GLP-1 receptor activation inhibits VLDL production and reverses hepatic steatosis by decreasing hepatic lipogenesis in high-fat-fed APOE*3-Leiden mice.
<h4>Objective</h4>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 (...
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2012
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oai:doaj.org-article:22f65b1129434deb817148c89ddabf952021-11-18T08:10:08ZGLP-1 receptor activation inhibits VLDL production and reverses hepatic steatosis by decreasing hepatic lipogenesis in high-fat-fed APOE*3-Leiden mice.1932-620310.1371/journal.pone.0049152https://doaj.org/article/22f65b1129434deb817148c89ddabf952012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23133675/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Objective</h4>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.<h4>Experimental approach</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>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.Edwin T ParlevlietYanan WangJanine J GeerlingJanny P Schröder-Van der ElstKristen PichaKaryn O'NeilVedrana Stojanovic-SusulicTatiana OrtLouis M HavekesJohannes A RomijnHanno PijlPatrick C N RensenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e49152 (2012) |
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Medicine R Science Q |
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Medicine R Science Q Edwin T Parlevliet Yanan Wang Janine J Geerling Janny P Schröder-Van der Elst Kristen Picha Karyn O'Neil Vedrana Stojanovic-Susulic Tatiana Ort Louis M Havekes Johannes A Romijn Hanno Pijl Patrick C N Rensen GLP-1 receptor activation inhibits VLDL production and reverses hepatic steatosis by decreasing hepatic lipogenesis in high-fat-fed APOE*3-Leiden mice. |
| description |
<h4>Objective</h4>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.<h4>Experimental approach</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>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. |
| format |
article |
| author |
Edwin T Parlevliet Yanan Wang Janine J Geerling Janny P Schröder-Van der Elst Kristen Picha Karyn O'Neil Vedrana Stojanovic-Susulic Tatiana Ort Louis M Havekes Johannes A Romijn Hanno Pijl Patrick C N Rensen |
| author_facet |
Edwin T Parlevliet Yanan Wang Janine J Geerling Janny P Schröder-Van der Elst Kristen Picha Karyn O'Neil Vedrana Stojanovic-Susulic Tatiana Ort Louis M Havekes Johannes A Romijn Hanno Pijl Patrick C N Rensen |
| author_sort |
Edwin T Parlevliet |
| title |
GLP-1 receptor activation inhibits VLDL production and reverses hepatic steatosis by decreasing hepatic lipogenesis in high-fat-fed APOE*3-Leiden mice. |
| title_short |
GLP-1 receptor activation inhibits VLDL production and reverses hepatic steatosis by decreasing hepatic lipogenesis in high-fat-fed APOE*3-Leiden mice. |
| title_full |
GLP-1 receptor activation inhibits VLDL production and reverses hepatic steatosis by decreasing hepatic lipogenesis in high-fat-fed APOE*3-Leiden mice. |
| title_fullStr |
GLP-1 receptor activation inhibits VLDL production and reverses hepatic steatosis by decreasing hepatic lipogenesis in high-fat-fed APOE*3-Leiden mice. |
| title_full_unstemmed |
GLP-1 receptor activation inhibits VLDL production and reverses hepatic steatosis by decreasing hepatic lipogenesis in high-fat-fed APOE*3-Leiden mice. |
| title_sort |
glp-1 receptor activation inhibits vldl production and reverses hepatic steatosis by decreasing hepatic lipogenesis in high-fat-fed apoe*3-leiden mice. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/22f65b1129434deb817148c89ddabf95 |
| work_keys_str_mv |
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| _version_ |
1718422093757939712 |