SIRT1 accelerates the progression of activity-based anorexia

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number2814
JournalNature Communications
Volume11
Issue number1
DOIs
Publication statusPublished - Dec 1 2020

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Robinette, T. M., Nicholatos, J. W., Francisco, A. B., Brooks, K. E., Diao, R. Y., Sorbi, S., Ricca, V., Nacmias, B., Brieño-Enríquez, M. A., & Libert, S. (2020). SIRT1 accelerates the progression of activity-based anorexia. Nature Communications, 11(1), [2814]. https://doi.org/10.1038/s41467-020-16348-9