Adapted physical activity, a therapeutic tool in anorexia nervosa? – ANAKYN

Adapted Physical activity (APA) is a new putative therapeutic tool in anorexia nervosa (AN) but randomized clinical trial are still lacking, such as mechanistic studies. In activity-based anorexia mice (ABA), we previously reported that maintained physical activity during refeeding is associated with restored anxiety-like behavior, higher fat-free mass and improved metabolic response. The metabolism of Tryptophan (TRP)-kynurenin (KYN) may contribute to these effects. KYN, produced from TRP, can be metabolized into neuroprotective kynurenic acid or to neurotoxic quinolinic acid. Interestingly, ABA mice exhibit tissue alterations of TRP-KYN metabolism and beneficial effects of APA could be related to an increased muscle KYN conversion into kynurenic acid. However, deepen investigations are needed to confirm this hypothesis and to evaluate the effects of APA during refeeding in AN patients. In the ANAKYN project, we will evaluate in the ABA model, the alteration of TRP-KYN metabolism in peripheral and central tissues, as well as in gut microbiota. Particularly, we will use a fluxomic approach after injection of labeled TRP that we recently developed. The effects of APA will be then assessed during refeeding in ABA mice on body composition, anxiety-like and depressive behavior. In parallel, a randomized control trial will be conducted in the Nutrition unit to evaluate the impact of APA in patients with AN on body composition, feeding behavior and anxiety and depressive behavior. Plasma and feces samples will be collected before and after APA. Finally, to decipher the role of gut microbiota in APA effects, we will perform fecal microbiota transplantation from patients to recipient mice. Indeed, gut microbiota also contributes to TRP-KYN metabolism. Thus the ANAKYN project is an ambitious program to evaluate the putative therapeutic opportunity of APA in patients with AN and to decipher the underlying mechanisms.