Choice of Lipid Emulsion Determines Inflammation of the Gut‐Liver Axis, Incretin Profile, and Insulin Signaling in a Murine Model of Total Parenteral Nutrition

Abstract

Scope The aim of this study was to test whether the choice of the lipid emulsion in total parenteral nutrition (TPN), i.e. n‐3 fatty acid‐based Omegaven versus n‐6 fatty acid‐based Intralipid, determines inflammation in the liver, the incretin profile, and insulin resistance. Methods and Results Jugular vein catheters (JVC) were placed in C57BL/6 mice and used for TPN for seven days. Mice were randomized into a saline group (saline infusion with oral chow), an Intralipid group (IL‐TPN, no chow), an Omegaven group (OV‐TPN, no chow), or a chow only group (without JVC). Both TPN elicited higher abundance of lipopolysaccharide binding protein in the liver, but only IL‐TPN increased interleukin‐6 and interferon‐γ, while OV‐TPN reduced interleukin‐4, monocyte chemoattractant protein‐1, and interleukin‐1ɑ. Insulin plasma concentrations were higher in both TPN, while glucagon and GLP1 were higher in IL‐TPN. Gluconeogenesis was increased in IL‐TPN and the nuclear profile of key metabolic transcription factors showed a liver‐protective phenotype in OV‐TPN. OV‐TPN increased insulin sensitivity in the liver and skeletal muscle. Conclusions OV‐TPN as opposed to IL‐TPN mitigates inflammation in the liver and reduces the negative metabolic effects of hyperinsulinemia and hyperglucagonemia by “re‐sensitizing” the liver and skeletal muscle to insulin. This article is protected by copyright. All rights reserved