2. Academic Validation
  3. Olfactory receptor 10J5 responding to α-cedrene regulates hepatic steatosis via the cAMP-PKA pathway

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

  • Sci Rep. 2017 Aug 25;7(1):9471. doi: 10.1038/s41598-017-10379-x.
Tao Tong 1,  Sang Eun Ryu 2,  Yeojin Min 1,  Claire A de March 3 4,  Caroline Bushdid 3,  Jérôme Golebiowski 2 3,  Cheil Moon 2 5,  Taesun Park 6
Affiliations

Affiliations

  • 1 Department of Food and Nutrition, Brain Korea 21 PLUS Project, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-749, South Korea.
  • 2 Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Daegu, 711-873, South Korea.
  • 3 Institut de Chimie de Nice, Université Nice Sophia Antipolis, Nice cedex 02, France.
  • 4 Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, 27710, United States.
  • 5 Convergence Research Advanced Centre for Olfaction, Daegu Gyeongbuk Institute of Science and Technology, Daegu, 711-873, South Korea.
  • 6 Department of Food and Nutrition, Brain Korea 21 PLUS Project, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-749, South Korea. tspark@yonsei.ac.kr.
PMID: 28842679 DOI: 10.1038/s41598-017-10379-x
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.

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