A novel mechanism for decreasing plasma lipid level from imidazoline I-1 receptor activation in high fat diet-fed mice

C. S. Niu, H. T. Wu, K. C. Cheng, K. C. Lin, C. T. Chen, J. T. Cheng

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)458-463
Number of pages6
JournalHormone and Metabolic Research
Volume43
Issue number7
DOIs
Publication statusPublished - Apr 13 2011
Externally publishedYes

Keywords

  • cholesterol
  • efaroxan
  • imidazoline receptor
  • rilmenidine
  • triglyceride

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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