Department of Food and Nutrition, Brain Korea 21 PLUS Project, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea.
Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Daegu 711-873, Korea.
Nutrients. 2018 Nov 16;10(11):1781. doi: 10.3390/nu10111781.
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.
嗅觉受体（ORs）是 G 蛋白偶联受体，除了在嗅觉感觉神经元中作为气味探测器发挥重要的生理功能外。在本研究中，我们描述了其中一种 OR，即小鼠嗅觉受体 23（MOR23），作为 3T3-L1 细胞中脂肪生成和生热作用的调节剂的新作用。用小干扰 RNA 下调 3T3-L1 细胞中的 MOR23 增强了细胞内脂质积累并降低了耗氧量。与这种表型一致，MOR23 缺失显著降低了细胞内环磷酸腺苷（cAMP）水平和腺苷酸环化酶 3（ADCY3）、蛋白激酶 A 催化亚基（PKA Cα）、磷酸-5'-腺嘌呤核苷酸（AMP）-激活蛋白激酶（AMPK）和磷酸-cAMP 反应元件结合蛋白（CREB）的蛋白量，同时上调了脂肪生成基因并下调了参与生热作用的基因。α-cedrene（MOR23 的新型天然配体）激活 MOR23 可显著降低脂质含量，增加耗氧量，并刺激 3T3-L1 细胞代谢特征的重新编程，而这些由 α-cedrene 引起的变化在 MOR23 缺失细胞中不存在。这些发现表明 MOR23 在脂肪细胞中作为脂肪生成和生热作用的调节剂的作用。
