Endothelin-1 promotes cytoplasmic accumulation of RIP140 through a ET A-PLCβ-PKCε pathway

Ping Chih Ho, Yao Chen Tsui, Yi Wei Lin, Shawna D. Persaud, Li Na Wei*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

7 Scopus citations


The physiological signal activating cytoplasmic accumulation of nuclear receptor interacting protein 140 (RIP140) in adipocytes was unclear. We uncover that endothelin-1 (ET-1) promotes cytoplasmic accumulation of RIP140 in 3T3-L1 adipocytes. We determine ET-1's signal transduction pathway in adipocytes, which is by activating ET A receptor-PLCβ-nuclear PKCε. Blocking this pathway in 3T3-L1 adipocyte cultures, by treating cells with an ET A antagonist, inhibiting PLCβ, or silencing PKCε, reduces ET-1-stimulated cytoplasmic accumulation of RIP140. In a HFD-fed obese mouse model, administration of a selective ET A antagonist, ambrisentan, effectively dampens cytoplasmic accumulation of RIP140 in the epididymal adipose tissue and reduces HFD-caused adipocyte dysfunctions. Importantly, ambrisentan improves blood glucose control and reduces the severity of hepatic steatosis in HFD-fed mice. This study reports a physiological signal that stimulates nuclear export of RIP140 in adipocytes and provides evidence for a strategy using selective ET A antagonist to treat obesity-induced insulin resistance and, possibly, other metabolic disorders.

Original languageEnglish
Pages (from-to)176-183
Number of pages8
JournalMolecular and Cellular Endocrinology
Issue number2
StatePublished - 04 04 2012
Externally publishedYes


  • Ambrisentan
  • Cytoplasm
  • ET receptor
  • Endothelin-1
  • Insulin sensitivity
  • RIP140


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