Sex determination gene transformer regulates the male-female difference in Drosophila fat storage via the adipokinetic hormone pathway

  1. Lianna W Wat
  2. Zahid S Chowdhury
  3. Jason W Millington
  4. Puja Biswas
  5. Elizabeth J Rideout  Is a corresponding author
  1. The University of British Columbia, Canada

Abstract

Sex differences in whole-body fat storage exist in many species. For example, Drosophila females store more fat than males. Yet, the mechanisms underlying this sex difference in fat storage remain incompletely understood. Here, we identify a key role for sex determination gene transformer (tra) in regulating the male-female difference in fat storage. Normally, a functional Tra protein is present only in females, where it promotes female sexual development. We show that loss of Tra in females reduced whole-body fat storage, whereas gain of Tra in males augmented fat storage. Tra's role in promoting fat storage was largely due to its function in neurons, specifically the Adipokinetic hormone (Akh)-producing cells (APCs). Our analysis of Akh pathway regulation revealed a male bias in APC activity and Akh pathway function, where this sex-biased regulation influenced the sex difference in fat storage by limiting triglyceride accumulation in males. Importantly, Tra loss in females increased Akh pathway activity, and genetically manipulating the Akh pathway rescued Tra-dependent effects on fat storage. This identifies sex-specific regulation of Akh as one mechanism underlying the male-female difference in whole-body triglyceride levels, and provides important insight into the conserved mechanisms underlying sexual dimorphism in whole-body fat storage.

Data availability

Details of all statistical tests and p-values are in Supplementary file 1. All raw data generated in this study are in Supplementary file 2. All primer sequences are in Supplementary file 3. Fly food media recipe is in Supplementary file 4. Original image files for all images in this study are in their respective Source Data files.

Article and author information

Author details

  1. Lianna W Wat

    The University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6998-0594
  2. Zahid S Chowdhury

    The University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Jason W Millington

    The University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4330-2431
  4. Puja Biswas

    The University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Elizabeth J Rideout

    The University of British Columbia, Vancouver, Canada
    For correspondence
    elizabeth.rideout@ubc.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0012-2828

Funding

Canadian Institutes for Health Research (PJT-153072)

  • Elizabeth J Rideout

CIHR Sex and GenderScience chaor program (GS4-171365)

  • Elizabeth J Rideout

Natural Sciences and Engineering Research Council of Canada (RGPIN-2016-04249)

  • Elizabeth J Rideout

Michael Smith Foundation for Health Research (16876)

  • Elizabeth J Rideout

Canadian Foundation for Innovation (JELF-34879)

  • Elizabeth J Rideout

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Jiwon Shim, Hanyang University, Republic of Korea

Publication history

  1. Received: July 20, 2021
  2. Accepted: October 7, 2021
  3. Accepted Manuscript published: October 21, 2021 (version 1)
  4. Version of Record published: November 16, 2021 (version 2)

Copyright

© 2021, Wat 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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  1. Lianna W Wat
  2. Zahid S Chowdhury
  3. Jason W Millington
  4. Puja Biswas
  5. Elizabeth J Rideout
(2021)
Sex determination gene transformer regulates the male-female difference in Drosophila fat storage via the adipokinetic hormone pathway
eLife 10:e72350.
https://doi.org/10.7554/eLife.72350

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