IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-07684-y.html
   My bibliography  Save this article

A phenotypic Caenorhabditis elegans screen identifies a selective suppressor of antipsychotic-induced hyperphagia

Author

Listed:
  • Anabel Perez-Gomez

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Maria Carretero

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Natalie Weber

    (University of California, San Diego)

  • Veronika Peterka

    (University of California, San Diego)

  • Alan To

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Viktoriya Titova

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Gregory Solis

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Olivia Osborn

    (University of California, San Diego)

  • Michael Petrascheck

    (The Scripps Research Institute
    The Scripps Research Institute)

Abstract

Antipsychotic (AP) drugs are used to treat psychiatric disorders but are associated with significant weight gain and metabolic disease. Increased food intake (hyperphagia) appears to be a driving force by which APs induce weight gain but the mechanisms are poorly understood. Here we report that administration of APs to C. elegans induces hyperphagia by a mechanism that is genetically distinct from basal food intake. We exploit this finding to screen for adjuvant drugs that suppress AP-induced hyperphagia in C. elegans and mice. In mice AP-induced hyperphagia is associated with a unique hypothalamic gene expression signature that is abrogated by adjuvant drug treatment. Genetic analysis of this signature using C. elegans identifies two transcription factors, nhr-25/Nr5a2 and nfyb-1/NFYB to be required for AP-induced hyperphagia. Our study reveals that AP-induced hyperphagia can be selectively suppressed without affecting basal food intake allowing for novel drug discovery strategies to combat AP-induced metabolic side effects.

Suggested Citation

  • Anabel Perez-Gomez & Maria Carretero & Natalie Weber & Veronika Peterka & Alan To & Viktoriya Titova & Gregory Solis & Olivia Osborn & Michael Petrascheck, 2018. "A phenotypic Caenorhabditis elegans screen identifies a selective suppressor of antipsychotic-induced hyperphagia," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07684-y
    DOI: 10.1038/s41467-018-07684-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-07684-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-07684-y?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Rizaldy C. Zapata & Maria Carretero & Felipe Castellani Gomes Reis & Besma S. Chaudry & Jachelle Ofrecio & Dinghong Zhang & Roman Sasik & Theodore Ciaraldi & Michael Petrascheck & Olivia Osborn, 2022. "Adipocytes control food intake and weight regain via Vacuolar-type H+ ATPase," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

    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:9:y:2018:i:1:d:10.1038_s41467-018-07684-y. 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.