Vitamin A Supplementation Induces AMFK Production to Promote Cartilage Proliferation and Antler Growth in Sika Deer

Antlers are unique mammalian organs that grow rapidly through extensive cartilage proliferation. Vitamin A (VA), via retinoic acid, is known to influence skeletal development, yet its contribution to antler growth remains unclear. We investigated whether rumen-protected VA supplementation modulates antler biology in sika deer by integrating gut microbiota profiling, fecal and serum metabolomics, antler cartilage transcriptomics, and in vitro chondrocyte assays. VA was associated with compositional shifts in the gut microbiota and altered metabolic profiles in feces and serum. Notably, the melatonin-derived metabolite AMFK increased in both matrices and showed strong associations with antler weight and cartilage-related gene expression. VA-supplemented deer exhibited higher antler weight, and antler transcriptomes indicated changes in pathways consistent with cartilage extracellular matrix and growth signaling. In chondrocytes, AMFK promoted proliferation and upregulated chondrogenic markers. Together, these findings suggest that VA may promote antler growth through a microbiota–metabolite–gene axis rather than by altering systemic retinol alone.