Intrauterine Growth-Restricted Female Yucatan Miniature Pig Neonates Fed Parenteral Nutrition Exhibit Early Catch-Up Growth Leading to Obesity and Ectopic Fat Deposition in Adulthood.

BACKGROUND: Total parenteral nutrition (TPN) is often used as a lifesaving nutritional regimen in intrauterine growth-restricted (IUGR) neonates. However, nutrition perturbations during the early critical period may permanently program metabolism via methyl-dependent epigenetic alterations that can lead to obesity and dyslipidemia in adulthood. Methyl group availability can be increased by adding betaine and creatine to TPN. OBJECTIVES: We sought to determine whether TPN in early life would have long-term effects on the development of obesity, whether IUGR will exacerbate these TPN-induced effects, and whether supplementing betaine and creatine to TPN will alleviate these effects. METHODS: Twenty four 7-d-old female piglets were randomly assigned to suckled, TPN-control diet (TPN-control), and TPN with betaine and creatine groups. Eight IUGR piglets were fed TPN (TPN-IUGR) as a fourth group. After 2 wk of TPN, all pigs received semi-restricted standard feed until adulthood (9 mo). Plasma and tissues were measured for lipids, hormones, and other metabolites associated with the development of obesity and metabolic syndrome. RESULTS: Growth rates of TPN-IUGR were 32% and 42% greater than TPN-control during the 1-4 mo and 4-6 mo periods, respectively (P < 0.05), indicating catch-up growth, which led to greater adiposity, as indicated by a 16% higher backfat thickness at 9 mo (P < 0.05). Moreover, TPN-IUGR pigs had 2.54-fold and 3.28-fold greater (P < 0.05) accumulation of ectopic triglyceride deposition in the liver and skeletal muscle, respectively, possibly due to 67% greater fasting plasma nonesterified fatty acids (P < 0.001). TPN-control was not different from suckled or TPN with betaine and creatine pigs, suggesting that feeding TPN during the neonatal period did not result in obesity later in life, and methyl nutrient supplementation to TPN had no effect on obesity. CONCLUSIONS: IUGR has a profound effect on developing obesity later in life, but TPN feeding does not lead to obesity in adulthood.