Adverse metabolic phenotypes in parenterally fed neonatal pigs do not persist into adolescence

Authors: ELEFSON, SARAH - Baylor College Of Medicine; STOLL, BARBARA - Baylor College Of Medicine; DAVIS, TERESA - Baylor College Of Medicine; FIOROTTO, MARTA - Baylor College Of Medicine; EL KADI, SAMER - Virginia Tech; Genovese, Kenneth - Ken; THYMANN, THOMAS - University Of Copenhagen; SANGILD, PER - University Of Copenhagen; Burrin, Douglas - Doug

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/28/2023
Publication Date: 2/1/2024
Citation: Elefson, S.K., Stoll, B., Davis, T., Fiorotto, M.L., El Kadi, S.W., Genovese, K.J., Thymann, T., Sangild, P.T., Burrin, D.G. 2024. Adverse metabolic phenotypes in parenterally fed neonatal pigs do not persist into adolescence. Journal of Nutrition. 154(2):638-647. https://doi.org/10.1016/j.tjnut.2023.12.048.
DOI: https://doi.org/10.1016/j.tjnut.2023.12.048

Interpretive Summary: Newborn infants will receive total parenteral nutrition (TPN), or nutrients administered via i.v., to meet nutritional requirements when they are unable to consume food normally. Barker's hypothesis states that what happens to infants during pregnancy and/or early life will affect the individual later in life, thus we wanted to investigate if TPN during infancy will lead to negative effects in adulthood. Specifically, this study looks at whether TPN will lead to the development of obesity and glucose intolerance. We administered TPN for two weeks to one group of newborn pigs, while the control group received infant formula. Both groups of pigs were then moved to a diet of solid food, which was high in fat and sugar for 126 days. We measured percent body fat and lean periodically over this time and gave a glucose intolerance test at the end of the study. This allowed us to compare if the pigs that received TPN became more obese or developed glucose intolerance compared to the control pigs. We found that pigs that received TPN pigs had a higher percent body fat on day 45 of the study, but at the end of the study percent body fat was the same for both groups of pigs. We also found that TPN pigs were able to clear glucose better than the control pigs. We also did not see any liver fat accumulation or injury. Our results suggest that if TPN is given to infants, obesity may develop temporarily, but this does not last into adulthood, nor does TPN lead to the development of glucose intolerance.

Technical Abstract: Nutrition during fetal and neonatal life is an important determinant for the risk of adult-onset diseases, especially type 2 diabetes and obesity. We aimed to determine whether total parenteral nutrition (TPN) compared with enteral formula feeding [enteral nutrition (EN)] in term piglets during the first 2 wk after birth would increase the long-term (5-mo) development of metabolic syndrome phenotypes with adverse glucose homeostasis, fatty liver disease, and obesity. Neonatal female pigs were administered TPN (n=12) or fed enterally with a liquid enteral milk-replacer formula (EN, n=12) for 14 d. After transitioning TPN pigs to enteral feeding of liquid formula (days 15-26), both groups were adapted to a solid high-fat diet (30% of the total diet) and sucrose (20% of the total diet) diet (days 27-33), which was fed until the end of the study (140 d). Body composition was measured by dual-energy X-ray absorptiometry at 14, 45, and 140 d. Serum biochemistry and glucose-insulin values (after a fasting intravenous glucose tolerance test) were obtained at 140 d. Liver and muscle were analyzed for insulin receptor signaling and triglycerides. Body weight was similar, but percent fat was higher, whereas percent lean and bone mineral density were lower in TPN than in EN pigs (P<0.01) at 45 d of age but not at 140 d. At 140 d, there were no differences in serum markers of liver injury or lipidemia. Intravenous glucose tolerance test at 140 d showed a lower (P<0.05) AUC for both glucose and insulin in TPN than in EN pigs, but the ratio of AUCs of insulin and glucose was not different between groups. Administration of TPN during the neonatal period increased adipose deposition that transiently persisted in early adolescence when challenged with a high-fat diet but was not sustained or manifested as glucose intolerance.