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Am J Physiol Regul Integr Comp Physiol 293: R1474-R1489, 2007. First published July 11, 2007; doi:10.1152/ajpregu.00171.2007
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APPETITE, OBESITY, DIGESTION, AND METABOLISM

Characterization of weight loss and weight regain mechanisms after Roux-en-Y gastric bypass in rats

Ana Guijarro,1 Susumu Suzuki,1 Chung Chen,2 Henriette Kirchner,1 Frank A. Middleton,3 Sergiy Nadtochiy,4 Paul S. Brookes,4 Akira Niijima,5 Akio Inui,6 and Michael M. Meguid1

1Surgical Metabolism and Nutrition Laboratory, Neuroscience Program, Department of Surgery, University Hospital, State University of New York (SUNY) Upstate Medical University; 2Department of Statistics, Management Information, and Decision, Whitman School of Management, Syracuse University; 3Microarray Core Facility, Neuroscience Program, Physiology Department, SUNY Upstate Medical University, Syracuse; 4Department of Anesthesiology and Mitochondrial Research Interest Group, University of Rochester Medical Center, Rochester, New York; and 5Department of Physiology, Niigata University, Niigata and 6Department of Behavioral Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragtaoka, Kagoshima, Japan

Submitted 8 March 2007 ; accepted in final form 28 June 2007

Roux-en-Y gastric bypass (RYGB) is the most effective therapy for morbid obesity, but it has a ~20% failure rate. To test our hypothesis that outcome depends on differential modifications of several energy-related systems, we used our established RYGB model in Sprague-Dawley diet-induced obese (DIO) rats to determine mechanisms contributing to successful (RGYB-S) or failed (RYGB-F) RYGB. DIO rats were randomized to RYGB, sham-operated Obese, and sham-operated obese pair-fed linked to RYGB (PF) groups. Body weight (BW), caloric intake (CI), and fecal output (FO) were recorded daily for 90 days, food efficiency (FE) was calculated, and morphological changes were determined. D-Xylose and fat absorption were studied. Glucose-stimulated vagal efferent nerve firing rates of stomach were recorded. Gut, adipose, and thyroid hormones were measured in plasma. Mitochondrial respiratory complexes in skeletal muscle and expression of energy-related hypothalamic and fat peptides, receptors, and enzymes were quantified. A 25% failure rate occurred. RYGB-S, RYGB-F, and PF rats showed rapid BW decrease vs. Obese rats, followed by sustained BW loss in RYGB-S rats. RYGB-F and PF rats gradually increased BW. BW loss in RYGB-S rats is achieved not only by RYGB-induced decreased CI and increased FO, but also via sympathetic nervous system activation, driven by increased peptide YY, CRF, and orexin signaling, decreasing FE and energy storage, demonstrated by reduced fat mass associated with the upregulation of mitochondrial uncoupling protein-2 in fat. These events override the compensatory response to the drop in leptin levels aimed at conserving energy.

food efficiency; gut and adipose hormones; mitochondria; obesity



Address for reprint requests and other correspondence: M. M. Meguid, Dept. of Surgery, University Hospital, 750 East Adams St., Syracuse, NY 13210 (e-mail: meguidm{at}upstate.edu)







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