Heart regeneration potential varies considerably between species, but also within species. While Astyanax mexicanus surface fish regenerate their heart after injury, their Pachón cave-dwelling counterparts cannot and form a permanent fibrotic scar, similar to the human heart. This difference in cardiac regeneration capacity within the same species allows to directly compare the cellular and molecular differences between scarring versus regeneration. Surface fish and Pachón have been exposed to extreme differences in the availability of light and food between the river and caves, and these factors have influenced their metabolism during evolution. Nutrient levels within the cave are significantly lower and as such, the cavefish have become more resistant to starvation and have an increased appetite through a mutation in the melanocortin of the leptin/melanocortin pathway. The cavefish have also developed fatty livers and the total triglyceride content in cavefish is much higher compared to surface fish. We are now looking into how these evolutionary changes in metabolism affect the ability for heart regeneration, which will help to define the ideal metabolic fingerprint facilitating successful regeneration.