title: Long-term programming effects of feeding total parenteral nutrition to Yucatan miniature pigs during the neonatal period
Creators: name: Randunu, Raniru S
Publisher: name: Memorial University of Newfoundland
publisherIdentifier: https://ror.org/04haebc03
publisherIdentifierScheme: ROR
Year: 2024

description: Early programming of adult diseases was initially described by Barker and colleagues and refers to long-term outcomes of nutritional or environmental insults in early life. Many epidemiological studies show a relationship between early nutrition and the risk of chronic diseases such as cardiovascular disease (CVD), type 2 diabetes, and metabolic syndrome. Changes in early nutrition during a critical period of life program the individual's health in adulthood, likely mediated via epigenetics. A key epigenetic mechanism is DNA methylation, and the availability of methyl nutrients during critical periods of early life is likely to alter the epigenome, thereby programming gene expression and risk for chronic diseases in adulthood. Metabolic syndrome is defined by the World Health Organization as a chronic pathogenic condition characterized by abdominal obesity, insulin resistance, hypertension, and dyslipidemia and has a high prevalence rate worldwide. Total parenteral nutrition (TPN) is a non-normal nutrition regimen given to infants who cannot tolerate oral feeding, commonly prescribed for preterm and intrauterine growth restricted (IUGR) infants as an essential part of medical management. Although TPN is a lifesaving feeding method, it exerts significant metabolic stress, and if this stress occurs during the epigenetic ‘window’ of programming, the metabolism can be programmed and increase the risk of adult diseases. Thus, modulation of methyl nutrientsin TPN to prevent epigenetic programming and reduce the risk of adult diseases has great potential to improve the quality of life in infants who need TPN in early life as a life-saving measure. Although there is a wealth of knowledge on developmental programming, the metabolic consequences of being IUGR, and the acute effects of TPN feeding, the long-term effects of feeding TPN to infants and IUGR neonates are unknown. We hypothesized that the metabolic effects of feeding TPN in early life would persist into adulthood, increasing the risk of developing metabolic syndrome and that supplementing betaine and creatine, which are novel ingredients in TPN, would prevent this development. Twenty-four female piglets (7 d old) were randomized to sow-fed (SowFed), TPN control (TPN-control), TPN with betaine and creatine (TPN-B+C); eight intrauterine growth restricted (TPN-IUGR) piglets fed TPN formed a fourth group. After 2 weeks of treatment, all pigs were fed a grower diet for 8 mo. At 9 mo, an arterial blood pressure telemeter and central venous catheters were implanted to conduct metabolic tests. TPN-IUGR pigs grew faster, and body measurements were not different among groups at 9 mo of age. Our findings indicate that feeding TPN in the neonatal period led to dyslipidemia in adulthood, as indicated by higher postprandial triglyceride (TG) levels in TPN�control pigs (P<0.05) compared to SF. Adding betaine and creatine to early TPN (TPN-BC) (to enhance methyl group availability) lowered mean arterial pressure (P<0.01) and systolic arterial pressure (P<0.01) in adulthood, compared to the TPN-control, thus reducing the risk of hypertension. IUGR piglets were particularly sensitive to TPN feeding effects as TPN- IUGR led to development of obesity and dyslipidemia in adulthood as revealed by a higher backfat thickness (P<0.05), elevated fasting non-HDL cholesterol (P<0.01), higher fasting non-esterified fatty acids (P<0.001), higher liver TG (P<0.05) and slower postprandial TG clearance (P<0.05) compared to TPN-control. Collectively, these data suggest feeding TPN in early life increases the risk for the development of biomarkers of metabolic syndrome in adulthood, especially in IUGR neonates, and supplementing betaine and creatine to TPN might reduce this risk.