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A Novel Mechanism for Decreasing Plasma Lipid Level from Imidazoline I-1 Receptor Activation in High Fat Diet-fed Mice.
MedLine Citation:
PMID:  21484668     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The imidazoline I-1 receptor (I-1 R) agonists are widely used to lower blood pressure, but their effects on hyperlipidemia are still obscure. The present study is aimed to evaluate the possible mechanism(s) of I-1 R in the regulation of lipid homeostasis. Farnesoid X receptor (FXR) plays an important role in blood lipid homeostasis; however, the role of FXR in rilmenidine-induced blood lipid lowering action is still unknown. Thus, we administered rilmenidine, a selective agonist of I-1 R, into high fat diet-fed (HFD) mice showing hypertriglyceridemia and hypercholesterolemia. Rilmenidine significantly ameliorated hyperlipidemia in HFD mice after 7 days of administration. Pretreatment with efaroxan, at a dose sufficient to inhibit I-1 R activation, blocked the effects of rilmenidine. Also, in cultured HepG2 cells, rilmenidine dose-dependently induced the expression of farnesoid X receptor (FXR). The rilmenidine-induced FXR expression and FXR-related genes were blocked by efaroxan. However, rilmenidine treatment did not affect the expression of enzymes related to β-oxidation. In conclusion, activation of I-1 R may activate FXR to lower plasma lipids, suggesting I-1 R as a new target for the treatment of hyperlipidemia.
Authors:
C-S Niu; H-T Wu; K-C Cheng; K-C Lin; C-T Chen; J-T Cheng
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-11
Journal Detail:
Title:  Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme     Volume:  -     ISSN:  1439-4286     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-4-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0177722     Medline TA:  Horm Metab Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© Georg Thieme Verlag KG Stuttgart · New York.
Affiliation:
Department of Nursing, Tzu Chi College of Technology, Hualien City, Taiwan.
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