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Perinatal Malnutrition and Epigenetic Regulation of Long-Term Metabolism

  • Daniel B. Hardy
Reference work entry

Abstract

Maternal malnutrition in perinatal life can have long-lasting adverse effects on glucose and lipid homeostasis in the offspring, culminating in dyslipidemia, insulin resistance, and obesity. Understanding the molecular mechanisms underlying how these nutritional deficits during perinatal life lead to permanent changes in hepatic and adipose function will provide efficacious therapeutic strategies to mitigate these metabolic defects short and long term. This chapter addresses how epigenetic mechanisms mediate alterations in hepatic and adipose gene expression identified from clinical studies and different experimental models of maternal malnutrition. These include DNA methylation, posttranslational histone modifications, and microRNAs.

Keywords

DOHaD Dyslipidemia Maternal low-protein diet Liver Adipose Obesity Plasticity Sexual dimorphism Posttranslational histone modifications DNA methylation MicroRNAs 

List of Abbreviations

11β-HSD1

11β-hydroxysteroid dehydrogenase type 1

ABCA1

ATP-binding cassette transporter 1

ABCG5/8

ATP-binding cassette transporter 5/8

ACCα

Acetyl-CoA carboxylase-α

ADP

Adenine diphosphate

APOE

Apolipoprotein E

CpG

Cysteine-phosphate-guanine

CVD

Cardiovascular disease

Cyp7a1

Cytochrome P450 7a1

DOHaD

Developmental origins of health and disease

ER stress

Endoplasmic reticulum stress

FBPase

Fructose bisphosphatase

G6Pase

Glucose-6 phosphatase

GDF3

Growth differentiation factor-3

HDL

High-density lipoprotein

HMG-COA

3-hydroxy-3-methylglutaryl-coenzyme A

HNF4α

Hepatocyte nuclear factor 4α

IGF-1

Insulin growth factor 1

IGF-2R

Insulin growth factor 2 receptor

IUGR

Intrauterine growth restriction

JMJD

Jmj-domain-containing histone demethylation protein

LDL

Low-density lipoproteins

LP

Low protein

LXR

Liver X receptor

LXRE

Liver X receptor element

miRs

MicroRNAs

MPR

Maternal protein restriction

PCK1

Phosphoenolpyruvate carboxykinase 1 (soluble)

PEPCK

Phosphoenolpyruvate carboxykinase

PND

Postnatal day

SCD-1

Stearoyl-CoA desaturase

SMAD4

SMAD family member 4

WAT

White adipose tissue

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Authors and Affiliations

  1. 1.Departments of Obstetrics and Gynecology and Physiology and Pharmacology, The Children’s Health Research Institute and The Lawson Health Research InstituteThe University of Western OntarioLondonCanada

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