In an animal model, diet induced obese animals exhibiting metabolic syndrome underwent Roux-en-Y gastric bypass with highly reproducible surgical outcomes as well as biochemical and energetic homeostatic abnormalities similar to post-RYGB findings in humans. Weight regain occurs in approximately 20% of patients after two to three years after RYGB. It seems that the weight-loss-promoting effects of chronically elevated plasma PYY concentrations dominate the weight-gain-promoting effects of lowered plasma leptin concentrations, with the relative plasma PYY: leptin concentration ratio determining whether weight loss will be sustained or regained.