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

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.