Time-Dependent Molecular Responses Differ between Gastric Bypass and Dieting but Are Conserved Across Species

The effectiveness of Roux-en-Y gastric bypass (RYGB) against obesity and its comorbidities has generated excitement about developing new, less invasive treatments that use the same molecular mechanisms. Although controversial, RYGB-induced improvement of metabolic function may not depend entirely upon weight loss. To elucidate the differences between RYGB and dieting, we studied several individual organ molecular responses and generated an integrative, interorgan view of organismal physiology. We also compared murine and human molecular signatures. We show that, although dieting and RYGB can bring about the same degree of weight loss, post-RYGB physiology is very different. RYGB induces distinct, organ-specific adaptations in a temporal pattern that is characterized by energetically demanding processes, which may be coordinated by HIF1a activation and the systemic repression of growth hormone receptor signaling. Many of these responses are conserved in rodents and humans and may contribute to the remarkable ability of surgery to induce and sustain metabolic improvement. Using an integrative, interorgan view of organismal physiology, Ben-Zvi et al. compared RYGB gastric bypass and dieting in mouse and humans. Although dieting and RYGB can bring about the same degree of weight loss, the molecular signature of surgery highlights an essential role for metabolic regulators and the circadian clock.