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

Abstract

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.

• Authors: Danny Ben-Zvi, Luca Meoli, Wasif M Abidi, Eirini Nestoridi, Courtney Panciotti, Erick Castillo, Palmenia Pizarro, Eleanor Shirley, William F Gourash, Christopher C Thompson, Rodrigo Munoz, Clary B Clish, Ron C Anafi, Anita P Courcoulas, Nicholas Stylopoulos
• Journal: Cell metabolism (Cell Metab) Vol. 28 Issue 2 Pg. 310-323.e6 (08 07 2018) ISSN: 1932-7420 [Electronic] United States
• PMID: 30043755 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• HIF1A protein, human
• Hif1a protein, mouse
• Hypoxia-Inducible Factor 1, alpha Subunit

Topics

• Adipose Tissue, White (metabolism)
• Anastomosis, Roux-en-Y (rehabilitation)
• Animals
• Diet, Reducing (methods)
• Female
• Gastric Bypass (rehabilitation)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Intestine, Small (metabolism)
• Liver (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Obese
• Middle Aged
• Muscle, Skeletal (metabolism)
• Obesity, Morbid (diet therapy, metabolism, surgery)
• Time
• Transcriptome
• Weight Loss (physiology)