Choice of Lipid Emulsion Determines Inflammation of the Gut‐Liver Axis, Incretin Profile, and Insulin Signaling in a Murine Model of Total Parenteral Nutrition. Issue 5 (13th August 2020)

• Record Type: Journal Article
• Authors: Lou, Phing‐How; Lucchinetti, Eliana; Wawrzyniak, Paulina; Morsy, Yasser; Wawrzyniak, Marcin; Scharl, Michael; Krämer, Stefanie D.; Rogler, Gerhard; Hersberger, Martin; Zaugg, Michael
• Other Names: Rogler Gerhard guestEditor.; Zaugg Michael guestEditor.
• Is Part Of: Molecular nutrition & food research. Volume 65:Issue 5(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-08-13
• Subjects: insulin -- liver -- n‐3 fatty acids -- n‐6 fatty acids -- total parenteral nutrition; Food -- Biotechnology -- Periodicals; Food -- Microbiology -- Periodicals; Nutrition -- Periodicals; Food -- Toxicology -- Periodicals; Nutrition -- Periodicals; Food Microbiology -- Periodicals; Food Technology -- Periodicals; Molecular Biology -- Periodicals; 664.0705
• DOI: 10.1002/mnfr.202000412
• Languages: English
• ISSNs: 1613-4125

Abstract

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 : During total parenteral nutrition (TPN), endotoxin from the bowel reaches the liver and stimulates interleukin‐6 (IL‐6) production. IL‐6 enhances insulin release from the pancreas, leading to insulin resistance in liver and skeletal muscle. Omegaven promotes insulin sensitivity by reducing (1) liver IL‐6 production and (2) release of glucagon like peptide‐1 (GLP‐1) and glucose‐dependent insulinotropic peptide (GIP) from the bowel.