Choice of Lipid Emulsion Determines Inflammation of the Gut-Liver Axis, Incretin Profile, and Insulin Signaling in a Murine Model of Total Parenteral Nutrition
- 1 March 2021
- journal article
- research article
- Published by Wiley in Molecular Nutrition & Food Research
- Vol. 65 (5), e2000412
- https://doi.org/10.1002/mnfr.202000412
Abstract
Scope The aim of this study is to test whether the choice of the lipid emulsion in total parenteral nutrition (TPN), that is, 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) are placed in C57BL/6 mice and used for TPN for 7 days. Mice are 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 elicite higher abundance of lipopolysaccharide binding protein in the liver, but only IL-TPN increases interleukin-6 and interferon-gamma, while OV-TPN reduces interleukin-4, monocyte chemoattractant protein-1, and interleukin-1 alpha. Insulin plasma concentrations are higher in both TPN, while glucagon and glucagon-like peptide-1 (GLP-1) were higher in IL-TPN. Gluconeogenesis is increased in IL-TPN and the nuclear profile of key metabolic transcription factors shows a liver-protective phenotype in OV-TPN. OV-TPN increases insulin sensitivity in the liver and skeletal muscle. Conclusion 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 publication has 66 references indexed in Scilit:
- Regulation of FOXO protein stability via ubiquitination and proteasome degradationBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2011
- Interleukin-6 Enhances Glucose-Stimulated Insulin Secretion From Pancreatic β-CellsDiabetes, 2011
- Mice with AS160/TBC1D4-Thr649Ala Knockin Mutation Are Glucose Intolerant with Reduced Insulin Sensitivity and Altered GLUT4 TraffickingCell Metabolism, 2011
- MicroRNAs in resolution of acute inflammation: identification of novel resolvin Dl‐miRNA circuitsThe FASEB Journal, 2010
- Hyperglycemia During Total Parenteral NutritionDiabetes Care, 2009
- The Randle cycle revisited: a new head for an old hatAmerican Journal of Physiology-Endocrinology and Metabolism, 2009
- Insulin Signaling in α Cells Modulates Glucagon Secretion In VivoCell Metabolism, 2009
- Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actionsThe Journal of Experimental Medicine, 2008
- Interleukin-6 regulates pancreatic α-cell mass expansionProceedings of the National Academy of Sciences of the United States of America, 2008
- PGC-1 promotes insulin resistance in liver through PPAR-α-dependent induction of TRB-3Nature Medicine, 2004