Macrophage metabolic reprogramming during dietary stress influences adult body size in Drosophila
Immune cells are increasingly recognized as nutrient sensors; however, their developmental role in regulating growth under homeostasis or dietary stress remains elusive. Here, we show that Drosophila larval macrophages, in response to excessive dietary sugar (HSD), reprogram their metabolic state by activating glycolysis, thereby enhancing TCA-cycle flux, and increasing lipogenesis-while concurrently maintaining a lipolytic state. Although this immune-metabolic configuration correlates with growth retardation under HSD, our genetic analyses reveal that enhanced lipogenesis supports growth, whereas glycolysis and lipolysis are growth-inhibitory. Notably, promoting immune-driven lipogenesis offsets early growth inhibition in imaginal discs caused by glycolytic and lipolytic immune-metabolic states. Our findings reveal a model of immune-metabolic imbalance, where growth-suppressive states (glycolysis, lipolysis) dominate over a growth-supportive lipogenic state, thereby impairing early organ size control and ultimately affecting adult size. Overall, this study provides important insights into dietary stress-induced immune-metabolic reprogramming and its link to organ size regulation and early developmental plasticity.
Authors
- Manisha Goyal (ORCID: https://orcid.org/0000-0002-0899-8288)
- Nivedita Hariharan (ORCID: https://orcid.org/0000-0001-5468-0580)
- Sajad Ahmad Najar (ORCID: https://orcid.org/0000-0002-7934-9795)
- Syed Rizvi (ORCID: https://orcid.org/0000-0002-6150-6801)
- Anusree Mahanta (ORCID: https://orcid.org/0000-0003-0352-0645)
- Subramanian Ramaswamy (ORCID: https://orcid.org/0000-0002-6709-190X)
- Dasaradhi Palakodeti (ORCID: https://orcid.org/0000-0003-2219-4785)
- Angela Giangrande (ORCID: https://orcid.org/0000-0001-6278-5120)
- Tina Mukherjee (ORCID: https://orcid.org/0000-0003-3776-5536)
- Ajit Bhowmick
- Preethi Parupalli
Institutions
- The University of Texas at Dallas (US)
- University of Dallas (US)
- Purdue University West Lafayette (US)
- University of Trans-Disciplinary Health Sciences and Technology (IN)
- Institute for Stem Cell Biology and Regenerative Medicine (IN)
- Institut de Biologie Moléculaire et Cellulaire (FR)
- University of North Texas at Dallas (US)
- SASTRA University (IN)
Publication Details
- Journal
- EMBO Reports
- Published
- 2025-09-09
- DOI
- https://doi.org/10.1038/s44319-025-00574-7
- Citations
- 3
- Primary Topic
- Invertebrate Immune Response Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 2.39
Funders
- Purdue University
- Wellcome Trust
- Children's Investment Fund Foundation
- Department of Biotechnology, Ministry of Science and Technology, India
- Department of Science and Technology, Ministry of Science and Technology, India
- Centre National de la Recherche Scientifique
- The Wellcome Trust DBT India Alliance
- Directorate for Biological Sciences
- Science and Engineering Research Board
- National Centre for Biological Sciences