Chronic parenteral nutrition induces hepatic inflammation, steatosis, and insulin resistance in neonatal pigs

Barbara Stoll, David A. Horst, Liwei Cui, Xiaoyan Chang, Kenneth J. Ellis, Darryl L. Hadsell, Agus Suryawan, Ashish Kurundkar, Akhil Maheshwari, Teresa A. Davis, Douglas G. Burrin

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Abstract

Prematurity and overfeeding in infants are associated with insulin resistance in childhood and may increase the risk of adult disease. Total parenteral nutrition (TPN) is a major source of infant nutritional support and may influence neonatal metabolic function. Our aim was to test the hypothesis that TPN induces increased adiposity and insulin resistance compared with enteral nutrition (EN) in neonatal pigs. Neonatal pigs were either fed enteral formula orally or i.v. administered a TPN mixture for 17 d; macronutrient intake was similar in both groups. During the 17-d period, we measured body composition by dual-energy X-ray absorptiometry scanning; fasting i.v. glucose tolerance tests (IVGTT) and hyperinsulinemic-euglycemic clamps (CLAMP) were performed to quantify insulin resistance. On d 17, tissue was collected after 1-h, low-dose CLAMP for tissue insulin signaling assays. TPN pigs gained less lean andmore body fat and developed hepatic steatosis compared with EN pigs. After 7 and 13 d, IVGTT showed evidence of insulin resistance in the TPN compared with the EN group. Fasting plasma glucose and insulin also were higher in TPN pigs. CLAMP showed that insulin sensitivity was markedly lower in TPN pigs than in EN pigs. TPN also reduced the abundance of the insulin receptor, insulin receptor substrate 1, and phosphatidylinositol 3 kinase in skeletal muscle and liver and the proliferation of total pancreatic cells and β-cells. Hepatic proinflammatory genes as well as c-Jun-N-terminal kinase 1 phosphorylation, plasma interleukin 6, and tumor necrosis factor-α were all higher in TPN pigs than in EN pigs. The results demonstrate that chronic TPN induces a hepatic inflammatory response that is associated with significant insulin resistance, hepatic steatosis, and fat deposition compared with EN in neonatal pigs. Further studies are warranted to establish the mechanism of TPN-induced insulin resistance and hepatic metabolic dysfunction and whether there are persistent metabolic consequences of this lifesaving form of infant nutritional support.

Original languageEnglish (US)
Pages (from-to)2193-2200
Number of pages8
JournalJournal of Nutrition
Volume140
Issue number12
DOIs
StatePublished - Dec 1 2010

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ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Stoll, B., Horst, D. A., Cui, L., Chang, X., Ellis, K. J., Hadsell, D. L., Suryawan, A., Kurundkar, A., Maheshwari, A., Davis, T. A., & Burrin, D. G. (2010). Chronic parenteral nutrition induces hepatic inflammation, steatosis, and insulin resistance in neonatal pigs. Journal of Nutrition, 140(12), 2193-2200. https://doi.org/10.3945/jn.110.125799