Aerobic glycolysis is important for zebrafish larval wound closure and tail regeneration

The underlying mechanisms of appendage regeneration remain largely unknown and uncovering these mechanisms in capable organisms has far-reaching implications for potential treatments in humans. Recent studies implicate a requirement for metabolic reprogramming reminiscent of the Warburg effect during successful appendage and organ regeneration. As changes are thus predicted to be highly dynamic, methods permitting direct, real-time visualisation of metabolites at the tissue and organismal level would offer a significant advance in defining the influence of metabolism on regeneration and healing. We sought to examine whether glycolytic activity was altered during larval fin regeneration, utilising the genetically encoded biosensor, Laconic, enabling the spatiotemporal assessment of lactate levels in living zebrafish. We present evidence for a rapid increase in lactate levels within min following injury, with a role of aerobic glycolysis in actomyosin contraction and wound closure. We also find a second wave of lactate production, associated with overall larval tail regeneration. Chemical inhibition of glycolysis attenuates both the contraction of the wound and regrowth of tissue following tail amputation, suggesting aerobic glycolysis is necessary at two distinct stages of regeneration.

Automated summary

The mechanisms of appendage regeneration are still largely unknown, and metabolic reprogramming plays an important role in the process. This study used a genetically encoded biosensor called Laconic to evaluate lactate levels during fin regeneration in zebrafish. The findings showed a rapid increase in lactate levels following injury, with a role of aerobic glycolysis in actomyosin contraction and wound closure. Additionally, a second wave of lactate production was observed during larval tail regeneration. Inhibiting glycolysis hindered wound contraction and tissue regrowth, indicating the necessity of aerobic glycolysis at two distinct stages of regeneration.