title: Fattening by deprivation: methyl balance and perinatal cardiomyopathy.
abstract: Folate deficiency during pregnancy is associated with reduced birth weight, and a low birth weight is associated with increased cardiometabolic risk in adulthood. In the study by Moreno Garcia, Guéant-Rodriguez and colleagues reported in the current issue of the Journal of Pathology, the effect of methyl group deprivation in pregnancy on the neonatal myocardium was investigated. By utilizing a diet deficient in folate, vitamin B(12) and choline, the authors created a significant deficit of methyl groups in the fetus. During the weaning period and the concomitant shift from the relative hypoxia and glucose dependence of the gestational period to the aerobic, milk-derived high-fat metabolic environment of the weaning phase, the offspring developed a myocardial hypertrophy associated with disordered fatty acid oxidation and mitochondrial dysfunction. The functionality of PGC-1α, a master regulator of metabolic pathways including mitochondrial energetics and fatty acid oxidation, was found to be reduced in the methyl-deprived group, due to an imbalance in the ratio of methylation to acetylation. This study demonstrates that maternal methyl deprivation could 'prime' the fetus by reducing its ability to oxidize fatty acids in the myocardium, thereby causing lipid accumulation and myocardial hypertrophy during exposure to high-fat diet in the weaning phase. This study has important implications for clinical perinatal cardiomyopathy and for the effect of maternal methyl group deprivation on the future risk of cardiovascular disease, and also potentially in enhancing the understanding of the elusive link between hyperhomocysteinaemic states in the adult and cardiovascular disease.
authors: VA Boston Healthcare System, West Roxbury, MA, USA. jjoseph16@partners.org
authors: Jacob
authors: J
authors: Joseph
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000209:etiology*; D005260:Female; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011484:Protein-Arginine N-Methyltransferases / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D056564:Sirtuin 1 / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D014804:Vitamin B Deficiency / Q000150:complications*
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C541817:PRMT1 protein, rat; D011484:Protein-Arginine N-Methyltransferases; C488368:Sirt1 protein, rat; D056564:Sirtuin 1