Activation of OR1A1 suppresses PPAR-γ expression by inducing HES-1 in cultured hepatocytes

Chunyan Wu, Yaoyao Jia, Ji Hae Lee, Yeonji Kim, Sivakumar Sekharan, Victor S. Batista, Sung Joon Lee

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

Olfactory receptors (ORs) comprise the largest G protein-coupled receptor gene superfamily. Recent studies indicate that ORs are also expressed in non-olfactory organs, including metabolically active tissues, although their biological functions in these tissues are largely unknown. In this study, OR1A1 expression was detected in HepG2 liver cells. OR1A1 activation by (-)-carvone, a known OR1A1 ligand, increased the cyclic adenosine monophosphate (cAMP), but not intracellular Ca2+ concentration, thereby inducing protein kinase A (PKA) activity with subsequent phosphorylation of cAMP response element-binding protein (CREB) and upregulation of the CREB-responsive gene hairy and enhancer of split (HES)-1, a corepressor of peroxisome proliferator-activated receptor-γ (PPAR-γ) in hepatocytes. In (-)-carvone-stimulated cells, the repression of PPAR-γ reduced the expression of the target gene, mitochondrial glycerol-3-phosphate acyltransferase, which encodes a key enzyme involved in triglyceride synthesis. Intracellular triglyceride level and lipid accumulation were reduced in cells stimulated with (-)-carvone, effects that were diminished following the loss of OR1A1 function. These results indicate that OR1A1 may function as a non-redundant receptor in hepatocytes that regulates the PKA-CREB-HES-1 signaling axis and thereby modulates hepatic triglyceride metabolism.

Original languageEnglish
Pages (from-to)75-80
Number of pages6
JournalInternational Journal of Biochemistry and Cell Biology
Volume64
DOIs
Publication statusPublished - 2015 Jul 1

Keywords

  • CREB
  • Lipid metabolism
  • OR1A1
  • Olfactory receptor
  • PKA

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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