Tumour-driven lipid accumulation in oenocytes reflects systemic lipid alterations
- Author(s)
- Liu, C; Golenkina, S; Fahey, N; Kumar, P; Cheng, LY;
- Details
- Publication Year 2026-05-07,Volume 22,Issue #5,Page e1012150
- Journal Title
- PLoS Genetics
- Publication Type
- Research article
- Abstract
- Cancer cachexia is a multifactorial syndrome characterized by systemic metabolic dysfunction, including liver steatosis. In this study, we examined the role of larval oenocytes - hepatocyte-like cells, in a Drosophila model of cancer cachexia. We found that oenocytes in tumour-bearing larvae accumulate lipid droplets in response to tumour-secreted signals, Gbb and ImpL2. This lipid accumulation reflects systemic changes in lipid metabolism, responding to lipid metabolism manipulations in either the fat body or the muscle. Disrupting lipid synthesis/breakdown (via FASN1 and Bmm), storage (via Lsd2), or trafficking (via apolipoproteins) in these tissues significantly modulated lipid droplet accumulation in oenocytes. Moreover, oenocyte-specific knockdown of FASN1 reduced their lipid content and non-autonomously affected lipid droplet size in the fat body, suggesting cross-regulatory interactions between these tissues. Cachectic oenocytes also exhibited altered signaling profiles, characterized by reduced PI3K signalling. Enhancing PI3K signalling through Akt overexpression restored oenocyte size and reduced lipid levels; however, these changes did not significantly improve muscle integrity. Together, our data suggests that dynamic exchange of lipids occur between the fat body, oenocytes and the muscle during cancer cachexia. While the fat body and muscle lipid pools are key regulators of muscle integrity, oenocytes - despite their metabolic responsiveness, do not appear to play an active role in preserving muscle function during cachexia.
- Publisher
- PLOS
- Department(s)
- Laboratory Research
- Publisher's Version
- https://doi.org/10.1371/journal.pgen.1012150
- Open Access at Publisher's Site
https://doi.org/10.1371/journal.pgen.1012150- Terms of Use/Rights Notice
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Creation Date: 2026-05-19 02:35:05
Last Modified: 2026-05-19 02:35:24