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

Cell Metab 2018 08 28;28(2):310-323.e6. Epub 2018 Jun 28.

Center for Basic and Translational Obesity Research, Division of Endocrinology, CLS16066, Boston Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address:

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.

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http://dx.doi.org/10.1016/j.cmet.2018.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628900PMC
August 2018
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