Negative regulation of adiponectin secretion by receptor interacting protein 140 (RIP140)

Ping Chih Ho, Li Na Wei*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

19 Scopus citations

Abstract

RIP140 (receptor-interacting protein 140) is highly expressed in mature adipocytes and functions as a co-repressor for gene expression involved in lipid and glucose metabolism. In adipocytes, activated PKCε (Protein kinase C epsilon) phosphorylates nuclear RIP140 which is then subsequently arginine methylated and exported to the cytoplasm. In the cytoplasm, RI140 can elicit additional activities. Here we report a new functional role for cytoplasmic RIP140 in adipocyte in regulating adiponectin secretion. Targeting cytoplasmic RIP140 by knocking down RIP140 itself or its nuclear export trigger, PKCε, promotes the secretion of adiponectin without affecting the production or oligomerization of adiponectin. Consequentially, conditioned media from either RIP140- or PKCε-silenced adipocytes, which contain higher levels of adiponectin, enhance glucose uptake in C2C12 cells and reduce gluconeogenesis in HepG2 cells. Further, these effects can be inhibited by an adiponectin-neutralizing antibody. The effect of cytoplasmic RIP140 in regulating adiponectin secretion is via interacting with AS160, a known RIP140-interacting protein. This study reveals a new functional role for cytoplasmic RIP140 in modulating adiponectin vesicle secretion, and suggests that targeting cytoplasmic RIP140 may be a potentially effective therapeutic strategy to improve adiponectin secretion and possibly to manage metabolic disorders.

Original languageEnglish
Pages (from-to)71-76
Number of pages6
JournalCellular Signalling
Volume24
Issue number1
DOIs
StatePublished - 01 2012
Externally publishedYes

Keywords

  • Adiponectin
  • Cytoplasmic
  • Gluconeogenesis
  • Glucose uptake
  • Insulin sensitivity
  • RIP140

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