Reprogramming of defended body weight after Roux‐En‐Y gastric bypass surgery in diet‐induced obese mice

Objective Roux‐en‐Y gastric bypass surgery (RYGB) results in sustained lowering of body weight in most patients, but the mechanisms involved are poorly understood. The aim of this study was to obtain support for the notion that reprogramming of defended body weight, rather than passive restriction of energy intake, is a fundamental mechanism of RYGB. Methods Male C57BL6J mice reaching different degrees of obesity on a high‐fat diet either with ad libitum access or with caloric restriction (weight‐reduced) were subjected to RYGB. Results RYGB‐induced weight loss and fat mass loss were proportional to pre‐surgical levels, with moderately obese mice losing less body weight and fat compared with very obese mice. Remarkably, mice that were weight‐reduced to the level of chow controls before surgery immediately gained weight after surgery, exclusively accounted for by lean mass gain. Conclusions The results provide additional evidence for reprogramming of a new defended body weight as an important principle by which RYGB lastingly suppresses body weight. RYGB appears to selectively abolish defense of a higher fat mass level, while remaining sensitive to the defense of lean mass. The molecular and physiological mechanisms underlying this reprogramming remain to be elucidated.