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

Animal StudyPreliminary evidence
The takeaway

First-ever characterization of the CART neuropeptide in a reptilian brain reveals its wide distribution and regulation by NPY via Y1 receptors, demonstrating that this energy-balance peptide system is conserved across all vertebrate groups.

>93% peptide similarity

Gecko CART neuropeptide is remarkably conserved compared to rat and human versions, spanning ~350 million years of evolution

What the researchers found

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.

Why it matters

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 numbers in context

The gecko CART cDNA was 683 base pairs. CART-containing neurons were found across multiple brain regions.

How the study worked

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.

Who was studied

Hemidactylus leschenaultii geckos

What this study cannot tell us

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.

How to read the evidence

Preliminary evidence from a single comparative neuroscience study. Well-executed methodology for molecular characterization and neural mapping, but limited to one species.

When this study was published

Published in 2024. Fills a gap in our understanding of neuropeptide conservation across vertebrate evolution.

The bigger picture

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.

Questions still open

  • Why is the ventral arcuate CART population resistant to NPY regulation while dorsal arcuate CART is sensitive?
  • Does manipulating CART levels in reptiles produce the same appetite changes seen in mammals?
  • Could the remarkable conservation of CART peptide sequence suggest pharmaceutical approaches effective across species?

Common questions

What is CART and what does it do?
CART (cocaine- and amphetamine-regulated transcript) is a neuropeptide in the brain that suppresses appetite. It works in opposition to NPY, which stimulates appetite. Together, they form a key regulatory system for energy balance and body weight.
Why study a gecko to understand human appetite control?
By showing that the CART-NPY appetite control system is conserved even in reptiles — a group that diverged from mammals over 300 million years ago — this study demonstrates that this mechanism is truly fundamental to vertebrate biology, making it a robust therapeutic target.

Read the original research

Cocaine- and Amphetamine-Regulated Transcript Peptide in the Central Nervous System of the Gecko, Hemidactylus leschenaultii: Molecular Characterization, Neuroanatomical Organization, and Regulation by Neuropeptide Y.

The Journal of comparative neurology, 532(10), e25672

Citation

Singh, Omprakash; Basu, Sumela; Srivastava, Abhinav; Pradhan, Dipti R; Dandapat, Pallabi; Bathrachalam, Chandramohan; Singru, Praful S. (2024). Cocaine- and Amphetamine-Regulated Transcript Peptide in the Central Nervous System of the Gecko, Hemidactylus leschenaultii: Molecular Characterization, Neuroanatomical Organization, and Regulation by Neuropeptide Y.. The Journal of comparative neurology, 532(10), e25672. https://doi.org/10.1002/cne.25672