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Nutritional models of foetal programming and nutrigenomic and epigenomic dysregulations of fatty acid metabolism in the liver and heart

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Abstract

Barker’s concept of ‘foetal programming’ proposes that intrauterine growth restriction (IUGR) predicts complex metabolic diseases through relationships that may be further modified by the postnatal environment. Dietary restriction and deficit in methyl donors, folate, vitamin B12, and choline are used as experimental conditions of foetal programming as they lead to IUGR and decreased birth weight. Overfeeding and deficit in methyl donors increase central fat mass and lead to a dramatic increase of plasma free fatty acids (FFA) in offspring. Conversely, supplementing the mothers under protein restriction with folic acid reverses metabolic and epigenomic phenotypes of offspring. High-fat diet or methyl donor deficiency (MDD) during pregnancy and lactation produce liver steatosis and myocardium hypertrophy that result from increased import of FFA and impaired fatty acid β-oxidation, respectively. The underlying molecular mechanisms show dysregulations related with similar decreased expression and activity of sirtuin 1 (SIRT1) and hyperacetylation of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α). High-fat diet and overfeeding impair AMPK-dependent phosphorylation of PGC-1α, while MDD decreases PGC-1α methylation through decreased expression of PRMT1 and cellular level of S-adenosyl methionine. The visceral manifestations of metabolic syndrome are under the influence of endoplasmic reticulum (ER) stress in overnourished animal models. These mechanisms should also deserve attention in the foetal programming effects of MDD since vitamin B12 influences ER stress through impaired SIRT1 deacetylation of HSF1. Taken together, similarities and synergies of high-fat diet and MDD suggest, therefore, considering their consecutive or contemporary influence in the mechanisms of complex metabolic diseases.

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Abbreviations

AMPK:

AMP-activated protein kinase

Cbl:

Cobalamin

DAG:

Diacylglycerol

DMR:

Differentially methylated region

DNMT:

DNA (cytosine-5)-methyltransferase

ERR-α:

Oestrogen-related receptor alpha

FA:

Fatty acid

FAD:

Flavin adenine dinucleotide

FFA:

Free fatty acids

GCN5:

General control non-derepressible 5

GR:

Glucocorticoid receptor

HSF1:

Heat shock factor protein 1

HDAC:

Histone deacetylase

HDM:

Histone demethylase

HMT:

Histone methyltransferase

IGF1:

Insulin-like growth factor 1

IL-6:

Interleukin-6

IUGR:

Intrauterine growth restriction

MS:

Methionine synthase

MTHFR:

Methylenetetrahydrofolate reductase

MDD:

Methyl donor deficiency

mTOR:

Target of rapamycin

NAD+ :

Nicotinamide dinucleotide

NAFLD:

Non-alcoholic fatty liver disease

NASH:

Non-alcoholic steatohepatitis

OCM:

One-carbon metabolism

PPAR-α:

Peroxisome proliferator-activated receptor alpha

PGC-1α:

Peroxisome proliferator-activated receptor-γ coactivator 1α

POMC:

Preproopiomelanocortin

PRMT1:

Protein arginine methyltransferase 1

ROS:

Reactive oxygen species

SAM:

S-adenosyl methionine

SAH:

S-adenosyl homocysteine

5-HT:

Serotonin

SIRT:

Sirtuins

SREBP1c:

Sterol response element binding protein 1c

SAT:

Subcutaneous adipose tissue

TNF-α:

Tumour necrosis factor-alpha

T2DM:

Type 2 diabetes mellitus

VAT:

Visceral adipose tissue

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    Jean-Louis Guéant, Rania Elakoum, Olivier Ziegler, David Coelho, Eva Feigerlova, Jean-Luc Daval & Rosa-Maria Guéant-Rodriguez

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Correspondence to Jean-Louis Guéant.

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Guéant, JL., Elakoum, R., Ziegler, O. et al. Nutritional models of foetal programming and nutrigenomic and epigenomic dysregulations of fatty acid metabolism in the liver and heart. Pflugers Arch - Eur J Physiol 466, 833–850 (2014). https://doi.org/10.1007/s00424-013-1339-4

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  • DOI: https://doi.org/10.1007/s00424-013-1339-4

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