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Maternal Undernutrition and Long-Term Effects on Hepatic Function

  • Chapter
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Diet, Nutrition, and Fetal Programming

Part of the book series: Nutrition and Health ((NH))

Abstract

Undernutrition in utero, regardless of the source, can impair proper liver development leading to long-term metabolic dysfunction. Understanding the molecular mechanisms underlying how nutritional deficits during perinatal life lead to permanent alterations in hepatic gene expression will provide better therapeutic strategies to alleviate the undernourished liver in postnatal life. This chapter addresses the different experimental models of undernutrition in utero and highlights the direct and indirect mechanisms involved leading to metabolic diseases in the liver. These include hypoxia, oxidative stress, epigenetic alterations, and endoplasmic reticulum (ER) stress. In addition, promising perinatal nutritional and pharmaceutical interventions are highlighted which illustrate how the placidity of the developing liver can be exploited to prevent the onset of long-term metabolic disease.

Supported by: CIHR Operating Grant and Natural Sciences and Engineering Research Council of Canada.

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Abbreviations

11β-HSD1:

11β-hydroxysteroid dehydrogenase type 1

ADP:

Adenine diphosphate

Akt1:

Protein kinase B

CpG:

Cysteine-phosphate-guanine

CVD:

Cardiovascular disease

Cyp2c11:

Cytochrome P450 2c11

Cyp3a1:

Cytochrome P450 3a1

Cyp7a1:

Cytochrome P450 7a1

EPO:

Erythropoietin

ER stress:

Endoplasmic reticulum stress

Ex-4:

Exendin-4

G6Pase:

Glucose-6 phosphatase

GLP-1:

Glucagon-like peptide-1

GR:

Glucocorticoid receptor

HDL:

High-density lipoproteins

IGF-1:

Insulin growth factor 1

IUGR:

Intrauterine growth restriction

JMJD:

Jmj domain-containing histone demethylation protein

LDL:

Low-density lipoproteins

LP:

Low protein

LXR:

Liver X receptor

miRs:

MicroRNAs

MMP2:

Matrix metalloproteinase 2

MNR:

Maternal nutrition restriction

MPR:

Maternal protein restriction

pAkt1 (Ser473):

Phospho Akt1 (serine 473)

Pck1:

Phosphoenolpyruvate carboxykinase 1 (soluble)

pEIF2α:

Phospho-eukaryotic translation initiation factor 2

PND:

Postnatal day

PPAR:

Peroxisome proliferator-activated receptor

SGA:

Small for gestational age

SMAD4:

SMAD family member 4

TGFB1:

Transforming growth factor β1

TUDCA:

Tauroursodeoxycholic acid

UPR:

Unfolded protein response

VEGF:

Vascular endothelial growth factor

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Authors and Affiliations

  1. The Departments of Obstetrics & Gynecology and Physiology & Pharmacology, The Children’s Health Research Institute and the Lawson Health Research Institute, The University of Western Ontario, London, ON, Canada

    Daniel B. Hardy PhD

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  1. Daniel B. Hardy PhD
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Correspondence to Daniel B. Hardy PhD .

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Editors and Affiliations

  1. Department of Nutrition, King's College, London, United Kingdom

    Rajkumar Rajendram

  2. Department of Nutrition, King's College, London, United Kingdom

    Victor R. Preedy

  3. Department of Biomedical Sciences, University of Westminster, London, United Kingdom

    Vinood B. Patel

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Hardy, D.B. (2017). Maternal Undernutrition and Long-Term Effects on Hepatic Function. In: Rajendram, R., Preedy, V., Patel, V. (eds) Diet, Nutrition, and Fetal Programming. Nutrition and Health. Humana Press, Cham. https://doi.org/10.1007/978-3-319-60289-9_9

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