Discovery of a transdermally deliverable pentapeptide for activating AdipoR1 to promote hair growth

Alopecia induced by aging or side effects of medications affects millions of people worldwide and impairs the quality of life; however, there is a limit to the current medications. Here, we identify a small transdermally deliverable 5‐mer peptide (GLYYF; P5) that activates adiponectin receptor 1 (AdipoR1) and promotes hair growth. P5 sufficiently reproduces the biological effect of adiponectin protein via AMPK signaling pathway, increasing the expression of hair growth factors in the dermal papilla cells of human hair follicle. P5 accelerates hair growth ex vivo and induces anagen hair cycle in mice in vivo. Furthermore, we elucidate a key spot for the binding between AdipoR1 and adiponectin protein using docking simulation and mutagenesis studies. This study suggests that P5 could be used as a topical peptide drug for alleviating pathological conditions, which can be improved by adiponectin protein, such as alopecia.