Effect of amino acids supplementation in the activity-based anorexia model ; Etude de l'impact de supplémentations en acides aminés dans un modèle murin d'anorexie associé à une activité physique.

Anorexia nervosa (AN) is one of the main eating disorders described in DSM-V occurring in female population and characterized by a severe caloric restriction. AN is quite frequently associated with mood disorders, physical hyperactivity and functional digestive disorders. In addition, AN has the highest mortality rate among all mental disorders and high risk of relapse. The aim of this thesis was to assess the effects of amino acids oral supplementations as glutamine (Gln) and branched-chain amino acids (BCAA) in the activity-based anorexia (ABA) mice model. ABA mice share some common features with AN patients as severe weight loss, physical hyperactivity and delayed gastric emptying. When supplied for seven days with Gln, paracellular permeability, total protein synthesis and mucin-2 mRNA level were restored in the ABA mice colon. However, no beneficial effect was found with BCAA which seemed decrease the colonic protein synthesis. Body weight and body composition were not affected by Gln or BCAA and we hypothesized that caloric supply was not enough to induce body weight gain. Thus, we aimed to test our hypothesis with a combination of a progressive refeeding and Gln or BCAA supplementation. Refeeding partially restored body weight and lean mass in ABA mice with a rebound of fat mass but Gln had no additional effect. Nevertheless, BCAA tended to increase fat mass, and then body weight, in comparison to refeeding alone. Plasma leptin was restored in refed mice, without an effect of amino acids supplementation, while only Gln normalized plasma triglycerides. BCAA supplementation tended to increase glycaemia and cholesterolemia. Here, we confirmed the beneficial effects of Gln in the colon observed in our first study. Gln amplified the effects of refeeding on colonic total protein synthesis, p70S6kinase phosphorylation and tight junction proteins as claudin-1 and occludin. Conversely, BCAA appeared to alleviate, or cancel, the benefits of refeeding on these parameters. Given these data, Gln is thought to be of ...