Regulation of Adipogenesis and Thermogenesis through Mouse Olfactory Receptor 23 Stimulated by α-Cedrene in 3T3-L1 Cells.

Tao Tong,Jinju Park,Taesun Park,Cheil Moon

doi:10.3390/nu10111781

Tao Tong, Jinju Park + Show 2 more

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https://doi.org/10.3390/nu10111781

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Abstract

Olfactory receptors (ORs) are G protein-coupled receptors that perform important physiological functions beyond their role as odorant detectors in the olfactory sensory neurons. In the present study, we describe a novel role for one of these ORs, mouse olfactory receptor 23 (MOR23), as a regulator of adipogenesis and thermogenesis in 3T3-L1 cells. Downregulation of MOR23 by small interfering RNA in 3T3-L1 cells enhanced intracellular lipid accumulation and reduced the oxygen consumption rate. In agreement with this phenotype, MOR23 deletion significantly decreased intracellular cyclic adenosine monophosphate (cAMP) levels and protein amounts of adenylyl cyclase 3 (ADCY3), protein kinase A catalytic subunit (PKA Cα), phospho-5′-adenosine monophosphate (AMP)-activated protein kinase (AMPK), and phospho-cAMP-responsive element-binding protein (CREB), along with upregulation of adipogenic genes and downregulation of genes involved in thermogenesis. Activation of MOR23 by α-cedrene, a novel natural ligand of MOR23, significantly reduced lipid content, increased the oxygen consumption rate, and stimulated reprogramming of the metabolic signature of 3T3-L1 cells, and these changes elicited by α-cedrene were absent in MOR23-deficient cells. These findings point to the role of MOR23 as a regulator of adipogenesis and thermogenesis in adipocytes.

Highlights

G protein-coupled receptors (GPCRs) constitute by far the largest receptor family in mammals and are involved in the regulation of virtually all cellular and physiological functions in the body.Owing to their ability to bind to ligands with high specificity and affinity, GPCRs are preferentially targeted for the development of new therapeutics and account for ~40% of the currently exploited drug targets [1]
To test whether mouse olfactory receptor 23 (MOR23)-mediated signaling pathways are involved in adipogenesis, we knocked down MOR23 in 3T3-L1 cells, using MOR23-specific siRNA
These findings were confirmed by colorimetric quantification of the intracellular triglyceride concentration in 3T3-L1 cells transfected with MOR23 siRNA (Figure 1A)

Summary

Introduction

G protein-coupled receptors (GPCRs) constitute by far the largest receptor family in mammals and are involved in the regulation of virtually all cellular and physiological functions in the body. Owing to their ability to bind to ligands with high specificity and affinity, GPCRs are preferentially targeted for the development of new therapeutics and account for ~40% of the currently exploited drug targets [1]. ORs in the gut [5], spleen [6], liver [7], gastrointestinal tract [8], prostate [9], and testicles [10] appear to play specific signaling roles in the regulation of normal physiology and development These observations make ORs promising markers and potential therapeutic targets in human diseases beyond the usefulness for the fragrance industry

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