RESUMEN
BACKGROUND: Early nutritional challenges can lead to permanent metabolic changes, increasing risk for developing chronic diseases later in life. Total parenteral nutrition (TPN) is a life-saving nutrition regimen, used especially in intrauterine growth-restricted (IUGR) neonates. Early TPN feeding alters metabolism, but whether these alterations are permanent is unclear. Programmed metabolism is likely caused by epigenetic changes due to imbalances of methyl nutrients. OBJECTIVES: We sought to determine whether feeding TPN in early life would increase the risk of developing dyslipidemia in adulthood and whether supplementing the methyl nutrients betaine and creatine to TPN would prevent this development. We also sought to determine whether IUGR exacerbates the effects of neonatal TPN on lipid metabolism in adulthood. METHODS: Female piglets (n=32, 7 d old) were used in four treatments: 24 normal weight piglets were randomized to sow-fed (SowFed), standard TPN (TPN-control), and TPN with betaine and creatine (TPN-B+C); 8 IUGR piglets were fed control TPN (TPN-IUGR) as a fourth group. After 2 weeks of treatment, all pigs were then fed a standard solid diet. At 8 mo old, central venous catheters were implanted to conduct postprandial fat tolerance tests. RESULTS: Feeding TPN in the neonatal period led to dyslipidemia in adulthood, as indicated by higher postprandial triglyceride (TG) levels in TPN-control (P<0.05), compared to SowFed. IUGR piglets were particularly sensitive to neonatal TPN feeding, as TPN-IUGR piglets developed obesity and dyslipidemia in adulthood, as indicated by greater backfat thickness (P<0.05), higher liver TG (P<0.05), slower postprandial TG clearance (P<0.05), and elevated fasting plasma non-high density lipoprotein (HDL)-cholesterol (P<0.01), and non-esterified fatty acids (NEFA) (P<0.001), compared to TPN-control. CONCLUSIONS: Feeding TPN in early life increases the risk of developing dyslipidemia in adulthood, especially in IUGR neonates; however, methyl nutrient supplementation to TPN did not prevent TPN-induced changes in lipid metabolism.
RESUMEN
The risk for non-communicable diseases in adulthood can be programmed by early nutrition. This programming is mediated by changes in expression of key genes in various metabolic pathways during development, which persist into adulthood. These developmental modifications of genes are due to epigenetic alterations in DNA methylation patterns. Recent studies have demonstrated that DNA methylation can be affected by maternal or early postnatal diets. Because methyl groups for methylation reactions come from methionine cycle nutrients (i.e., methionine, choline, betaine, folate), deficiency or supplementation of these methyl nutrients can directly change epigenetic regulation of genes permanently. Although many studies have described the early programming of adult diseases by maternal and infant nutrition, this review discusses studies that have associated early dietary methyl nutrient manipulation with direct effects on epigenetic patterns that could lead to chronic diseases in adulthood. The maternal supply of methyl nutrients during gestation and lactation can alter epigenetics, but programming effects vary depending on the timing of dietary intervention, the type of methyl nutrient manipulated, and the tissue responsible for the phenotype. Moreover, the postnatal manipulation of methyl nutrients can program epigenetics, but more research is needed on whether this approach can rescue maternally programmed offspring.