A systemic role of macrophage-derived BMP2/4 homolog Dpp in regulating sterol hormone synthesis under dietary stress

A high-sugar diet (HSD), prevalent in Western countries, compromises the growth and development of children and primes their bodies for chronic diseases. Macrophages, which are immune cells found throughout the body, can sense environmental changes and influence surrounding tissues. Using Drosophila as a model, here we show that macrophages respond to an HSD by increasing the production of Decapentaplegic (Dpp), a protein related to human BMP2/4. Dpp then signals to the endocrine system, the prothoracic gland, to inhibit the synthesis of ecdysone, a crucial steroid hormone that triggers the transition from larva to pupa. By reducing ecdysone synthesis, the larval stage is prolonged. This extended developmental period provides larvae exposed to an HSD more time to reach an optimal size. Our findings highlight how different organs communicate to counteract the negative impact of an HSD during development and expand our understanding of Dpp function, showing that it acts not only as a local developmental signal but also as a systemic regulator.