The fat body cortical actin network regulates Drosophila inter-organ nutrient trafficking, signaling, and adipose cell size

  1. Rupali Ugrankar-Banerjee
  2. Son Tran
  3. Jade Bowerman
  4. Anastasiia Kovalenko
  5. Blessy Paul
  6. W Mike Henne  Is a corresponding author
  1. The University of Texas Southwestern Medical Center, United States
  2. 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).

The following data sets were generated

Article and author information

Author details

  1. Rupali Ugrankar-Banerjee

    Ugrankar-Banerjee, The University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Son Tran

    Department of Cell Biology, The University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Jade Bowerman

    Department of Cell Biology, The University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Anastasiia Kovalenko

    Department of Cell Biology, The University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Blessy Paul

    Department of Cell Biology, The University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. W Mike Henne

    Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, United States
    For correspondence
    mike.henne@utsouthwestern.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2135-2799

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.

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.

Metrics

  • 2,716
    views
  • 349
    downloads
  • 12
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Rupali Ugrankar-Banerjee
  2. Son Tran
  3. Jade Bowerman
  4. Anastasiia Kovalenko
  5. Blessy Paul
  6. W Mike Henne
(2023)
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

Share this article

https://doi.org/10.7554/eLife.81170

Further reading

    1. Cell Biology
    2. Genetics and Genomics
    Keva Li, Nicholas Tolman ... UK Biobank Eye and Vision Consortium
    Research Article

    A glaucoma polygenic risk score (PRS) can effectively identify disease risk, but some individuals with high PRS do not develop glaucoma. Factors contributing to this resilience remain unclear. Using 4,658 glaucoma cases and 113,040 controls in a cross-sectional study of the UK Biobank, we investigated whether plasma metabolites enhanced glaucoma prediction and if a metabolomic signature of resilience in high-genetic-risk individuals existed. Logistic regression models incorporating 168 NMR-based metabolites into PRS-based glaucoma assessments were developed, with multiple comparison corrections applied. While metabolites weakly predicted glaucoma (Area Under the Curve = 0.579), they offered marginal prediction improvement in PRS-only-based models (p=0.004). We identified a metabolomic signature associated with resilience in the top glaucoma PRS decile, with elevated glycolysis-related metabolites—lactate (p=8.8E-12), pyruvate (p=1.9E-10), and citrate (p=0.02)—linked to reduced glaucoma prevalence. These metabolites combined significantly modified the PRS-glaucoma relationship (Pinteraction = 0.011). Higher total resilience metabolite levels within the highest PRS quartile corresponded to lower glaucoma prevalence (Odds Ratiohighest vs. lowest total resilience metabolite quartile=0.71, 95% Confidence Interval = 0.64–0.80). As pyruvate is a foundational metabolite linking glycolysis to tricarboxylic acid cycle metabolism and ATP generation, we pursued experimental validation for this putative resilience biomarker in a human-relevant Mus musculus glaucoma model. Dietary pyruvate mitigated elevated intraocular pressure (p=0.002) and optic nerve damage (p<0.0003) in Lmx1bV265D mice. These findings highlight the protective role of pyruvate-related metabolism against glaucoma and suggest potential avenues for therapeutic intervention.

    1. Cell Biology
    2. Immunology and Inflammation
    Alejandro Rosell, Agata Adelajda Krygowska ... Esther Castellano Sanchez
    Research Article

    Macrophages are crucial in the body’s inflammatory response, with tightly regulated functions for optimal immune system performance. Our study reveals that the RAS–p110α signalling pathway, known for its involvement in various biological processes and tumourigenesis, regulates two vital aspects of the inflammatory response in macrophages: the initial monocyte movement and later-stage lysosomal function. Disrupting this pathway, either in a mouse model or through drug intervention, hampers the inflammatory response, leading to delayed resolution and the development of more severe acute inflammatory reactions in live models. This discovery uncovers a previously unknown role of the p110α isoform in immune regulation within macrophages, offering insight into the complex mechanisms governing their function during inflammation and opening new avenues for modulating inflammatory responses.