Poster présenté par Brigitte Raux, Doctorante à l’EIPL, sous la direction de J.F Cavalier, lors du 12ème Congrès Euro Fed Lipid, 14-17 septembre 2014 à Montpellier, (Projet LISA)
Brigitte Raux (1), Véronique Point (1), Carole Vaysse (2), F. Carrière (1), L. Couëdelo (2), Jean-François Cavalier (1)
1) CNRS, Aix-Marseille Université - Enzymologie Interfaciale et Physiologie de la Lipolyse - UMR 7282 - Marseille, France
2) Equipe Nutrition, Métabolisme & Santé - ITERG - Bordeaux, France
The number of obese people has significantly increased to reach around 25% of the worldwide population. The digestion of dietary lipids mainly results from the hydrolytic activities of gastric (HGL) and pancreatic (HPL) lipases acting in the stomach and the small intestine, respectively. The only anti-obesity drug remaining on the market is the lipase inhibitor Orlistat (Xenical® by Roche and Alli® by GSK). This drug however blocks all known lipases and its apparent selectivity for gastrointestinal lipases is only due to the fact it is not absorbed when taken orally and thus only inhibits the enzymes found in GI tract lumen. Designing more selective inhibitors of digestive lipases remains however a challenge of fundamental value for better understanding of individual lipase function, but can also provide potential drug candidates aiming at the “fight against obesity”. In this competitive context, we recently reported that Oxadiazolone derivatives selectively and efficiently inhibit HGL, with no significant effects on HPL activity. In this context, the use of such compounds specifically designed to block gastric lipase without impacting the action of pancreatic lipase, and vice versa, should allow us to investigate the respective direct effects of each lipase on the overall lipolysis process. In particular, the loss of gastric lipolysis should slow down the overall lipolytic process and trigger satiety mechanisms via the so-called ileal brake, therefore providing a potential indirect approach to the treatment of obesity based on the reduction of food intake.