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Fetal Programming of Fatty Liver Disease

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The Human Gut-Liver-Axis in Health and Disease

Abstract

Accumulation of fat in the hepatocytes also called non-alcoholic fatty liver disease (NAFLD) refers to a spectrum of liver disease ranging from simple fatty liver (steatosis), to nonalcoholic steatohepatitis (NASH) to liver cirrhosis. NAFLD is the most common liver disease in the world and the prevalence of NAFLD usually parallel that of obesity. NAFLD is caused by interactions between many environmental and genetic factors, and is associated with metabolic dysfunction including insulin resistance and dyslipidemia and is thus increasing the risk of type 2 diabetes (T2D).

The concept of fetal programming links the environmental conditions during fetal development with risk of diseases later in life. There is evidence that the liver is a target organ for programming and both fetal under- and overnutrition, may contribute to the development of obesity, hyperlipidemia, insulin resistance and T2D, all of which are closely associated with NAFLD.

Fetal programming can alter the epigenetic marks of the developing offspring and thus programming of organ defects. Epigenetic modifiers are involved in lipid metabolism, mitochondrial damage, oxidative stress, inflammation, among others, increasing the risk of hepatic lipid accumulation and of NAFLD. Therefore, studies of epigenetic changes and their roles in the pathogenesis of NAFLD could improve our understanding of molecular mechanisms underlying the association between fetal programming and fatty liver disease.

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Abbreviations

BMI:

Body mass index

DAG:

Diacylglycerol

DNL:

De novo lipogenesis

DXA:

Dual-energy X-ray absorptiometry

DOHaD:

Developmental Origins of Health and Disease

FFA:

Free fatty acids

GIP:

Glucose-dependent insulinotropic polypeptide

GLP-1:

Glucagon-like peptide-1

GLUT4:

Glucose transporter-4

GWA:

Genome-wide association

HBW:

High birth weight

IGT:

Impaired glucose tolerance

IMCL:

Intramyocellular lipids

IUGR:

Intrauterine growth restriction

LBW:

Low birth weight

NAFLD:

Nonalcoholic fatty liver disease

NASH:

Nonalcoholic steatohepatitis

NBW:

Normal birth weight

TG:

Triglycerides

T2D:

Type 2 diabetes

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Authors and Affiliations

  1. Department of Endocrinology (Diabetes and Metabolism), Rigshospitalet, Copenhagen, Denmark

    Charlotte Brøns

  2. Laboratory of Molecular Medicine, Department of Clinical Immunology, Sect. 7631, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

    Louise Justesen

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  1. Charlotte Brøns
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  2. Louise Justesen
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Correspondence to Charlotte Brøns .

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  1. Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark

    Aleksander Krag

  2. The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Copenhagen, Denmark

    Torben Hansen

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Brøns, C., Justesen, L. (2019). Fetal Programming of Fatty Liver Disease. In: Krag, A., Hansen, T. (eds) The Human Gut-Liver-Axis in Health and Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-98890-0_4

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