The fat body cortical actin network regulates Drosophila inter-organ nutrient trafficking, signaling, and adipose cell size
- The University of Texas Southwestern Medical Center, United States
- University of Texas Southwestern Medical Center, United States
Abstract
Defective nutrient storage and adipocyte enlargement (hypertrophy) are emerging features of metabolic syndrome and type 2 diabetes. Within adipose tissues, how the cytoskeletal network contributes to adipose cell size, nutrient uptake, fat storage, and signaling remain poorly understood. Utilizing the Drosophila larval fat body (FB) as a model adipose tissue, we show that a specific actin isoform-Act5C-forms the cortical actin network necessary to expand adipocyte cell size for biomass storage in development. Additionally, we uncover a non-canonical role for the cortical actin cytoskeleton in inter-organ lipid trafficking. We find Act5C localizes to the FB cell surface and cell-cell boundaries, where it intimately contacts peripheral LDs (pLDs), forming a cortical actin network for cell architectural support. FB-specific loss of Act5C perturbs FB triglyceride (TG) storage and LD morphology, resulting in developmentally delayed larvae that fail to develop into flies. Utilizing temporal RNAi-depletion approaches, we reveal that Act5C is indispensable post-embryogenesis during larval feeding as FB cells expand and store fat. Act5C-deficient FBs fail to grow, leading to lipodystrophic larvae unable to accrue sufficient biomass for complete metamorphosis. In line with this, Act5C-deficient larvae display blunted insulin signaling and reduced feeding. Mechanistically, we also show this diminished signaling correlates with decreased lipophorin (Lpp) lipoprotein-mediated lipid trafficking, and find Act5C is required for Lpp secretion from the FB for lipid transport. Collectively, we propose that the Act5C-dependent cortical actin network of Drosophila adipose tissue is required for adipose tissue size-expansion and organismal energy homeostasis in development, and plays an essential role in inter-organ nutrient transport and signaling.
Data availability
We have now provided raw datasets for the manuscript on a Dryad file site (doi:10.5061/dryad.4mw6m90d4).
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Data from: The fat body cortical actin network regulates Drosophila inter-organ nutrient trafficking, signaling, and adipocyte cell sizeDryad Digital Repository, doi:10.5061/dryad.4mw6m90d4.
Article and author information
Author details
Funding
NIDDK (DK126887)
- Rupali Ugrankar-Banerjee
- Son Tran
- Jade Bowerman
- Anastasiia Kovalenko
- Blessy Paul
- W Mike Henne
NIGMS (GM119768)
- W Mike Henne
Welch Foundation (I-1873)
- W Mike Henne
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Hugo J Bellen, Baylor College of Medicine, United States
Version history
- Preprint posted: June 16, 2022 (view preprint)
- Received: June 17, 2022
- Accepted: April 25, 2023
- Accepted Manuscript published: May 5, 2023 (version 1)
- Version of Record published: May 22, 2023 (version 2)
Copyright
© 2023, Ugrankar-Banerjee et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The fat body cortical actin network regulates Drosophila inter-organ nutrient trafficking, signaling, and adipose cell size
eLife 12:e81170.
https://doi.org/10.7554/eLife.81170
Further reading
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