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Transgenerational epigenetic inheritance of diabetes risk as a consequence of early nutritional imbalances

  • Josep C. Jimenez-Chillaron (a1), Marta Ramon-Krauel (a1), Silvia Ribo (a1) and Ruben Diaz (a1)

Abstract

In today's world, there is an unprecedented rise in the prevalence of chronic metabolic diseases, including obesity, insulin resistance and type 2 diabetes (T2D). The pathogenesis of T2D includes both genetic and environmental factors, such as excessive energy intake and physical inactivity. It has recently been suggested that environmental factors experienced during early stages of development, including the intrauterine and neonatal periods, might play a major role in predisposing individuals to T2D. Furthermore, several studies have shown that such early environmental conditions might even contribute to disease risk in further generations. In this review, we summarise recent data describing how parental nutrition during development increases the risk of diabetes in the offspring. We also discuss the potential mechanisms underlying transgenerational inheritance of metabolic disease, with particular emphasis on epigenetic mechanisms.

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Corresponding author

* Corresponding author: J. C. Jiménez-Chillarón, fax +34-936009771, email jjimenezc@fsjd.org

References

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1. World Health Organization (2005) Fact sheet no. 312. http://www.who.int/mediacentre/factsheets/fs312/en (accessed June 2015).
2. Finucane, MM, Stevens, GA, Cowan, MJ et al. (2011) National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9·1 million participants. Lancet 377, 557567.
3. Danaei, G, Finucane, MM, Lu, Y et al. (2011) National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants. Lancet 378, 3140.
4. Wild, S, Roglic, G, Green, A et al. (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27, 10471053.
5. Morrish, NJ, Wang, SL, Stevens, LK et al. (2001) Mortality and causes of death in the WHO multinational study of vascular disease in diabetes. Diabetologia 44, Suppl 2, S14S21.
6. Bianchini, F, Kaaks, R & Vainio, H (2002) Overweight, obesity, and cancer risk. Lancet Oncol 3, 565574.
7. Grarup, N, Sandholt, CH, Hansen, T et al. (2014) Genetic susceptibility to type 2 diabetes and obesity: from genome-wide association studies to rare variants and beyond. Diabetologia 57, 15281541.
8. Schwenk, RW, Vogel, H & Schürmann, A (2013) Genetic and epigenetic control of metabolic health. Mol Metab 2, 337347.
9. Yanovski, SZ & Yanovski, JA (2002) Obesity. N Engl J Med 346, 591602.
10. Kahn, BB & Flier, JS (2000) Obesity and insulin resistance. J Clin Invest 106, 473481.
11. Gluckman, PD, Hanson, MA, Cooper, C et al. (2008) Effect of in utero and early-life conditions on adult health and disease. N Engl J Med 359, 6173.
12. Schulz, LC (2010) The Dutch Hunger Winter and the developmental origins of health and disease. Proc Natl Acad Sci U S A 107, 1675716758.
13. Lumey, LH, Stein, AD, Kahn, HS et al. (2009) Lipid profiles in middle-aged men and women after famine exposure during gestation: the Dutch Hunger Winter families study. Am J Clin Nutr 89, 17371743.
14. de Rooij, SR, Painter, RC, Phillips, DI et al. (2006) Impaired insulin secretion after prenatal exposure to the Dutch famine. Diabetes Care 29, 18971901.
15. Roseboom, TJ, van der Meulen, JH, Ravelli, AC et al. (1999) Blood pressure in adults after prenatal exposure to famine. J Hypertens 17, 325330.
16. Ravelli, AC, van Der Meulen, JH, Osmond, C et al. (1999) Obesity at the age of 50 y in men and women exposed to famine prenatally. Am J Clin Nutr 70, 811816.
17. Duque-Guimarães, DE & Ozanne, SE (2013) Nutritional programming of insulin resistance: causes and consequences. Trends Endocrinol Metab 24, 525535.
18. Saenger, P, Czernichow, P, Hughes, I et al. (2007) Small for gestational age: short stature and beyond. Endocr Rev. 28, 219251.
19. McMillen, IC & Robinson, JS (2005) Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. Physiol Rev 85, 571633.
20. Hochberg, Z, Feil, R, Constancia, M et al. (2011) Child health, developmental plasticity, and epigenetic programming. Endocr Rev 32, 159224.
21. Jimenez-Chillaron, JC, Diaz, R, Ramon-Krauel, M et al. (2014) Transgenerational epigenetic inheritance of type 2 diabetes. In Transgenerational Epigenetics. Evidence and Debate, 1st ed., pp. 281301 [Tollefsbol, T, editor]. London, Oxford, Boston, New York, San Diego: Academic Press (Elsevier).
22. Roseboom, TJ & Watson, ED (2012) The next generation of disease risk: are the effects of prenatal nutrition transmitted across generations? Evidence from animal and human studies. Placenta 33, Suppl. 2, e40e44.
23. Veenendaal, MV, Painter, RC, de Rooij, SR et al. (2013) Transgenerational effects of prenatal exposure to the 1944–45 Dutch famine. BJOG 120, 548553.
24. Kaati, G, Bygren, LO, Pembrey, M et al. (2007) Transgenerational response to nutrition, early life circumstances and longevity. Eur J Hum Genet 15, 784790.
25. Kaati, G, Bygren, LO & Edvinsson, S (2002) Cardiovascular and diabetes mortality determined by nutrition during parents’ and grandparents’ slow growth period. Eur J Hum Genet 10, 682688.
26. Bygren, LO, Kaati, G & Edvinsson, S (2001) Longevity determined by paternal ancestors’ nutrition during their slow growth period. Acta Biotheor 49, 5359.
27. Pembrey, M, Saffery, R, Bygren, LO et al. (2014) Human transgenerational responses to early-life experience: potential impact on development, health and biomedical research. J Med Genet 51, 563572.
28. Gluckman, PD, Hanson, MA & Beedle, AS (2007) Non-genomic transgenerational inheritance of disease risk. Bioessays 29, 145154.
29. Bonduriansky, R (2012) Rethinking heredity, again. Trends Ecol Evol 27, 330336.
30. Susiarjo, M & Bartolomei, MS (2014) Epigenetics. You are what you eat, but what about your DNA? Science 345, 733734.
31. Einstein, FH (2014) Multigenerational effects of maternal undernutrition. Cell Metab 19, 893894.
32. Uller, T. (2014) Evolutionary perspectives on transgenerational epigenetics. In Transgenerational Epigenetics. Evidence and Debate, 1st ed., pp. 175185 [Tollefsbol, T, editor]. London, Oxford, Boston, New York, San Diego: Academic Press (Elsevier).
33. Jablonka, E & Lamb, MJ (editors) (2005) Evolution in Four Dimensions. Genetic, Epigenetic, Behavioral and Symbolic Variation in the History of Life. Boston: MIT Press.
34. Aerts, L & Van Assche, FA (2006) Animal evidence for the transgenerational development of diabetes mellitus. Int J Biochem Cell Biol 38, 894903.
35. Blondeau, B, Avril, I, Duchene, B et al. (2002) Endocrine pancreas development is altered in foetuses from rats previously showing intra-uterine growth retardation in response to malnutrition. Diabetologia 45, 394401.
36. Zambrano, E, Bautista, CJ, Deás, M et al. (2006) 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 571, 221230.
37. Benyshek, DC, Johnston, CS & Martin, JF (2006) Glucose metabolism is altered in the adequately-nourished grand-offspring (F3 generation) of rats malnourished during gestation and perinatal life. Diabetologia 49, 11171119.
38. Burdge, GC, Hoile, SP, Uller, T et al. (2011) Progressive, transgenerational changes in offspring phenotype and epigenotype following nutritional transition. PLoS ONE 6, e28282.
39. King, V, Dakin, RS, Liu, L et al. (2013) Maternal obesity has little effect on the immediate offspring but impacts on the next generation. Endocrinology 154, 25142524.
40. Ferguson-Smith, AC & Patti, ME (2011) You are what your dad ate. Cell Metab 13, 115117.
41. Rando, OJ (2012) Daddy issues: paternal effects on phenotype. Cell 151, 702708.
42. Rando, OJ & Simmons, RA (2015) I'm eating for two: parental dietary effects on offspring metabolism. Cell 161, 93105.
43. Skinner, MK (2008) What is an epigenetic transgenerational phenotype? F3 or F2. Reprod Toxicol 25, 26.
44. Jirtle, RL & Skinner, MK (2007) Environmental epigenomics and disease susceptibility. Nat Rev Genet 8, 253262.
45. McKay, JA & Mathers, JC (2011) Diet induced epigenetic changes and their implications for health. Acta Physiol 202, 103118.
46. Wang, J, Wu, Z, Li, D et al. (2012) Nutrition, epigenetics, and metabolic syndrome. Antioxid Redox Signal 17, 282301.
47. Jiménez-Chillarón, JC, Díaz, R, Martínez, D et al. (2012) The role of nutrition on epigenetic modifications and their implications on health. Biochimie 94, 22422263.
48. Loenen, WA (2006) S-adenosylmethionine: jack of all trades and master of everything? Biochem Soc Trans 34, 330333.
49. Feil, R & Fraga, MF (2011) Epigenetics and the environment: emerging patterns and implications. Nat Rev Genet 13, 97109.
50. Pogribny, IP, Tryndyak, VP, Bagnyukova, TV et al. (2009) Hepatic epigenetic phenotype predetermines individual susceptibility to hepatic steatosis in mice fed a lipogenic methyl-deficient diet. J Hepatol 51, 176186.
51. Pogribny, IP, Karpf, AR, James, SR et al. (2008) Epigenetic alterations in the brains of Fisher 344 rats induced by long-term administration of folate/methyl-deficient diet. Brain Res 1237, 2534.
52. Deminice, R, Portari, GV, Marchini, JS et al. (2009) Effects of a low-protein diet on plasma amino acid and homocysteine levels and oxidative status in rats. Ann Nutr Metab 54, 202207.
53. Pham, TX & Lee, J (2012) Dietary regulation of histone acetylases and deacetylases for the prevention of metabolic diseases. Nutrients 4, 18681886.
54. Kaelin, WG & McKnight, SL (2013) Influence of metabolism on epigenetics and disease. Cell 153, 5669.
55. Radford, EJ, Ito, M, Shi, H et al. (2014) In utero effects. In utero undernourishment perturbs the adult sperm methylome and intergenerational metabolism. Science 345, 1255903.
56. Martínez, D, Pentinat, T & Ribó, S et al. (2014) In utero undernutrition in male mice programs liver lipid metabolism in the second-generation offspring involving altered Lxra DNA methylation. Cell Metab 19, 941951.
57. Carone, BR, Fauquier, L, Habib, N et al. (2010) Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals. Cell 143, 10841096.
58. Wei, Y, Yang, CR, Wei, YP et al. (2014) Paternally induced transgenerational inheritance of susceptibility to diabetes in mammals. Proc Natl Acad Sci U S A 111, 18731878.
59. Jablonka, E & Raz, G (2009) Transgenerational epigenetic inheritance: prevalence, mechanisms, and implications for the study of heredity and evolution. Q Rev Biol 84, 131176.
60. Grossniklaus, U, Kelly, WG, Kelly, B et al. (2013) Transgenerational epigenetic inheritance: how important is it? Nat Rev Genet 14, 228235.
61. Heard, E & Martienssen, RA (2014) Transgenerational epigenetic inheritance: myths and mechanisms. Cell 157, 95109.
62. Peaston, AE & Whitelaw, E (2006) Epigenetics and phenotypic variation in mammals. Mamm Genome 17, 365374.
63. Seisenberger, S, Peat, JR, Hore, TA et al. (2013) Reprogramming DNA methylation in the mammalian life cycle: building and breaking epigenetic barriers. Philos Trans R Soc Lond B Biol Sci 368, 20110330.
64. DeChiara, TM, Robertson, EJ & Efstratiadis, A (1991) Parental imprinting of the mouse insulin-like growth factor II gene. Cell 64, 849859.
65. Bartolomei, MS, Webber, AL, Brunkow, ME et al. (1993) Epigenetic mechanisms underlying the imprinting of the mouse H19 gene. Genes Dev 7, 16631673.
66. Allis, CD, Jenuwein, T & Reinberg, D (editors) (2007) Epigenetics. New York: Cold Spring Harbor Laboratory Press.
67. Daxinger, L & Whitelaw, E (2012) Understanding transgenerational epigenetic inheritance via the gametes in mammals. Nat Rev Genet 13, 153162.
68. Lane, N, Dean, W, Erhardt, S et al. (2003) Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse. Genesis 35, 8893.
69. Hajkova, P, Ancelin, K, Waldmann, T et al. (2008) Chromatin dynamics during epigenetic reprogramming in the mouse germ line. Nature 452, 877881.
70. Popp, C, Dean, W, Feng, S et al. (2010) Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency. Nature 463, 11011105.
71. Borgel, J, Guibert, S, Li, Y et al. (2010) Targets and dynamics of promoter DNA methylation during early mouse development. Nat Genet 42, 10931100.
72. Hackett, JA, Sengupta, R, Zylicz, JJ et al. (2013) Germline DNA demethylation dynamics and imprint erasure through 5-hydroxymethylcytosine. Science 339, 448452.
73. Hackett, JA & Surani, MA (2013) Beyond DNA: programming and inheritance of parental methylomes. Cell 153, 737739.
74. Seisenberger, S, Andrews, S, Krueger, F et al. (2012) The dynamics of genome-wide DNA methylation reprogramming in mouse primordial germ cells. Mol Cell 48, 849862.
75. Hammoud, SS, Nix, DA, Zhang, H et al. (2009) Distinctive chromatin in human sperm packages genes for embryo development. Nature 460, 473478.
76. Brykczynska, U, Hisano, M, Erkek, S et al. (2010) Repressive and active histone methylation mark distinct promoters in human and mouse spermatozoa. Nat Struct Mol Biol 17, 679687.
77. Krawetz, SA (2005) Paternal contribution: new insights and future challenges. Nat Rev Genet 6, 633642.
78. Casas, E & Vavouri, T (2014) Sperm epigenomics: challenges and opportunities. Front Genet 5, 330.
79. Rassoulzadegan, M, Grandjean, V, Gounon, P et al. (2007) Inheritance of an epigenetic change in the mouse: a new role for RNA. Biochem Soc Trans 35, 623625.
80. Rassoulzadegan, M, Grandjean, V, Gounon, P et al. (2006) RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse. Nature 441, 469474.
81. Gan, H, Lin, X, Zhang, Z et al. (2011) piRNA profiling during specific stages of mouse spermatogenesis. RNA 17, 11911203.
82. Watanabe, T, Tomizawa, S, Mitsuya, K et al. (2011) Role for piRNAs and noncoding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus. Science 332, 848852.
83. Kuramochi-Miyagawa, S, Watanabe, T, Gotoh, K et al. (2008) DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes. Genes Dev 22, 908917.
84. Fullston, T, Ohlsson Teague, EM et al. (2013) Paternal obesity initiates metabolic disturbances in two generations of mice with incomplete penetrance to the F2 generation and alters the transcriptional profile of testis and sperm microRNA content. FASEB J 27, 42264243.
85. Ng, SF, Lin, RC, Laybutt, DR et al. (2010) Chronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring. Nature 467, 963966.
86. Jimenez-Chillaron, JC, Hernandez-Valencia, M, Reamer, C et al. (2005) Beta-cell secretory dysfunction in the pathogenesis of low birth weight-associated diabetes: a murine model. Diabetes 54, 702711.
87. Jimenez-Chillaron, JC, Hernandez-Valencia, M, Lightner, A et al. (2006) Reductions in caloric intake and early postnatal growth prevent glucose intolerance and obesity associated with low birth weight. Diabetologia 49, 19741984.
88. Jimenez-Chillaron, JC, Isganaitis, E, Charalambous, M et al. (2009) Intergenerational transmission of glucose intolerance and obesity by in utero undernutrition in mice. Diabetes 58, 460468.
89. Blewitt, ME, Vickaryous, NK, Paldi, A et al. (2006) Dynamic reprogramming of DNA methylation at an epigenetically sensitive allele in mice. PLoS Genet 2, e49.
90. Dunn, GA & Bale, TL (2009) Maternal high-fat diet promotes body length increases and insulin insensitivity in second-generation mice. Endocrinology 150, 49995009.
91. Dunn, GA & Bale, TL (2011) Maternal high-fat diet effects on third-generation female body size via the paternal lineage. Endocrinology 152, 22282236.
92. Ding, GL, Wang, FF, Shu, J et al. (2012) Transgenerational glucose intolerance with Igf2/H19 epigenetic alterations in mouse islet induced by intrauterine hyperglycemia. Diabetes 61, 11331142.

Keywords

Transgenerational epigenetic inheritance of diabetes risk as a consequence of early nutritional imbalances

  • Josep C. Jimenez-Chillaron (a1), Marta Ramon-Krauel (a1), Silvia Ribo (a1) and Ruben Diaz (a1)

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