title: A novel mechanism for decreasing plasma lipid level from imidazoline I-1 receptor activation in high fat diet-fed mice.
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.
authors.affiliation: Department of Nursing, Tzu Chi College of Technology, Hualien City, Taiwan, ROC.
authors.forename: C-S
authors.initials: CS
authors.lastname: Niu
authors.forename: H-T
authors.initials: HT
authors.lastname: Wu
authors.forename: K-C
authors.initials: KC
authors.lastname: Cheng
authors.forename: K-C
authors.initials: KC
authors.lastname: Lin
authors.forename: C-T
authors.initials: CT
authors.lastname: Chen
authors.forename: J-T
authors.initials: JT
authors.lastname: Cheng
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology*; D005247:Feeding Behavior / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood; D054755:Imidazoline Receptors; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008055:Lipids / Q000097:blood*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010080:Oxazoles / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D000077769:Rilmenidine; D015398:Signal Transduction / Q000187:drug effects; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D004041:Dietary Fats; D054755:Imidazoline Receptors; D047908:Intracellular Signaling Peptides and Proteins; D008055:Lipids; D010080:Oxazoles; D018160:Receptors, Cytoplasmic and Nuclear; D000077769:Rilmenidine; D000099150:Receptor, Farnesoid X-Activated; C503041:Nisch protein, mouse