Impaired Arginine Metabolism in Hair Follicles: A Potential Mechanism in Androgenetic Alopecia

Abstract Androgenetic alopecia (AGA) is a prevalent hair loss disorder characterized by an unclear pathogenesis mechanism and limited therapeutic efficacy. Despite a growing body of evidence indicating a link between AGA and metabolic disorders, the precise role of metabolism in AGA development remains elusive. In this study, we employed targeted metabolome profiling to identify distinct metabolic signatures in AGA patients, with a particular focus on amino acid-related metabolic pathways. Notably, our findings highlight a significant decrease in serum abundance of arginine in AGA patients.Locally, impaired arginine metabolism in hair follicles (HFs) experiencing balding was assumed, as evidenced by the heightened expression of ARG1, the pivotal enzyme regulating the arginine-ornithine transition, and the diminished expression of the arginine transporter SLC7A1. Our study further demonstrated that arginine deficiency hinders human hair growth by antagonizing the mTOR signaling pathway. Moreover, the administration of arginine effectively safeguards against the inhibition of hair growth induced by DHT in an AGA-like mouse model and in balding HFs obtained from AGA patients.Collectively, these findings reveal that obstruction of anagen maintenance cause by arginine deficiency occurs in AGA patients and raise the possibility of supplementation with arginine as a promising clinical treatment strategy.