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 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.

Procyanidins from hawthorn (Crataegus pinnatifida) alleviate lipid metabolism disorder via inhibiting insulin resistance and oxidative stress, normalizing the gut microbiota structure and intestinal barrier, and further suppressing hepatic inflammation and lipid accumulation

“…In particular, a chronic high-fat diet dramatically lowered the tight junction proteins occludin and claudin-1, while synergistically aggravating the impairment of the intestinal barrier and LPS accumulation. 58 Moreover, enormous studies indicated that the supplementation of nutrients protects the intestinal tight junction proteins against impairment, such as anthocyanins from the fruits of Lycium ruthenicum Murray. 59 We found that the intervention of HPC significantly decreased gut-derived endotoxin transfer and recovered the integrity of the intestinal barrier, which contributed to inhibiting the inflammatory response caused by intestinal leakage.…”

Quantitative profiling of inflammatory and pro-resolving lipid mediators in human adolescents and mouse plasma using UHPLC-MS/MS

“…Mouse experiments were performed as in Lou et al [21] and were approved by the University of Alberta Animal Policy and Welfare Committee (AUP00002007). Briefly, male C57BL/6mice aged 20 weeks and instrumented with a tunneled jugular vein catheter were purchased from Charles River Laboratories (Wilmington, MA, USA).…”

Liver complications of total parenteral nutrition: the latest therapeutic strategies

“…Parenteral nutrition may cause insulin resistance and hyperglycemia, due to the intravenous administration of concentrated glucose [11,12,13]. In addition, in patients with short bowel syndrome, the production of incretins (a group of intestinal hormones that increase postprandial insulin secretion by pancreatic β cells) is reduced [8].…”

“…This may be due to the fact that the clearance of fish oil-based lipid emulsions is less dependent on LPL activity and shows favorable uptake by peripheral tissue. Studies show that n-3 PUFA counteract the negative effects of saturated fatty acids on insulin sensitivity, inflammation, and immunosuppression [13].…”