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


Lou, Phing-How; Lucchinetti, Eliana; Wawrzyniak, Paulina; Morsy, Yasser; Wawrzyniak, Marcin; Scharl, Michael; Krämer, Stefanie D; Rogler, Gerhard; Hersberger, Martin; Zaugg, Michael (2020). Choice of Lipid Emulsion Determines Inflammation of the Gut-Liver Axis, Incretin Profile, and Insulin Signaling in a Murine Model of Total Parenteral Nutrition. Molecular Nutrition & Food Research:Epub ahead of print.

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-γ, while OV-TPN reduces interleukin-4, monocyte chemoattractant protein-1, and interleukin-1α. 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.

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-γ, while OV-TPN reduces interleukin-4, monocyte chemoattractant protein-1, and interleukin-1α. 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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
04 Faculty of Medicine > University Hospital Zurich > Clinic for Gastroenterology and Hepatology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Life Sciences > Biotechnology
Life Sciences > Food Science
Language:German
Date:30 July 2020
Deposited On:27 Aug 2020 09:03
Last Modified:28 Aug 2020 20:00
Publisher:Wiley-VCH Verlag
ISSN:1613-4125
OA Status:Closed
Publisher DOI:https://doi.org/10.1002/mnfr.202000412
PubMed ID:32729969
Project Information:
  • : FunderSNSF
  • : Grant IDCRSII5_177225
  • : Project TitleNovel lipid nano-emulsions with superior biological actions: shifting paradigms in current parenteral nutrition

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