liver Physiol 2007;292:G1578-85. https://doi.org/10.1152/ajpgi.00359.2006
  30. Ito J, Nakagawa K, Kato S, Miyazawa T, Kimura F, Miyazawa T. The combination of maternal and offspring high-fat diets causes marked oxidative stress and development of metabolic syndrome in mouse offspring. Life Sci 2016;151:70-5. https://doi.org/10.1016/j.lfs.2016.02.089

Cited by

  1. Erratum: Effects of disturbed liver growth and oxidative stress of high-fat diet-fed dams on cholesterol metabolism in offspring mice vol.11, pp.5, 2017, https://doi.org/10.4162/nrp.2017.11.5.435
  2. Combined oral supplementation of chromium picolinate, docosahexaenoic acid, and boron enhances neuroprotection in rats fed a high-fat diet vol.47, pp.13036165, 2017, https://doi.org/10.3906/sag-1701-54
  3. Gender-divergent expression of lipid and bile acid metabolism-related genes in adult mice offspring of dams fed a high-fat diet vol.43, pp.2, 2018, https://doi.org/10.1007/s12038-018-9750-9
  4. Placental mitochondrial biogenesis and function was slightly changed by gestational hypercholesterolemia in full-term pregnant women vol.9, pp.4, 2018, https://doi.org/10.1017/S2040174418000077
  5. Oxidative Stress Profile of Mothers and Their Offspring after Maternal Consumption of High-Fat Diet in Rodents: A Systematic Review and Meta-Analysis vol.2021, pp.None, 2016, https://doi.org/10.1155/2021/9073859