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The Effect of Maternal Overnutrition on Reward and Anxiety in Offspring

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Parental Obesity: Intergenerational Programming and Consequences

Part of the book series: Physiology in Health and Disease ((PIHD))

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Abstract

Obesity has reached epidemic levels in developed countries. Maternal overnutrition has been linked to a number of poor health outcomes in offspring, including metabolic, cardiovascular and mental disorders, some of which do not become apparent until later in life. In particular, maternal overnutrition is linked to increased risk for hedonic and stress dysfunctions. Previous studies in animal models indicate that maternal overnutrition, typically using a diet high in fat, impacts the function of the mesolimbic pathway, leading to attenuated function of the reward system and decreased dopamine-related behaviour. Also maternal overnutrition affects the function of the hypothalamic–pituitary–adrenal axis, leading to activated stress system and increased anxiety-like behaviour. This chapter focuses on what is known about the effects of maternal intake of high-fat diet on the reward and stress systems in offspring brain and behaviour. We discuss the likely role of epigenetic regulation of these pathways in the long-term changes in brain function associated with the perinatal environment.

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Abbreviations

D1R:

Dopamine receptor D1

D2R:

Dopamine receptor D2

DAT:

Dopamine transporter

GR:

Glucocorticoid receptor

HPA:

Hypothalamic–pituitary–adrenal

MR:

Mineralocorticoid receptor

NAC:

Nucleus accumbens

PFC:

Prefrontal cortex

TH:

Tyrosine hydroxylase

VTA:

Ventral tegmental area

References

  1. Ogden CL, Carroll MD, Kit BK, Flegal KM (2012) Prevalence of obesity and trends in body mass index among US children and adolescents, 1999-2010. JAMA 307(5):483–490

    Article  PubMed  Google Scholar 

  2. Freedman DS, Kahn HS, Mei Z, Grummer-Strawn LM, Dietz WH, Srinivasan SR et al (2007) Relation of body mass index and waist-to-height ratio to cardiovascular disease risk factors in children and adolescents: the Bogalusa Heart Study. Am J Clin Nutr 86(1):33–40

    CAS  PubMed  Google Scholar 

  3. Rivera HM, Christiansen KJ, Sullivan EL (2015) The role of maternal obesity in the risk of neuropsychiatric disorders. Front Neurosci 9:194, Pubmed Central PMCID: 4471351

    Article  PubMed  PubMed Central  Google Scholar 

  4. Leddy MA, Power ML, Schulkin J (2008) The impact of maternal obesity on maternal and fetal health. Rev Obstet Gynecol 1(4):170–178, Pubmed Central PMCID: 2621047

    PubMed  PubMed Central  Google Scholar 

  5. Howie GJ, Sloboda DM, Kamal T, Vickers MH (2009) Maternal nutritional history predicts obesity in adult offspring independent of postnatal diet. J Physiol 587(Pt 4):905–915, Pubmed Central PMCID: 2669979

    Article  CAS  PubMed  Google Scholar 

  6. Dabelea D, Crume T (2011) Maternal environment and the transgenerational cycle of obesity and diabetes. Diabetes 60(7):1849–1855, Pubmed Central PMCID: 3121421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Tobler PN, Fiorillo CD, Schultz W (2005) Adaptive coding of reward value by dopamine neurons. Science 307(5715):1642–1645

    Article  CAS  PubMed  Google Scholar 

  8. Kelley AE, Berridge KC (2002) The neuroscience of natural rewards: relevance to addictive drugs. J Neurosci 22(9):3306–3311

    CAS  PubMed  Google Scholar 

  9. Vucetic Z, Kimmel J, Totoki K, Hollenbeck E, Reyes TM (2010) Maternal high-fat diet alters methylation and gene expression of dopamine and opioid-related genes. Endocrinology 151(10):4756–4764, Pubmed Central PMCID: 2946145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ong ZY, Muhlhausler BS (2011) Maternal “junk-food” feeding of rat dams alters food choices and development of the mesolimbic reward pathway in the offspring. FASEB J 25(7):2167–2179, Pubmed Central PMCID: 3114523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Naef L, Srivastava L, Gratton A, Hendrickson H, Owens SM, Walker CD (2008) Maternal high fat diet during the perinatal period alters mesocorticolimbic dopamine in the adult rat offspring: reduction in the behavioral responses to repeated amphetamine administration. Psychopharmacology (Berl) 197(1):83–94

    Article  CAS  Google Scholar 

  12. Sasaki A, de Vega WC, St-Cyr S, Pan P, McGowan PO (2013) Perinatal high fat diet alters glucocorticoid signaling and anxiety behavior in adulthood. Neuroscience 240:1–12

    Article  CAS  PubMed  Google Scholar 

  13. Sasaki A, de Vega W, Sivanathan S, St-Cyr S, McGowan PO (2014) Maternal high-fat diet alters anxiety behavior and glucocorticoid signaling in adolescent offspring. Neuroscience 272:92–101

    Article  CAS  PubMed  Google Scholar 

  14. Koob GF (2008) A role for brain stress systems in addiction. Neuron 59(1):11–34, Pubmed Central PMCID: 2748830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Volkow ND, Wang GJ, Tomasi D, Baler RD (2013) The addictive dimensionality of obesity. Biol Psychiatry 73(9):811–818

    Article  PubMed  PubMed Central  Google Scholar 

  16. Ramamoorthy TG, Begum G, Harno E, White A (2015) Developmental programming of hypothalamic neuronal circuits: impact on energy balance control. Front Neurosci 9:126

    Google Scholar 

  17. Taylor PD, Poston L (2007) Developmental programming of obesity in mammals. Exp Physiol 92(2):287–298

    Article  CAS  PubMed  Google Scholar 

  18. Narayanan NS, Guarnieri DJ, DiLeone RJ (2010) Metabolic hormones, dopamine circuits, and feeding. Front Neuroendocrinol 31(1):104–112, Pubmed Central PMCID: 2813908

    Article  CAS  PubMed  Google Scholar 

  19. Van den Heuvel DM, Pasterkamp RJ (2008) Getting connected in the dopamine system. Prog Neurobiol 85(1):75–93

    Article  PubMed  Google Scholar 

  20. Okubo H, Crozier SR, Harvey NC, Godfrey KM, Inskip HM, Cooper C et al (2014) Maternal dietary glycemic index and glycemic load in early pregnancy are associated with offspring adiposity in childhood: the Southampton Women’s Survey. Am J Clin Nutr 100(2):676–683

    Article  CAS  PubMed  Google Scholar 

  21. Brion MJ, Ness AR, Rogers I, Emmett P, Cribb V, Davey Smith G et al (2010) Maternal macronutrient and energy intakes in pregnancy and offspring intake at 10 y: exploring parental comparisons and prenatal effects. Am J Clin Nutr 91(3):748–756, Pubmed Central PMCID: 2822901

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Meier U, Gressner AM (2004) Endocrine regulation of energy metabolism: review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin, and resistin. Clin Chem 50(9):1511–1525

    Article  CAS  PubMed  Google Scholar 

  23. Chang GQ, Gaysinskaya V, Karatayev O, Leibowitz SF (2008) Maternal high-fat diet and fetal programming: increased proliferation of hypothalamic peptide-producing neurons that increase risk for overeating and obesity. J Neurosci 28(46):12107–12119, Pubmed Central PMCID: 2752048

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Bayol SA, Farrington SJ, Stickland NC (2007) A maternal ‘junk food’ diet in pregnancy and lactation promotes an exacerbated taste for ‘junk food’ and a greater propensity for obesity in rat offspring. Br J Nutr 98(4):843–851

    Article  CAS  PubMed  Google Scholar 

  25. Shalev U, Tylor A, Schuster K, Frate C, Tobin S, Woodside B (2010) Long-term physiological and behavioral effects of exposure to a highly palatable diet during the perinatal and post-weaning periods. Physiol Behav 101(4):494–502

    Article  CAS  PubMed  Google Scholar 

  26. Naef L, Moquin L, Dal Bo G, Giros B, Gratton A, Walker CD (2011) Maternal high-fat intake alters presynaptic regulation of dopamine in the nucleus accumbens and increases motivation for fat rewards in the offspring. Neuroscience 176:225–236

    Article  CAS  PubMed  Google Scholar 

  27. Jones SR, Gainetdinov RR, Wightman RM, Caron MG (1998) Mechanisms of amphetamine action revealed in mice lacking the dopamine transporter. J Neurosci 18(6):1979–1986

    CAS  PubMed  Google Scholar 

  28. la Fleur SE, Vanderschuren LJ, Luijendijk MC, Kloeze BM, Tiesjema B, Adan RA (2007) A reciprocal interaction between food-motivated behavior and diet-induced obesity. Int J Obes (Lond) 31(8):1286–1294

    Article  Google Scholar 

  29. Hryhorczuk C, Florea M, Rodaros D, Poirier I, Daneault C, Des Rosiers C et al (2015) Dampened mesolimbic dopamine function and signaling by saturated but not monounsaturated dietary lipids. Neuropsychopharmacology 41:811–821. doi:10.1038/npp.2015.207, Published online 5 Aug 2015

    Article  PubMed  Google Scholar 

  30. Davis JF, Tracy AL, Schurdak JD, Tschop MH, Lipton JW, Clegg DJ et al (2008) Exposure to elevated levels of dietary fat attenuates psychostimulant reward and mesolimbic dopamine turnover in the rat. Behav Neurosci 122(6):1257–1263, Pubmed Central PMCID: 2597276

    Article  PubMed  PubMed Central  Google Scholar 

  31. Sharma S, Fernandes MF, Fulton S (2013) Adaptations in brain reward circuitry underlie palatable food cravings and anxiety induced by high-fat diet withdrawal. Int J Obes (Lond) 37(9):1183–1191

    Article  CAS  Google Scholar 

  32. Ahima RS, Flier JS (2000) Leptin. Annu Rev Physiol 62:413–437

    Article  CAS  PubMed  Google Scholar 

  33. Kautzky-Willer A, Pacini G, Tura A, Bieglmayer C, Schneider B, Ludvik B et al (2001) Increased plasma leptin in gestational diabetes. Diabetologia 44(2):164–172

    Article  CAS  PubMed  Google Scholar 

  34. Masuyama H, Hiramatsu Y (2012) Effects of a high-fat diet exposure in utero on the metabolic syndrome-like phenomenon in mouse offspring through epigenetic changes in adipocytokine gene expression. Endocrinology 153(6):2823–2830

    Article  CAS  PubMed  Google Scholar 

  35. Sun B, Purcell RH, Terrillion CE, Yan J, Moran TH, Tamashiro KL (2012) Maternal high-fat diet during gestation or suckling differentially affects offspring leptin sensitivity and obesity. Diabetes 61(11):2833–2841, Pubmed Central PMCID: 3478561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. El-Haschimi K, Pierroz DD, Hileman SM, Bjorbaek C, Flier JS (2000) Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity. J Clin Invest 105(12):1827–1832, Pubmed Central PMCID: 378516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Hommel JD, Trinko R, Sears RM, Georgescu D, Liu ZW, Gao XB et al (2006) Leptin receptor signaling in midbrain dopamine neurons regulates feeding. Neuron 51(6):801–810

    Article  CAS  PubMed  Google Scholar 

  38. Fulton S, Pissios P, Manchon RP, Stiles L, Frank L, Pothos EN et al (2006) Leptin regulation of the mesoaccumbens dopamine pathway. Neuron 51(6):811–822

    Article  CAS  PubMed  Google Scholar 

  39. Sullivan EL, Nousen EK, Chamlou KA (2014) Maternal high fat diet consumption during the perinatal period programs offspring behavior. Physiol Behav 123:236–242, Pubmed Central PMCID: 3594403

    Article  CAS  PubMed  Google Scholar 

  40. Sullivan EL, Grayson B, Takahashi D, Robertson N, Maier A, Bethea CL et al (2010) Chronic consumption of a high-fat diet during pregnancy causes perturbations in the serotonergic system and increased anxiety-like behavior in nonhuman primate offspring. J Neurosci 30(10):3826–3830, Pubmed Central PMCID: 2846411, Epub 2010/03/12. eng

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. O'Reilly JR, Reynolds RM (2013) The risk of maternal obesity to the long-term health of the offspring. Clin Endocrinol (Oxf) 78(1):9–16

    Article  Google Scholar 

  42. Bilbo SD, Tsang V (2010) Enduring consequences of maternal obesity for brain inflammation and behavior of offspring. FASEB J 24(6):2104–2115

    Article  CAS  PubMed  Google Scholar 

  43. Peleg-Raibstein D, Luca E, Wolfrum C (2012) Maternal high-fat diet in mice programs emotional behavior in adulthood. Behav Brain Res 233(2):398–404

    Article  CAS  PubMed  Google Scholar 

  44. Sullivan EL, Smith MS, Grove KL (2011) Perinatal exposure to high-fat diet programs energy balance, metabolism and behavior in adulthood. Neuroendocrinology 93(1):1–8, Pubmed Central PMCID: 3700139

    Article  CAS  PubMed  Google Scholar 

  45. Gariepy G, Nitka D, Schmitz N (2010) The association between obesity and anxiety disorders in the population: a systematic review and meta-analysis. Int J Obes (Lond) 34(3):407–419

    Article  CAS  Google Scholar 

  46. Grissom NM, George R, Reyes TM (2015) The hypothalamic transcriptional response to stress is severely impaired in offspring exposed to adverse nutrition during gestation. Neuroscience. 2015 Jul 26. pii: S0306-4522(15)00636-3. doi:10.1016/j.neuroscience.2015.07.022

    Google Scholar 

  47. D’Asti E, Long H, Tremblay-Mercier J, Grajzer M, Cunnane SC, Di Marzo V et al (2010) Maternal dietary fat determines metabolic profile and the magnitude of endocannabinoid inhibition of the stress response in neonatal rat offspring. Endocrinology 151(4):1685–1694

    Article  PubMed  Google Scholar 

  48. Welberg LA, Seckl JR (2001) Prenatal stress, glucocorticoids and the programming of the brain. J Neuroendocrinol 13(2):113–128

    Article  CAS  PubMed  Google Scholar 

  49. Brunton PJ (2010) Resetting the dynamic range of hypothalamic-pituitary-adrenal axis stress responses through pregnancy. J Neuroendocrinol 22(11):1198–1213

    Article  CAS  PubMed  Google Scholar 

  50. Joels M, Karst H, DeRijk R, de Kloet ER (2008) The coming out of the brain mineralocorticoid receptor. Trends Neurosci 31(1):1–7

    Article  CAS  PubMed  Google Scholar 

  51. Grayson BE, Kievit P, Smith MS, Grove KL (2010) Critical determinants of hypothalamic appetitive neuropeptide development and expression: species considerations. Front Neuroendocrinol 31(1):16–31, Pubmed Central PMCID: 2813940

    Article  CAS  PubMed  Google Scholar 

  52. Sivanathan S, Thavartnam K, Arif S, Elegino T, McGowan PO (2015) Chronic high fat feeding increases anxiety-like behaviour and reduces transcript abundance of glucocorticoid signalling genes in the hippocampus of female rats. Behav Brain Res 286:265–270

    Article  CAS  PubMed  Google Scholar 

  53. Sharma S, Fulton S (2013) Diet-induced obesity promotes depressive-like behaviour that is associated with neural adaptations in brain reward circuitry. Int J Obes (Lond) 37(3):382–389

    Article  CAS  Google Scholar 

  54. Tannenbaum BM, Brindley DN, Tannenbaum GS, Dallman MF, McArthur MD, Meaney MJ (1997) High-fat feeding alters both basal and stress-induced hypothalamic-pituitary-adrenal activity in the rat. Am J Physiol 273(6 Pt 1):E1168–E1177

    CAS  PubMed  Google Scholar 

  55. Lindqvist A, Mohapel P, Bouter B, Frielingsdorf H, Pizzo D, Brundin P et al (2006) High-fat diet impairs hippocampal neurogenesis in male rats. Eur J Neurol 13(12):1385–1388

    Article  CAS  PubMed  Google Scholar 

  56. Buchenauer T, Behrendt P, Bode FJ, Horn R, Brabant G, Stephan M et al (2009) Diet-induced obesity alters behavior as well as serum levels of corticosterone in F344 rats. Physiol Behav 98(5):563–569

    Article  CAS  PubMed  Google Scholar 

  57. Auvinen HE, Romijn JA, Biermasz NR, Havekes LM, Smit JW, Rensen PC et al (2011) Effects of high fat diet on the Basal activity of the hypothalamus-pituitary-adrenal axis in mice: a systematic review. Horm Metab Res 43(13):899–906

    Article  CAS  PubMed  Google Scholar 

  58. Legendre A, Harris RB (2006) Exaggerated response to mild stress in rats fed high-fat diet. Am J Physiol Regul Integr Comp Physiol 291(5):R1288–R1294

    Article  CAS  PubMed  Google Scholar 

  59. Nestler EJ (2005) Is there a common molecular pathway for addiction? Nat Neurosci 8(11):1445–1449

    Article  CAS  PubMed  Google Scholar 

  60. Catalano PM (2007) Management of obesity in pregnancy. Obstet Gynecol 109(2 Pt 1):419–433

    Article  PubMed  Google Scholar 

  61. Cedar H, Bergman Y (2009) Linking DNA methylation and histone modification: patterns and paradigms. Nat Rev Genet 10(5):295–304

    Article  CAS  PubMed  Google Scholar 

  62. McGowan PO, Suderman M, Sasaki A, Huang TC, Hallett M, Meaney MJ et al (2011) Broad epigenetic signature of maternal care in the brain of adult rats. PLoS One 6(2):e14739, Pubmed Central PMCID: 3046141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Pan P, Fleming AS, Lawson D, Jenkins JM, McGowan PO (2014) Within- and between-litter maternal care alter behavior and gene regulation in female offspring. Behav Neurosci 128(6):736–748

    Article  PubMed  Google Scholar 

  64. Dudley KJ, Sloboda DM, Connor KL, Beltrand J, Vickers MH (2011) Offspring of mothers fed a high fat diet display hepatic cell cycle inhibition and associated changes in gene expression and DNA methylation. PLoS One 6(7):e21662, Pubmed Central PMCID: 3133558

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Jiang M, Zhang Y, Liu M, Lan MS, Fei J, Fan W et al (2011) Hypermethylation of hepatic glucokinase and L-type pyruvate kinase promoters in high-fat diet-induced obese rats. Endocrinology 152(4):1284–1289

    Article  CAS  PubMed  Google Scholar 

  66. Palou M, Pico C, McKay JA, Sanchez J, Priego T, Mathers JC et al (2011) Protective effects of leptin during the suckling period against later obesity may be associated with changes in promoter methylation of the hypothalamic pro-opiomelanocortin gene. Br J Nutr 106(5):769–778

    Article  CAS  PubMed  Google Scholar 

  67. Attig L, Vige A, Gabory A, Karimi M, Beauger A, Gross MS et al (2013) Dietary alleviation of maternal obesity and diabetes: increased resistance to diet-induced obesity transcriptional and epigenetic signatures. PLoS One 8(6):e66816, Pubmed Central PMCID: 3691260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Youngson NA, Morris MJ (2013) What obesity research tells us about epigenetic mechanisms. Philos Trans R Soc Lond Ser B Biol Sci 368(1609):20110337, Pubmed Central PMCID: 3539363

    Article  Google Scholar 

  69. Petronis A (2010) Epigenetics as a unifying principle in the aetiology of complex traits and diseases. Nature 465(7299):721–727

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Cell and Systems Biology, University of Toronto, 1265 Military Trail, Toronto, ON, Canada, M1C 1A4

    Aya Sasaki, Suzanne Erb & Patrick O. McGowan

  2. Department of Psychology, University of Toronto, Scarborough, 1265 Military Trail, Toronto, ON, Canada, M1C 1A4

    Aya Sasaki, Suzanne Erb & Patrick O. McGowan

  3. Department of Biological Sciences; Department of Physiology; Center for Environmental Epigenetics and Development, University of Toronto, Scarborough, 1265 Military Trail, Toronto, ON, Canada, M1C 1A4

    Patrick O. McGowan

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  1. Aya Sasaki
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  2. Suzanne Erb
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  3. Patrick O. McGowan
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Correspondence to Suzanne Erb or Patrick O. McGowan .

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Editors and Affiliations

  1. Institute of Developmental Sciences, University of Southampton, Southampton, Hampshire, United Kingdom

    Lucy R. Green

  2. Medical Center, The University of Mississippi, Jackson, Mississippi, USA

    Robert L. Hester

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Sasaki, A., Erb, S., McGowan, P.O. (2016). The Effect of Maternal Overnutrition on Reward and Anxiety in Offspring. In: Green, L., Hester, R. (eds) Parental Obesity: Intergenerational Programming and Consequences. Physiology in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-6386-7_9

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