Psychiatric effect of MCFA via odorant receptor

Abstract

Psychiatric regulations through fatty acid receptors (FFARs) have been extensively studied in a variety of metabolic tissues, including gut and cranial nerve endings. Recent studies on the gut-brain axis support a close relationship between FFAR and the hypothalamic-pituitary-adrenal (HPA) axis, a neuroendocrine system that regulates stress response and mood. However, the expression and functional studies of FFARs in the HPA axis are poorly understood. Here, we present a specific odorant receptor (OR) that is expressed in pituitary gland responding to medium-chain fatty acid (MCFA). The histological location and cell type were also identified by immunohistochemistry, and it was revealed that OR (+) cells were located in the anterior lobe of the pituitary gland, co-localizing with ACTH. The blood ACTH and corticosterone level were measured after intraperitoneal injection of medium-chain fatty acid (MCFA) followed by acute restraint stress. Interestingly, MCFA injection showed an inhibitory effect on both ACTH and corticosterone releases. Furthermore, anxiety and depression behaviors were assessed under chronic restraint stress condition through MCFA treatment, and decreased anxiety and depression behaviors. Finally, the generation of specific OR-KO mice exhibited abnormal HPA axis activity as well as depression- and anxiety-related behaviors. In conclusion, our study has demonstrated the potential role of OR response to stress through the HPA axis, suggesting that OR may be an important therapeutic target for mood disorders