Apolipoprotein-AI mimetic peptides D-4F and L-5F decrease hepatic inflammation and increase insulin sensitivity in C57BL/6 mice.

Autor: Kristine C McGrath, Xiaohong Li, Stephen M Twigg, Alison K Heather
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: PLoS ONE, Vol 15, Iss 1, p e0226931 (2020)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0226931
Popis: BACKGROUND:Apolipoprotein-AI (apo-AI) is the major apolipoprotein found in high density lipoprotein particles (HDLs). We previously demonstrated that apo-AI injected directly into high-fat diet fed mice improved insulin sensitivity associated with decreased hepatic inflammation. While our data provides compelling proof of concept, apoA-I mimetic peptides are more clinically feasible. The aim of this study was to test whether apo-AI mimetic peptide (D-4F and L-5F) treatment will emulate the effects of full-length apo-AI to improve insulin sensitivity. METHODS:Male C57BL/6 mice were fed a high-fat diet for 16 weeks before receiving D4F mimetic peptide administered via drinking water or L5F mimetic peptide administered by intraperitoneal injection bi-weekly for a total of five weeks. Glucose tolerance and insulin tolerance tests were conducted to assess the effects of the peptides on insulin resistance. Effects of the peptides on inflammation, gluconeogenic enzymes and lipid synthesis were assessed by real-time PCR of key markers involved in the respective pathways. RESULTS:Treatment with apo-AI mimetic peptides D-4F and L-5F showed: (i) improved blood glucose clearance (D-4F 1.40-fold AUC decrease compared to HFD, P
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