Accumulation of Acetaldehyde in aldh2.1-/- Zebrafish Causes Increased Retinal Angiogenesis and Impaired Glucose Homeostasis

In conclusion, the data have identified acetaldehyde as the preferred substrate for Aldh2.1’s detoxification ability. In zebrafish acetaldehyde induces impaired glucose metabolism by blocking gene expression of glucokinase and glucose-6-phosphatase. Moreover, Stress-activated protein Kinases JNK and p38 MAPK were activated by elevated endogenous acetaldehyde leading to increased angiogenesis and vasodilatory effects in aldh2.1-/- zebrafish mutants. Characterization of aldh2.1 knockout zebrafish mutants regarding effects on reactive metabolite detoxification, metabolomics, genomics and organ health - especially vascular health.