Olfactory receptor 10J5 responding to α-cedrene regulates hepatic steatosis via the cAMP-PKA pathway

Tao Tong, Sang Eun Ryu, Yeojin Min, Claire A. De March, Caroline Bushdid, Jérôme Golebiowski, Cheil Moon, Taesun Park

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

Ectopic expression and functions of odorant receptors (ORs) in the human body have aroused much interest in the past decade. Mouse olfactory receptor 23 (MOR23, olfr16) and its human orthologue, OR10J5, have been found to be functionally expressed in several non-olfactory systems. Here, using MOR23- and OR10J5-expressing Hana3A cells, we identified α-cedrene, a natural compound that protects against hepatic steatosis in mice fed the high-fat diet, as a novel agonist of these receptors. In human hepatocytes, an RNA interference-mediated knockdown of OR10J5 increased intracellular lipid accumulation, along with upregulation of lipogenic genes and downregulation of genes related to fatty acid oxidation. α-Cedrene stimulation resulted in a significant reduction in lipid contents of human hepatocytes and reprogramming of metabolic signatures, which are mediated by OR10J5, as demonstrated by receptor knockdown experiments using RNA interference. Taken together, our findings show a crucial role of OR10J5 in the regulation of lipid accumulation in human hepatocytes.

Original languageEnglish
Article number9471
JournalScientific reports
Volume7
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea Grant funded by the Korea Government (NRF-2016R1A2B4016189), and SRC program (Center for Food & Nutritional Genomics: Grant no. 2015R1A5A6001906) of the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology.

Publisher Copyright:
© 2017 The Author(s).

All Science Journal Classification (ASJC) codes

  • General

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