Effects of liraglutide on the metabolism of triglyceride-rich lipoproteins in type 2 diabetes

Marja Riitta Taskinen, Elias Björnson, Niina Matikainen, Sanni Söderlund, Kirsi H. Pietiläinen, Mari Ainola, Antti Hakkarainen, Nina Lundbom, Johannes Fuchs, Annika Thorsell, Linda Andersson, Martin Adiels, Chris J. Packard, Jan Borén*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

1 Citation (Scopus)

Abstract

Aim: To elucidate the impact of liraglutide on the kinetics of apolipoprotein (apo)B48- and apoB100-containing triglyceride-rich lipoproteins in subjects with type 2 diabetes (T2D) after a single fat-rich meal. Materials and Methods: Subjects with T2D were included in a study to investigate postprandial apoB48 and apoB100 metabolism before and after 16 weeks on l.8 mg/day liraglutide (n = 14) or placebo (n = 4). Stable isotope tracer and compartmental modelling techniques were used to determine the impact of liraglutide on chylomicron and very low-density lipoprotein (VLDL) production and clearance after a single fat-rich meal. Results: Liraglutide reduced apoB48 synthesis in chylomicrons by 60% (p <.0001) and increased the triglyceride/apoB48 ratio (i.e. the size) of chylomicrons (p <.001). Direct clearance of chylomicrons, a quantitatively significant pathway pretreatment, decreased by 90% on liraglutide (p <.001). Liraglutide also reduced VLDL1-triglyceride secretion (p =.017) in parallel with reduced liver fat. Chylomicron-apoB48 production and particle size were related to insulin sensitivity (p =.015 and p <.001, respectively), but these associations were perturbed by liraglutide. Conclusions: In a physiologically relevant setting that mirrored regular feeding in subjects with T2D, liraglutide promoted potentially beneficial changes on postprandial apoB48 metabolism. Using our data in an integrated metabolic model, we describe how the action of liraglutide in T2D on chylomicron and VLDL kinetics could lead to decreased generation of remnant lipoproteins.

Original languageEnglish
JournalDiabetes, Obesity and Metabolism
DOIs
Publication statusE-pub ahead of print - 2021
MoE publication typeA1 Journal article-refereed

Keywords

  • dyslipidaemia
  • GLP-1 analogue
  • type 2 diabetes

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