Abstract
Background
The mechanisms by which Roux-en-Y gastric bypass surgery (RYGB) so effectively lowers body weight and improves glycemic control are not well understood, and murine models are essential for identifying the crucial signaling pathways involved. The aim of this study is to characterize the time course of RYGB on body weight, body composition, food intake, and energy expenditure in diet-induced obese mice and establish a tissue bank for global “omics” or targeted biochemical and structural analyses.
Methods
High-fat diet-induced obese mice were subjected to RYGB using an improved surgical technique with a small gastric pouch. The effects on body weight, body composition, food intake, and energy expenditure were compared to sham surgery, high-fat diet-restricted weight-matched controls, and never-obese chow-fed controls.
Results
Without mortality or complications, RYGB surgery in high-fat diet-induced obese mice gradually decreased body weight to a plateau that was more or less sustained for up to 12 weeks (33 g, −18 %, p < 0.01) and significantly lower compared with sham-operated mice (51 g, +25 %, p < 0.01), but higher (+18 %, p < 0.01) than age-matched, chow-fed control mice (27 g). Energy intake after RYGB was significantly suppressed compared to sham only for the first 10 days, but significantly higher compared to weight-matched mice. Energy expenditure after RYGB was higher throughout the study compared with weight-matched, but not sham animals.
Conclusions
RYGB surgery in diet-induced obese mice results in similar body weight and body composition changes as observed in humans, but in contrast with humans, this is achieved mainly through increased energy expenditure rather than decreased food intake.
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References
Meguid MM, Ramos EJ, Suzuki S, Xu Y, George ZM, Das UN, et al. A surgical rat model of human Roux-en-Y gastric bypass. J Gastrointest Surg. 2004;8:621–30.
Stylopoulos N, Hoppin AG, Kaplan LM. Roux-en-Y gastric bypass enhances energy expenditure and extends lifespan in diet-induced obese rats. Obesity (Silver Spring). 2009;17:1839–47.
Bueter M, Lowenstein C, Olbers T, Wang M, Cluny NL, Bloom SR, et al. Gastric bypass increases energy expenditure in rats. Gastroenterology. 2010;138:1845–53.
Hajnal A, Kovacs P, Ahmed TA, Meirelles K, Lynch CJ, Cooney RN. Gastric bypass surgery alters behavioral and neural taste functions for sweet taste in obese rats. Am J Physiol Gastrointest Liver Physiol. 2010;299:G967–79.
Zheng H, Shin AC, Lenard NR, Townsend RL, Patterson LM, Sigalet DL, et al. Meal patterns, satiety, and food choice in a rat model of Roux-en-Y gastric bypass surgery. Am J Physiol Regul Integr Comp Physiol. 2009;297:R1273–82.
Meirelles K, Ahmed T, Culnan DM, Lynch CJ, Lang CH, Cooney RN. Mechanisms of glucose homeostasis after Roux-en-Y gastric bypass surgery in the obese, insulin-resistant Zucker rat. Ann Surg. 2009;249:277–85.
Nestoridi E, Kvas S, Kucharczyk J, Stylopoulos N. Resting energy expenditure and energetic cost of feeding are augmented after Roux-en-Y gastric bypass in obese mice. Endocrinology. 2012;153:2234–44.
Zechner JF, Mirshahi UL, Satapati S, Berglund ED, Rossi J, Scott MM, et al. Weight-independent effects of roux-en-Y gastric bypass on glucose homeostasis via melanocortin-4 receptors in mice and humans. Gastroenterology. 2013;144:580–90. e587.
Liou AP, Paziuk M, Luevano Jr JM, Machineni S, Turnbaugh PJ, Kaplan LM. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci Transl Med. 2013;5:178ra141.
Hao Z, Zhao Z, Berthoud HR, Ye J. Development and verification of a mouse model for Roux-en-Y gastric bypass surgery with a small gastric pouch. PLoS ONE. 2013;8:e52922.
Reddy IA, Wasserman DH, Ayala JE, Hasty AH, Abumrad NN, Galli A. Striatal dopamine homeostasis is altered in mice following Roux-en-Y gastric bypass surgery. ACS Chem Neurosci. 2014;5:943–51.
Verbeek J, Lannoo M, Pirinen E, Ryu D, Spincemaille P, Vander Elst I, et al. Roux-en-y gastric bypass attenuates hepatic mitochondrial dysfunction in mice with non-alcoholic steatohepatitis. Gut. 2015;64:673–83.
Chambers AP, Kirchner H, Wilson-Perez HE, Willency JA, Hale JE, Gaylinn BD, et al. The effects of vertical sleeve gastrectomy in rodents are ghrelin independent. Gastroenterology. 2013;144:50–2. e55.
Hao Z, Munzberg H, Rezai-Zadeh K, Keenan M, Coulon D, Lu H, et al. Leptin deficient ob/ob mice and diet-induced obese mice responded differently to Roux-en-Y bypass surgery. Int J Obes (Lond). 2015;39:798–805.
Neinast MD, Frank AP, Zechner JF, Li Q, Vishvanath L, Palmer BF, et al. Activation of natriuretic peptides and the sympathetic nervous system following Roux-en-Y gastric bypass is associated with gonadal adipose tissues browning. Mol Metab. 2015;4:427–36.
Chang SH, Stoll CR, Song J, Varela JE, Eagon CJ, Colditz GA. The effectiveness and risks of bariatric surgery: an updated systematic review and meta-analysis, 2003–2012. JAMA Surg. 2014;149:275–87.
Courcoulas AP, Christian NJ, Belle SH, Berk PD, Flum DR, Garcia L, et al. Weight change and health outcomes at 3 years after bariatric surgery among individuals with severe obesity. JAMA. 2013;310:2416–25.
Christou NV, Look D, Maclean LD. Weight gain after short- and long-limb gastric bypass in patients followed for longer than 10 years. Ann Surg. 2006;244:734–40.
Ryan KK, Tremaroli V, Clemmensen C, Kovatcheva-Datchary P, Myronovych A, Karns R, et al. FXR is a molecular target for the effects of vertical sleeve gastrectomy. Nature. 2014;509:183–8.
Mokadem M, Zechner JF, Margolskee RF, Drucker DJ, Aguirre V. Effects of Roux-en-Y gastric bypass on energy and glucose homeostasis are preserved in two mouse models of functional glucagon-like peptide-1 deficiency. Mol Metab. 2014;3:191–201.
Sjostrom L. Bariatric surgery and reduction in morbidity and mortality: experiences from the SOS study. Int J Obes (Lond). 2008;32 Suppl 7:S93–7.
Laurenius A, Larsson I, Melanson KJ, Lindroos AK, Lönroth H, Bosaeus I, et al. Decreased energy density and changes in food selection following Roux-en-Y gastric bypass. Eur J Clin Nutr. 2013;67:168–73.
Ortega J, Ortega-Evangelio G, Cassinello N, Sebastia V. What are obese patients able to eat after Roux-en-Y gastric bypass? Obes Facts. 2012;5:339–48.
Schmidt JB, Pedersen SD, Gregersen NT, Vestergaard L, Nielsen MS, Ritz C, et al. Effects of RYGB on energy expenditure, appetite and glycemic control: a randomized controlled clinical trial. Int J Obes (Lond) 2015 (Epub ahead of print).
Odstrcil EA, Martinez JG, Santa Ana CA, Xue B, Schneider RE, Steffer KJ, et al. The contribution of malabsorption to the reduction in net energy absorption after long-limb Roux-en-Y gastric bypass. Am J Clin Nutr. 2010;92:704–13.
Thivel D, Brakonieki K, Duche P, Morio B, Boirie Y, Laferrere B. Surgical weight loss: impact on energy expenditure. Obes Surg. 2013;23:255–66.
Munzberg H, Laque A, Yu S, Rezai-Zadeh K, Berthoud HR. Appetite and body weight regulation after bariatric surgery. Obes Rev. 2015;16 Suppl 1:77–90.
Jackness C, Karmally W, Febres G, Conwell IM, Ahmed L, Bessler M, et al. Very low calorie diet mimics the early beneficial effect of Roux-en-Y gastric bypass on insulin sensitivity and beta-cell function in type 2 diabetic patients. Diabetes. 2013;62:3027–32.
Isbell JM, Tamboli RA, Hansen EN, Saliba J, Dunn JP, Phillips SE, et al. The importance of caloric restriction in the early improvements in insulin sensitivity after Roux-en-Y gastric bypass surgery. Diabetes Care. 2010;33:1438–42.
Acknowledgments
This study was supported by the National Institutes of Health grant DK047348 (HRB), DK085495 (JY) and the NORC DK072476 Metabolism and Physiology Core.
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Animal care and experimentation was approved by the Pennington Biomedical Research Center Institutional Animal Care and Use Committee and strictly followed rules and guidelines provided by the American Physiological Society and NIH.
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The authors declare that they have no conflict of interest.
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Hao, Z., Mumphrey, M.B., Townsend, R.L. et al. Body Composition, Food Intake, and Energy Expenditure in a Murine Model of Roux-en-Y Gastric Bypass Surgery. OBES SURG 26, 2173–2182 (2016). https://doi.org/10.1007/s11695-016-2062-y
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DOI: https://doi.org/10.1007/s11695-016-2062-y