Résumé
Ghrelin is a hormone produced by cells of the gastrointestinal tract, especially the stomach. Ghrelin activates cells in the anterior pituitary gland and hypothalamus and increases the drive to eat. The level of circulating ghrelin impacts anxiety, stress, and aggression. Myostatin plays crucial roles in negative regulation of muscle growth. Inactivation of myostatin gene results in gross muscle hypertrophy. Ghrelin controls expression of myostatin in cancer and chronic heart failure - associated cachexia (1). We observed that myostatin KO are more aggressive than wild type animals. Butyrylcholinesterase (BCHE) is one of the enzymes responsible for the deacylation of ghrelin (2).BCHE-KO mice show higher level of acylated ghrelin and are more aggressive than wild–type mice (3). De-acylation of ghrelin by BCHE reduces aggression and social stress in mice. The link between circulating BCHE level with energetic expenditure and body composition is debated. Questions related to the role of myostatin in the control of other aspects of energy homeostasis beside muscular growth remain unanswered. Our goal is to establish the link between BCHE, ghrelin and level of expression of myostatin and if these could explain the behavior of the myostatin KO model. myostatin KO mice show less spontaneous activity and lower food intake than controls. We assessed the anxiety level using different tests (elevated plus maze and light/dark box). Our results show that myostatin KO mice explore less often and spend less time in open branches of the labyrinth. This anxious behavior is not accompanied by a change in circulating corticosterone. Our first analysis of resident/intruder tests, show that myostatin KO mice are more aggressive than wild type littermates. KO mice have less ghrelin and less acylated ghrelin especially in females. Females have a higher level of BCHE than males in both genotypes. But only female KO mice show lower level of BCHE compared to wild-type littermates. Reduced ghrelin levels could explain partly the behavior of our model.These preliminary results lead us to explore other pathways in the hypothalamo-pituitary-adrenal axis regulating aggression in myostatin KO mice. (1) Lenk K, Palus S, Schur R, Datta R, Dong J, Culler MD, Anker S, Springer J, Schuler G, Adams V. (2013) Effect of ghrelin and its analogues, BIM-28131 and BIM-28125, on the expression of myostatin in a rat heart failure model. J Cachexia Sarcopenia Muscle.;4(1):63-9.(2) Schopfer LM, Lockridge O, Brimijoin S (2015) Pure human butyrylcholinesterase hydrolyzes octanoyl ghrelin to desacyl ghrelin. Gen Comp Endocrinol. ;224:61-8(3) Brimijoin S, Chen VP, Pang YP, Geng L, Gao Y 2016 Physiological roles for butyrylcholinesterase: A BChE-ghrelin axis. Chem Biol Interact. 2016 Nov 25;259(Pt B):271-275