Probing the mechanisms of the metabolic effects of weight loss surgery in humans using a novel mouse model system.

Gastrointestinal weight loss surgery, especially Roux-en-Y gastric bypass (RYGB), is the most effective treatment for severe obesity. RYGB is associated with a remarkable decrease in the rate of death from obesity-related complications, such as diabetes mellitus, coronary artery disease, and cancer. Dissecting the mechanisms of RYGB effects could augment our understanding about the pathogenesis of obesity and its complications.In this study, we describe in detail a mouse model of RYGB that closely reproduces the surgical steps of the human procedure.We show that RYGB in mice has the same effects as in human patients, proving the high translational validity of this model system. We present an intraoperative video to facilitate the widespread use of this complex and difficult method.The study of the mechanisms of RYGB using this model system can greatly facilitate our understanding about the effects of RYGB in human patients. The reverse engineering of the physiological mechanisms of RYGB could lead to discovery of new, effective, and less invasive treatments.