Phoenixin regulates proliferation and UCP1 expression in rat brown primary preadipocytes

Phoenixin (PNX) is a neuropeptide initially identified for its role in regulating reproductive system functions. Recently, both our research team and others have demonstrated that PNX may contribute to energy homeostasis by stimulating white adipogenesis. However, the role of PNX in regulating brown adipose tissue functions remains unclear. Therefore, this study aimed to evaluate the effects of PNX on the proliferation and differentiation of rat brown preadipocytes isolated from the interscapular fat of male Wistar rats into mature brown adipocytes. Our results show that PNX peptide and its putative receptor, GPR173, are expressed in both undifferentiated and differentiated brown preadipocytes. Furthermore, we found that PNX stimulates the proliferation of rat brown preadipocytes via cAMP/PKA/Epac- and ERK1/2-dependent mechanisms. Additionally, during the differentiation process, PNX upregulated the mRNA expression and protein production of UCP1 and FGF-21, which was accompanied by an increase in PPARγ expression. Conversely, PNX did not affect intracellular lipid accumulation or mitochondrial content during the differentiation of rat brown primary preadipocytes into mature brown fat cells. In conclusion, our results suggest that PNX may be involved in controlling brown adipogenesis.