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Time-restricted feeding promotes muscle function through purine cycle and AMPK signaling in Drosophila obesity models

Author

Listed:
  • Christopher Livelo

    (University of Alabama at Birmingham)

  • Yiming Guo

    (University of Alabama at Birmingham)

  • Farah Abou Daya

    (University of Alabama at Birmingham)

  • Vasanthi Rajasekaran

    (University of Alabama at Birmingham)

  • Shweta Varshney

    (Salk Institute for Biological Studies
    Molecular Biology Institute, San Diego State University)

  • Hiep D. Le

    (Salk Institute for Biological Studies)

  • Stephen Barnes

    (University of Alabama at Birmingham)

  • Satchidananda Panda

    (Salk Institute for Biological Studies)

  • Girish C. Melkani

    (University of Alabama at Birmingham
    Molecular Biology Institute, San Diego State University)

Abstract

Obesity caused by genetic and environmental factors can lead to compromised skeletal muscle function. Time-restricted feeding (TRF) has been shown to prevent muscle function decline from obesogenic challenges; however, its mechanism remains unclear. Here we demonstrate that TRF upregulates genes involved in glycine production (Sardh and CG5955) and utilization (Gnmt), while Dgat2, involved in triglyceride synthesis is downregulated in Drosophila models of diet- and genetic-induced obesity. Muscle-specific knockdown of Gnmt, Sardh, and CG5955 lead to muscle dysfunction, ectopic lipid accumulation, and loss of TRF-mediated benefits, while knockdown of Dgat2 retains muscle function during aging and reduces ectopic lipid accumulation. Further analyses demonstrate that TRF upregulates the purine cycle in a diet-induced obesity model and AMPK signaling-associated pathways in a genetic-induced obesity model. Overall, our data suggest that TRF improves muscle function through modulations of common and distinct pathways under different obesogenic challenges and provides potential targets for obesity treatments.

Suggested Citation

  • Christopher Livelo & Yiming Guo & Farah Abou Daya & Vasanthi Rajasekaran & Shweta Varshney & Hiep D. Le & Stephen Barnes & Satchidananda Panda & Girish C. Melkani, 2023. "Time-restricted feeding promotes muscle function through purine cycle and AMPK signaling in Drosophila obesity models," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36474-4
    DOI: 10.1038/s41467-023-36474-4
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    References listed on IDEAS

    as
    1. Jesús E. Villanueva & Christopher Livelo & Adriana S. Trujillo & Sahaana Chandran & Brendon Woodworth & Leo Andrade & Hiep D. Le & Uri Manor & Satchidananda Panda & Girish C. Melkani, 2019. "Time-restricted feeding restores muscle function in Drosophila models of obesity and circadian-rhythm disruption," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    2. Leonidas S. Lundell & Evelyn B. Parr & Brooke L. Devlin & Lars R. Ingerslev & Ali Altıntaş & Shogo Sato & Paolo Sassone-Corsi & Romain Barrès & Juleen R. Zierath & John A. Hawley, 2020. "Time-restricted feeding alters lipid and amino acid metabolite rhythmicity without perturbing clock gene expression," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    3. Frank Schnorrer & Cornelia Schönbauer & Christoph C. H. Langer & Georg Dietzl & Maria Novatchkova & Katharina Schernhuber & Michaela Fellner & Anna Azaryan & Martin Radolf & Alexander Stark & Krystyna, 2010. "Systematic genetic analysis of muscle morphogenesis and function in Drosophila," Nature, Nature, vol. 464(7286), pages 287-291, March.
    4. Alan L Hutchison & Mark Maienschein-Cline & Andrew H Chiang & S M Ali Tabei & Herman Gudjonson & Neil Bahroos & Ravi Allada & Aaron R Dinner, 2015. "Improved Statistical Methods Enable Greater Sensitivity in Rhythm Detection for Genome-Wide Data," PLOS Computational Biology, Public Library of Science, vol. 11(3), pages 1-29, March.
    5. Fumiaki Obata & Masayuki Miura, 2015. "Enhancing S-adenosyl-methionine catabolism extends Drosophila lifespan," Nature Communications, Nature, vol. 6(1), pages 1-9, November.
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