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.
Bibliographical noteFunding Information:
This study was supported by NIH ( R01-DK108642 , N.S., A.P.C.), Edward Mallinckrodt Jr. Foundation (N.S.), Diabetes Action Research and Education Foundation (N.S.), Rothschild fellowship (D.B.-Z.) and Human Frontiers in Science post-doctoral fellowship (D.B.-Z.), the National Fund for Scientific and Technological Development of the Government of Chile ( FONDECYT 11160688 , R.M.; and P30-DK034854 ). We would like to thank: Dr. Douglas Melton for thoughtful discussions and support with the RNA-sequencing studies; A. Steuernagel, J. Palsgaard, and T. Siegmund of EvoTec for assistance in analysis; N. Saeidi, J. Koschwanez, S. Kvas, L. Lin, and I. Koren for technical assistance; Hannah Whitley for administrative assistance.
© 2018 Elsevier Inc.
- bariatric surgery
- circadian clock
- gastric bypass
- growth hormone signaling
- intestinal metabolism