Methylglyoxal-derived hydroimidazolone, MG-H1, increases food intake by altering tyramine signaling via the GATA transcription factor ELT-3 in Caenorhabditis elegans

  1. Muniesh Muthaiyan Shanmugam
  2. Jyotiska Chaudhuri
  3. Durai Sellegounder
  4. Amit Kumar Sahu
  5. Sanjib Guha
  6. Manish Chamoli
  7. Brian Hodge
  8. Neelanjan Bose
  9. Charis Amber
  10. Dominique O Farrera
  11. Gordon Lithgow
  12. Richmond Sarpong
  13. James Galligan
  14. Pankaj Kapahi  Is a corresponding author
  1. Buck Institute for Research on Aging, United States
  2. University of California, Berkeley, United States
  3. University of Arizona, United States

Abstract

The Maillard reaction, a chemical reaction between amino acids and sugars, is exploited to produce flavorful food ubiquitously, from the baking industry to our everyday lives. However, the Maillard reaction also occurs in all cells, from prokaryotes to eukaryotes, forming Advanced Glycation End-products (AGEs). AGEs are a heterogeneous group of compounds resulting from the irreversible reaction between biomolecules and α-dicarbonyls (α-DCs), including methylglyoxal (MGO), an unavoidable byproduct of anaerobic glycolysis and lipid peroxidation. We previously demonstrated that Caenorhabditis elegans mutants lacking the glod-4 glyoxalase enzyme displayed enhanced accumulation of α-DCs, reduced lifespan, increased neuronal damage, and touch hypersensitivity. Here, we demonstrate that glod-4 mutation increased food intake and identify that MGO-derived hydroimidazolone, MG-H1, is a mediator of the observed increase in food intake. RNAseq analysis in glod-4 knockdown worms identified upregulation of several neurotransmitters and feeding genes. Suppressor screening of the overfeeding phenotype identified the tdc-1-tyramine-tyra-2/ser-2 signaling as an essential pathway mediating AGEs (MG-H1) induced feeding in glod-4 mutants. We also identified the elt-3 GATA transcription factor as an essential upstream regulator for increased feeding upon accumulation of AGEs by partially controlling the expression of tdc-1 gene. Further, the lack of either tdc-1 or tyra-2/ser-2 receptors suppresses the reduced lifespan and rescues neuronal damage observed in glod-4 mutants. Thus, in C. elegans, we identified an elt-3 regulated tyramine-dependent pathway mediating the toxic effects of MG-H1 AGE. Understanding this signaling pathway may help understand hedonistic overfeeding behavior observed due to modern AGEs-rich diets.

Data availability

All data generated during this study are included in the manuscript. The RNAseq data is included as supplementary file.

Article and author information

Author details

  1. Muniesh Muthaiyan Shanmugam

    Buck Institute for Research on Aging, Novato, United States
    Competing interests
    No competing interests declared.
  2. Jyotiska Chaudhuri

    Buck Institute for Research on Aging, Novato, United States
    Competing interests
    No competing interests declared.
  3. Durai Sellegounder

    Buck Institute for Research on Aging, Novato, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0776-0307
  4. Amit Kumar Sahu

    Buck Institute for Research on Aging, Novato, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0063-5447
  5. Sanjib Guha

    Buck Institute for Research on Aging, Novato, United States
    Competing interests
    No competing interests declared.
  6. Manish Chamoli

    Buck Institute for Research on Aging, Novato, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0339-7894
  7. Brian Hodge

    Buck Institute for Research on Aging, Novato, United States
    Competing interests
    No competing interests declared.
  8. Neelanjan Bose

    Buck Institute for Research on Aging, Novato, United States
    Competing interests
    No competing interests declared.
  9. Charis Amber

    Department of Chemistry, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
  10. Dominique O Farrera

    Department of Pharmacology and Toxicology, University of Arizona, Tucson, United States
    Competing interests
    No competing interests declared.
  11. Gordon Lithgow

    Buck Institute for Research on Aging, Novato, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8953-3043
  12. Richmond Sarpong

    Department of Chemistry, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
  13. James Galligan

    Department of Pharmacology and Toxicology, University of Arizona, Tucson, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5612-0680
  14. Pankaj Kapahi

    Buck Institute for Research on Aging, Novato, United States
    For correspondence
    Pkapahi@buckinstitute.org
    Competing interests
    Pankaj Kapahi, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5629-4947

Funding

National Institutes of Health (R01AG061165)

  • Pankaj Kapahi

National Institutes of Health (R01AG068288)

  • Pankaj Kapahi

Larry L. Hillblom Foundation (2021-A-007-FEL)

  • Pankaj Kapahi

National Institutes of Health (R01DK133196)

  • James Galligan

National Institutes of Health (R35GM137910)

  • James Galligan

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

Reviewing Editor

  1. Scott F Leiser, University of Michigan, United States

Version history

  1. Received: August 4, 2022
  2. Preprint posted: August 19, 2022 (view preprint)
  3. Accepted: September 19, 2023
  4. Accepted Manuscript published: September 20, 2023 (version 1)
  5. Accepted Manuscript updated: September 22, 2023 (version 2)
  6. Version of Record published: October 27, 2023 (version 3)

Copyright

© 2023, Muthaiyan Shanmugam 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. Muniesh Muthaiyan Shanmugam
  2. Jyotiska Chaudhuri
  3. Durai Sellegounder
  4. Amit Kumar Sahu
  5. Sanjib Guha
  6. Manish Chamoli
  7. Brian Hodge
  8. Neelanjan Bose
  9. Charis Amber
  10. Dominique O Farrera
  11. Gordon Lithgow
  12. Richmond Sarpong
  13. James Galligan
  14. Pankaj Kapahi
(2023)
Methylglyoxal-derived hydroimidazolone, MG-H1, increases food intake by altering tyramine signaling via the GATA transcription factor ELT-3 in Caenorhabditis elegans
eLife 12:e82446.
https://doi.org/10.7554/eLife.82446

Share this article

https://doi.org/10.7554/eLife.82446

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