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

Taskinen, M.‐R. et al. (2021) Effects of liraglutide on the metabolism of triglyceride‐rich lipoproteins in type 2 diabetes. Diabetes, Obesity and Metabolism, 23(5), pp. 1191-1201. (doi: 10.1111/dom.14328) (PMID:33502078)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Packard, Professor Chris
• Authors: Taskinen, M.‐R., Björnson, E., Matikainen, N., Söderlund, S., Pietiläinen, K. H., Ainola, M., Hakkarainen, A., Lundbom, N., Fuchs, J., Thorsell, A., Andersson, L., Adiels, M., Packard, C. J., and Borén, J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Diabetes, Obesity and Metabolism
• Publisher: Wiley
• ISSN: 1462-8902
• ISSN (Online): 1463-1326
• Published Online: 27 January 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Diabetes, Obesity and Metabolism 23(5): 1191-1201
• Publisher Policy: Reproduced under a Creative Commons License