Research Gut metabolism is reprogrammed to drive exponential growth in Drosophila

Almost all animals pass through a juvenile phase dedicated to growth. Growing organisms have specific needs that may require changes to their metabolism to be met, but these developmental regulations remain poorly understood. Using Drosophila as a model, the Storelli lab has uncovered a striking example of organ-level metabolic reprogramming that fuels growth. Drosophila larvae increase their body mass two hundredfold during their juvenile phase. Most of this growth occurs during the final larval stage, which lasts only a couple of days. The lab now shows that this explosive growth spurt is sustained by reprogramming of intestinal function, with enhanced lipid digestion, metabolism and export. This metabolic switch is triggered by a signaling axis involving steroid hormone and hepatocyte nuclear factor 4, an evolutionarily conserved master regulator of lipid metabolism. The consequences of gut metabolic reprogramming extend beyond growth itself. Even if transient (metabolic reprogramming stops at puberty), it leaves a lasting imprint in adulthood, enhancing fecundity and resilience to environmental stress. Thus, this study contributes to our understanding of how hormonal signals regulate metabolism in specific organs to fulfill developmental demands, and offers new insights into how early-life metabolism shapes lifelong physiology.