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SIRT1 accelerates the progression of activity-based anorexia

Author

Listed:
  • Timothy M. Robinette

    (University of Pittsburgh School of Medicine
    Cornell University)

  • Justin W. Nicholatos

    (Cornell University)

  • Adam B. Francisco

    (Cornell University)

  • Kayla E. Brooks

    (Cornell University)

  • Rachel Y. Diao

    (Cornell University)

  • Sandro Sorbi

    (University of Florence
    IRCCS Fondazione Don Carlo Gnocchi)

  • Valdo Ricca

    (University of Florence
    University of Florence)

  • Benedetta Nacmias

    (University of Florence)

  • Miguel A. Brieño-Enríquez

    (University of Pittsburgh School of Medicine)

  • Sergiy Libert

    (Cornell University
    Calico Life Sciences)

Abstract

Food consumption is fundamental for life, and eating disorders often result in devastating or life-threatening conditions. Anorexia nervosa (AN) is characterized by a persistent restriction of energy intake, leading to lowered body weight, constant fear of gaining weight, and psychological disturbances of body perception. Herein, we demonstrate that SIRT1 inhibition, both genetically and pharmacologically, delays the onset and progression of AN behaviors in activity-based anorexia (ABA) models, while SIRT1 activation accelerates ABA phenotypes. Mechanistically, we suggest that SIRT1 promotes progression of ABA, in part through its interaction with NRF1, leading to suppression of a NMDA receptor subunit Grin2A. Our results suggest that AN may arise from pathological positive feedback loops: voluntary food restriction activates SIRT1, promoting anxiety, hyperactivity, and addiction to starvation, exacerbating the dieting and exercising, thus further activating SIRT1. We propose SIRT1 inhibition can break this cycle and provide a potential therapy for individuals suffering from AN.

Suggested Citation

  • Timothy M. Robinette & Justin W. Nicholatos & Adam B. Francisco & Kayla E. Brooks & Rachel Y. Diao & Sandro Sorbi & Valdo Ricca & Benedetta Nacmias & Miguel A. Brieño-Enríquez & Sergiy Libert, 2020. "SIRT1 accelerates the progression of activity-based anorexia," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16348-9
    DOI: 10.1038/s41467-020-16348-9
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