Regulation and physiological functions of phoenixin

Abstract

Phoenixin is a newly discovered neuropeptide generated from small integral membrane protein 20. Phoenixin is a ligand for the G protein-coupled receptor 173 (GPR173) and has been detected in central and peripheral tissues of human, rats, mice, bovine, and zebrafish. It was initially involved in regulating reproductive function by stimulating the luteinizing hormone release from pituitary cells by increasing the level of gonadotropin-releasing hormone. Recently, many functions of phoenixin have been generalized, including regulation of food intake, memory, Alzheimer's disease, anxiety, inflammation, neuronal and microglial activity, energy metabolism and body fluid balance, cardiovascular function, and endocrine activity. In addition, the interaction between phoenixin and nesfatin-1 have been revealed. The present article summarized the latest research progress on physiological function of phoenixin, suggesting that it is a potential target for novel drug development and clinical application.

Keywords: GPR173; inflammation; nesfatin-1; phoenixin; reproduction.

FIGURE 1

The physiological and pathological roles of phoenixin. AHA, Anterior hypothalamic area; Akt, protein kinase B; AMPK, AMP-activated protein kinase; ATF4, activating transcription factor 4; AVP, arginine vasopressin; cAMP, cyclic adenosine monophosphate; C/EBP, CCAAT/enhancer binding protein; CREB, cAMP-response element binding protein; CRF1/CRF2, corticotropin-releasing factor 1/2; CCK, cholecystokinin; E2, estradiol; eIF-2α, eukaryotic translation initiation factor 2α; eNOS, endothelial nitric oxide synthase; ERK, extracellular signal-related kinase; FSH, follicle-stimulating hormone; FSI, fasting serum insulin; GH, growth hormone; GhRH-R, growth hormone-releasing hormone receptor; GnRH, gonadotropin-releasing hormone; GnRH-R, gonadotropin-releasing hormone receptor; GOAT, ghrelin-O-acyl transferase; HAECs, human aortic endothelial cells; HFD, high-fat diet; HMGB1, high mobility group box1; HO-1, heme oxygenase-1; ICAM-1, intercellular adhesion molecule-1; IL-1β, interleukin-1β; IL-8, interleukin-8; LH, luteinizing hormone; LPS, lipopolysaccharide; MCP-1, monocyte chemotactic protein-1; Myd88, myeloid differentiation primary response 88; NF-κB, nuclear factor-κB; NLRP3, NOD-like receptor protein 3; NOX-4, NADPH oxidase 4; NPY1, neuropeptide Y1; NPY5, neuropeptide Y5; NRF2, Erythroid 2-related factor 2; NST, nucleus of the solitary tract; Oct-1, octamer-binding transcription factor-1; OT, oxytocin; ox-LDL, oxidized low-density lipoprotein; PCOS, polycystic ovary syndrome; PKA, protein kinase A; PGC-1α, peroxisome-proliferator-activated receptor coactivator (PGC)-1α; ROS, reactive oxygen species; SIRT1, Sirtuin1; TLR4, toll-like receptor 4; VCAM-1, vascular cell adhesion molecule-1; VSMCs, vascular smooth muscle cells; Δψm; mitochondrial membrane potential.