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

44 Citations (Scopus)


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
Publication statusPublished - 2015 Jul 1

Bibliographical note

Funding Information:
The authors thank Dr. Hiro Matsunami for discussions regarding the surface expression of OR1A1, and Dr. Koo Jaehyung (DGIST, Korea) for insights on OR research. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. NRF-2013R1A2A2A01016176 ).

Publisher Copyright:
© 2015 Elsevier Ltd.


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

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology


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