IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-59673-7.html
   My bibliography  Save this article

Acute regulation of murine adipose tissue lipolysis and insulin resistance by the TGFβ superfamily protein GDF3

Author

Listed:
  • Nagasuryaprasad Kotikalapudi

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Deepti Ramachandran

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Daniel Vieira

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • William B. Rubio

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Gregory R. Gipson

    (University of Cincinnati College of Medicine)

  • Luca Troncone

    (Massachusetts General Hospital and Harvard Medical School)

  • Kylie Vestal

    (University of Cincinnati College of Medicine)

  • David E. Maridas

    (Harvard School of Dental Medicine)

  • Vicki Rosen

    (Harvard School of Dental Medicine)

  • Paul B. Yu

    (Massachusetts General Hospital and Harvard Medical School)

  • Thomas B. Thompson

    (University of Cincinnati College of Medicine)

  • Alexander S. Banks

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

Abstract

TGFβ superfamily proteins can affect cellular differentiation, thermogenesis, and fibrosis in mammalian adipose tissue. Here we describe a role for Growth Differentiation Factor 3 (GDF3) on mature adipocyte biology. We find inducible GDF3 loss of function in obese adult mice leads to reduced lipolysis, improved glucose tolerance, and reduced glycemic variability. The effects on lipolysis are driven by lower levels of β3-adrenergic receptor, decreased cAMP and PKA signaling. GDF3 is an ALK5, ALK7, ACVR2A and ACVR2B agonist and also a BMPR2 antagonist. Unlike ALK7 or activin E knockouts, acute GDF3 loss of function does not affect body weight or energy balance but significantly improves metabolic health. These results suggest that blocking GDF3 can improve metabolic health independent of body weight and food intake, an intriguing new model for developing anti-diabetic therapies. Together these results provide much-needed clarity to both the molecular pathways involved in GDF3 signaling and its physiological effects.

Suggested Citation

  • Nagasuryaprasad Kotikalapudi & Deepti Ramachandran & Daniel Vieira & William B. Rubio & Gregory R. Gipson & Luca Troncone & Kylie Vestal & David E. Maridas & Vicki Rosen & Paul B. Yu & Thomas B. Thomp, 2025. "Acute regulation of murine adipose tissue lipolysis and insulin resistance by the TGFβ superfamily protein GDF3," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59673-7
    DOI: 10.1038/s41467-025-59673-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-59673-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-59673-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59673-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.