Olfactory Receptor 10J5 Responding to α-cedrene Regulates Hepatic Steatosis Via the CAMP-PKA Pathway

Overview

Journal Sci Rep

Specialty Science

Date 2017 Aug 27

PMID 28842679

Citations 22

Authors

Tao Tong

Sang Eun Ryu

Yeojin Min

Claire A de March

Caroline Bushdid

Jerome Golebiowski

Cheil Moon

Taesun Park

Affiliations

Soon will be listed here.

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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