Scope: It is aimed to determine the role of mouse olfactory receptor 23 (MOR23) in regulation of glucose uptake in myotubes and adipocytes and investigate whether administration of a possible MOR23 ligand, α-cedrene, attenuates the high fat diet (HFD)-induced glucose intolerance by enhancing the OR-mediated signaling pathway in mice. Methods and Results: MOR23 is genetically inactivated by specific small interfering RNA in C2C12 myotubes and 3T3-L1 adipocytes and stimulated with α-cedrene under both basal and insulin-stimulated conditions. In addition, Male C57BL/6N mice are fed a normal diet, HFD, or HFD supplemented with 0.2% α-cedrene. In C2C12 myotubes and 3T3-L1 adipocytes, genetic inactivation of MOR23 significantly decrease glucose uptake and MOR23 downstream signaling under both basal and insulin-stimulated conditions. On the other hand, α-cedrene-mediated MOR23 stimulation results in increased glucose uptake and upregulation of MOR23 signaling molecules, absent in MOR23-depleted myotubes and adipocytes. Moreover, in mice, α-cedrene administration ameliorates HFD-induced glucose intolerance. Activation of MOR23 signaling cascade is also confirmed in basal and insulin stimulated skeletal muscles and adipose tissues of α-cedrene-treated mice. Conclusions: These findings suggest that MOR23 is a novel factor for the regulation of glucose uptake and whole-body glucose homeostasis and has therapeutic potential for diabetes treatment.
Bibliographical noteFunding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2019R1A2C2003340) and the grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI17C2243).
All Science Journal Classification (ASJC) codes
- Food Science