| The Effect of Diet on the Response of Low Density Lipoprotein Receptor Knockout Mice to the Liver X Receptor Agonist T1317. | |
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MedLine Citation:
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PMID: 21558881 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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It has been previously observed that low density lipoprotein receptor knockout (LDLR-/-) mice fed a Western-type diet without cholate and given the liver X receptor (LXR) agonist T1317 develop a persistent and enhanced hypertriglyceridemia. In contrast, LDLR-/- mice fed a Paigen diet with cholate exhibit only a transient increase in plasma triglycerides when given T1317. Cholate as an activator of farnesoid X receptor (FXR) may attenuate T1317-induced triglyceridemia. To determine if cholate was responsible for this transient nature of the hypertriglyceridemia, we orally administered T1317 to LDLR-/- mice fed a modified Paigen diet without cholate. T1317 transiently elevated plasma triglycerides by increasing plasma VLDL. Cholesterol and triglyceride levels in plasma VLDL in T1317-treated mice decreased from peak levels to levels found in vehicle treated mice after 8 weeks of treatment. A gradual decline of hepatic cholesterol and a transient increase in hepatic triglycerides were also observed in T1317-treated mice. T1317 only transiently activated the expression of genes related to liver de novo lipogenesis, while genes related to lipid metabolism were induced in T1317-treated mice including a gradual increase in plasma lipoprotein lipase activity. Atheroprotective effects of T1317 were observed in the innominate artery and aortic arch but not in the aortic sinus. This work indicates that some component(s) in the Paigen diet other than cholate affect the T1317-induced gene expression profile and ameliorate its effects on lipid synthesis that lead to hypertriglyceridemia and fatty liver. These findings are important for LXR-related pharmaceutical development for the treatment of cardiovascular disease. |
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Authors:
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Lu Peng; Richard Hiipakka; Jing-Tian Xie; John Kokontis; Shutsung Liao; Dacheng Peng |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-5-06 |
Journal Detail:
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Title: Journal of cardiovascular pharmacology Volume: - ISSN: 1533-4023 ISO Abbreviation: - Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-5-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7902492 Medline TA: J Cardiovasc Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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* Section of Cardiology, Internal Medicine, JiShuiTan Hospital, Beijing, P. R. China; and † Ben May Department for Cancer Research, University of Chicago, Chicago, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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