Recent findings from human and animal studies indicate that maternal
undernutrition or
overnutrition affects covalent modifications of the fetal genome and its associated
histones that can be carried forward to subsequent generations. An adverse outcome of maternal
malnutrition is the development of
metabolic syndrome, which is defined as a cluster of disorders including
obesity,
hyperglycemia,
hyperinsulinemia,
hyperlipidemia,
hypertension and
insulin resistance. The transgenerational impacts of maternal nutrition are known as fetal programming, which is mediated by stable and heritable alterations of gene expression through covalent modifications of
DNA and
histones without changes in DNA sequences (namely, epigenetics). The underlying mechanisms include chromatin remodeling, DNA methylation (occurring at the 5'-position of
cytosine residues within CpG dinucleotides), histone modifications (acetylation, methylation, phosphorylation, ubiquitination and sumoylation) and expression and activity of small noncoding RNAs. The
enzymes catalyzing these reactions include
S-adenosylmethionine-dependent
DNA and
protein methyltransferases,
DNA demethylases, histone acetylase (
lysine acetyltransferase), general control nonderepressible 5 (GCN5)-related N-
acetyltransferase (a superfamily of
acetyltransferase) and
histone deacetylase.
Amino acids (e.g.,
glycine,
histidine,
methionine and
serine) and
vitamins (B6, B12 and
folate) play key roles in provision of methyl donors for
DNA and
protein methylation. Therefore, these nutrients and related metabolic pathways are of interest in dietary treatment of
metabolic syndrome. Intervention strategies include targeting epigenetically disturbed metabolic pathways through dietary supplementation with nutrients (particularly functional
amino acids and
vitamins) to regulate one-
carbon-unit metabolism, antioxidative reactions and gene expression, as well as
protein methylation and acetylation. These mechanism-based approaches may effectively improve health and well-being of affected offspring.