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Publication : SIRT1 accelerates the progression of activity-based anorexia.

First Author  Robinette TM Year  2020
Journal  Nat Commun Volume  11
Issue  1 Pages  2814
PubMed ID  32499508 Mgi Jnum  J:294117
Mgi Id  MGI:6448039 Doi  10.1038/s41467-020-16348-9
Citation  Robinette TM, et al. (2020) SIRT1 accelerates the progression of activity-based anorexia. Nat Commun 11(1):2814
abstractText  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.
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