The CART Neuropeptide System Is Conserved Across All Vertebrates, Including Reptiles, and Interacts with NPY for Energy Balance

CART neuropeptide was characterized for the first time in a reptilian brain (gecko), showing >93% similarity to mammalian CART peptides and regulation by NPY via Y1 receptors in the hypothalamic arcuate nucleus.

Cloned gecko CART cDNA (683 bp). Mapped CART-containing neurons using immunohistochemistry. Used double immunofluorescence to show NPY innervation of CART neurons. Ex vivo hypothalamic slice treatment with NPY and Y1 agonist to test regulation of CART expression.

Understanding that CART-NPY interactions controlling energy balance are conserved across all vertebrate groups — from fish to reptiles to mammals — strengthens the evidence that this is a fundamental biological mechanism. This evolutionary perspective can inform therapeutic targeting of appetite-regulating peptide systems.

The CART and NPY peptide systems are key players in appetite regulation and energy homeostasis. Showing that their interaction is conserved in reptiles — completing the picture across all major vertebrate groups — underscores the fundamental importance of these neuropeptide pathways and validates their relevance as therapeutic targets.

Single species (gecko) studied. Ex vivo hypothalamic slice experiments may not fully replicate in vivo conditions. The functional consequences of NPY-mediated CART suppression on feeding behavior in geckos were not directly measured. The ventral arcuate CART population was unaffected by NPY, and this differential regulation needs explanation.