Rilmenidine improves hepatic steatosis through p38-dependent pathway to higher the expression of farnesoid X receptor

Po Sheng Yang, Hung Tsung Wu, Hsien Hui Chung, Chun Ta Chen, Chin Wen Chi, Ching Hua Yeh, Juei Tang Cheng

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The nuclear receptor farnesoid X receptor (FXR) regulates pathways in lipid, glucose, and energy metabolism. Activation of FXR in mice significantly improved high-fat diet-induced hepatic steatosis. It has been reported that activation of imidazoline I-1 receptor by rilmenidine increases the expression of FXR in human hepatoma cell line, Hep G2 cell, to regulate the target genes relating to lipid metabolism; activation of FXR by rilmenidine exerts an antihyperlipidemic action. However, signals for this action of rilmenidine are still unknown. In the present study, hepatic steatosis induced in mice by high-fat diet was improved by rilmenidine after intraperitoneal injection at 1 mg/kg daily for 12 weeks. Also, mediation of I-1 receptors was identified using the specific antagonist efaroxan. Moreover, rilmenidine decreased the oleic acid-induced lipid accumulation in Hep G2 cells. Otherwise, rilmenidine increased the phosphorylation of p38 to increase the expression of FXR. Deletion of calcium ions by BAPTA-AM reversed the rilmenidine-induced p38 phosphorylation. In conclusion, we suggest that rilmenidine activates I-1 receptor to increase intracellular calcium ions that may enhance the phosphorylation of p38 to higher the expression of FXR for improvement of hepatic steatosis in both animals and cells.

Original languageEnglish
Pages (from-to)51-56
Number of pages6
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume385
Issue number1
DOIs
Publication statusPublished - Jan 1 2012
Externally publishedYes

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Keywords

  • Farnesoid X receptor
  • Hepatic steatosis
  • Imidazoline I-1 receptor
  • p38
  • Rilmenidine

ASJC Scopus subject areas

  • Pharmacology

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