Title
GLP-1 Receptor Activation Inhibits VLDL Production and Reverses Hepatic Steatosis by Decreasing Hepatic Lipogenesis in High-Fat-Fed APOE*3-Leiden Mice
Author
Parlevliet, E.T.
Wang, Y.
Geerling, J.J.
Schröder-Van der Elst, J.P.
Picha, K.
O'Neil, K.
Stojanovic-Susulic, V.
Ort, T.
Havekes, L.M.
Romijn, J.A.
Pijl, H.
Rensen, P.C.N.
Publication year
2012
Abstract
Objective: In addition to improve glucose intolerance, recent studies suggest that glucagon-like peptide-1 (GLP-1) receptor agonism also decreases triglyceride (TG) levels. The aim of this study was to evaluate the effect of GLP-1 receptor agonism on very-low-density lipoprotein (VLDL)-TG production and liver TG metabolism. Experimental Approach: The GLP-1 peptide analogues CNTO3649 and exendin-4 were continuously administered subcutaneously to high fat diet-fed APOE*3-Leiden transgenic mice. After 4 weeks, hepatic VLDL production, lipid content, and expression profiles of selected genes involved in lipid metabolism were determined. Results: CNTO3649 and exendin-4 reduced fasting plasma glucose (up to -30% and -28% respectively) and insulin (-43% and -65% respectively). In addition, these agents reduced VLDL-TG production (-36% and -54% respectively) and VLDL-apoB production (-36% and -43% respectively), indicating reduced production of VLDL particles rather than reduced lipidation of apoB. Moreover, they markedly decreased hepatic content of TG (-39% and -55% respectively), cholesterol (-30% and -55% respectively), and phospholipids (-23% and -36% respectively), accompanied by down-regulation of expression of genes involved in hepatic lipogenesis (Srebp-1c, Fasn, Dgat1) and apoB synthesis (Apob). Conclusion: GLP-1 receptor agonism reduces VLDL production and hepatic steatosis in addition to an improvement of glycemic control. These data suggest that GLP-receptor agonists could reduce hepatic steatosis and ameliorate dyslipidemia in patients with type 2 diabetes mellitus. © 2012 Parlevliet et al.
Subject
EELS - Earth, Environmental and Life Sciences
Life
Healthy Living
Biomedical Innovation
Biology
MHR - Metabolic Health Research
To reference this document use:
http://resolver.tudelft.nl/uuid:b1a9cb78-916f-4961-810a-babece89cb7c
DOI
https://doi.org/10.1371/journal.pone.0049152
TNO identifier
465815
ISSN
1932-6203
Source
PLoS ONE, 7 (7)
Document type
article