Epidermal tyrosine catabolism is critical for metabolic homeostasis and survival against high-protein diets in Drosophila

The insect epidermis that forms the exoskeleton and determines the body size of an organism has the potential to respond and adapt to the changing nutritional environment. However, the extent to which the tissue contributes to adaptation to varying dietary protein availability, as well as its role as a metabolic regulator, remains incompletely understood. Here, we show that the Drosophila epidermis promptly reacts to dietary protein intake, promoting tyrosine (Tyr) catabolism. Among the enzymes involved in Tyr degradation, 4- hydroxyphenylpyruvate dioxygenase (Hpd) is particularly induced under high-protein regimens. We found that AMP-activated protein kinase (AMPK) pathway and forkhead box O subfamily (FoxO) induce Hpd expression. Impaired Hpd function in the epidermis leads to aberrant increases in internal Tyr levels and its metabolites, disrupting larval development under high-protein diets. Taken together, our findings uncover the critical role of epidermal metabolism in adapting to imbalanced protein environments and hence in promoting animal survival. Summary statementTyrosine degradation is upregulated in Drosophila epidermal tissue via the AMPK-FoxO axis upon dietary high-protein stress.