Epigenetic Mechanisms of Maternal Obesity Effects on the Descendants

  • Paul Cordero
  • Jiawei Li
  • Jonathan L. Temple
  • Vi Nguyen
  • Jude A. Oben
Chapter
Part of the Physiology in Health and Disease book series (PIHD)

Abstract

Obesity has been described as a pandemic of the twenty-first century. Its prevalence among women of childbearing age continues to rise, increasing the risk of complications during pregnancy and the likelihood of their offspring developing obesity and its comorbidities in adult life. As our understanding of the developmental origins of health and disease has grown, the influence of maternal perinatal physiology has become more clear. Maternal programming appears to be shaped by epigenetic means. Diverse communities of epigenetic modifications determine the phenotypic characteristics of different cell types and are themselves adaptable to changes in cellular physiology and environment. It is now thought that such epigenetic programs are potentially heritable. Maternal body mass and other obesogenic cues have been widely associated with epigenetic alterations of offspring in human observational studies. Similarly, interventional studies in rodents demonstrate that obesogenic maternal diet, as well as maternal diabetes and obesity, manifests epigenetic and phenotypic alterations in different organs, often in association with genes related to appetite, glycaemic control and lipid biosynthesis. Whilst the dangers posed by obesity to the health of our society are undeniable, the impact of obesity upon the health of our children is only just beginning to emerge. Recent evidence suggests that, in addition to the effects of epigenetic programming upon first generation offspring, subsequent generations may also be affected. A greater understanding of the molecular phenomenology underlying maternal epigenetic programming in obesity may well lead to the development of effective therapeutic interventions to combat this disease and its comorbidities.

Keywords

Epigenetics Obesity DNA methylation Histone Developmental programming Maternal obesity Transgenerational DOHaD Epigenotype 

List of Abbreviations

BMI

Body mass index

C/EBP-β

CCAAT/enhancer binding protein, beta

DOHaD

Developmental origins of health and disease

H19

H19, imprinted maternally expressed transcript

LINE-1

Long interspersed nuclear element 1

Mest

Mesoderm-specific transcript

NAFLD

Non-alcoholic fatty liver disease

NAFPD

Non-alcoholic fatty pancreas disease

NPY

Neuropeptide Y

Nr3c1

Nuclear receptor subfamily 3, group C, member 1

Peg3

Paternally expressed 3

POMC

Proopiomelanocortin

Ppargc1a

Peroxisome proliferator-activated receptor-gamma Co-activator 1-α

Ppar-α

Peroxisome proliferator activated receptor alpha

RXRA

Retinoid X receptor-α

TLR1

Toll-like receptor 1

TLR2

Toll-like receptor 2

Zfp423

Zinc finger protein 423

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Copyright information

© The American Physiological Society 2016

Authors and Affiliations

  • Paul Cordero
    • 1
  • Jiawei Li
    • 1
  • Jonathan L. Temple
    • 2
  • Vi Nguyen
    • 1
  • Jude A. Oben
    • 1
    • 3
  1. 1.Institute for Liver and Digestive HealthUniversity College London, Royal Free Hospital, NHS Foundation TrustLondonUK
  2. 2.Faculty of Life Sciences and MedicineKing’s College LondonLondonUK
  3. 3.Department of Gastroenterology and HepatologyGuy’s and St Thomas’ Hospital, NHS Foundation TrustLondonUK

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