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

Horm Metab Res. 2011 Jun;43(7):458-63. doi: 10.1055/s-0031-1275325. Epub 2011 Apr 11.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dietary Fats / administration & dosage
  • Dietary Fats / pharmacology*
  • Feeding Behavior / drug effects*
  • Gene Expression Regulation / drug effects
  • Hep G2 Cells
  • Humans
  • Hyperlipidemias / blood
  • Imidazoline Receptors
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lipids / blood*
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxazoles / pharmacology
  • Oxidation-Reduction / drug effects
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Rilmenidine
  • Signal Transduction / drug effects


  • Dietary Fats
  • Imidazoline Receptors
  • Intracellular Signaling Peptides and Proteins
  • Lipids
  • Nisch protein, mouse
  • Oxazoles
  • Receptors, Cytoplasmic and Nuclear
  • farnesoid X-activated receptor
  • Rilmenidine