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

9 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

Fingerprint

rilmenidine
Imidazolines
High Fat Diet
Nutrition
Chemical activation
Fats
efaroxan
Lipids
Plasmas
Hyperlipidemias
Homeostasis
Blood
Hypertriglyceridemia
Blood pressure
Hep G2 Cells
imidazoline I1 receptors
Hypercholesterolemia
Cultured Cells
Genes

Keywords

  • cholesterol
  • efaroxan
  • imidazoline receptor
  • rilmenidine
  • triglyceride

ASJC Scopus subject areas

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

Cite this

A novel mechanism for decreasing plasma lipid level from imidazoline I-1 receptor activation in high fat diet-fed mice. / Niu, C. S.; Wu, H. T.; Cheng, K. C.; Lin, K. C.; Chen, C. T.; Cheng, J. T.

In: Hormone and Metabolic Research, Vol. 43, No. 7, 13.04.2011, p. 458-463.

Research output: Contribution to journalArticle

Niu, C. S. ; Wu, H. T. ; Cheng, K. C. ; Lin, K. C. ; Chen, C. T. ; Cheng, J. T. / A novel mechanism for decreasing plasma lipid level from imidazoline I-1 receptor activation in high fat diet-fed mice. In: Hormone and Metabolic Research. 2011 ; Vol. 43, No. 7. pp. 458-463.
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