Submitted on March 8, 2007
Accepted on June 28, 2007
Characterization of weight loss and weight regain mechanisms after Roux-en-Y gastric bypass in rats
Ana Guijarro1, Susumo Suzuki2, Chung Chen3, Henriette Kirchner2, Frank A. Middleton4, Sergiy Nadtochiy5, Paul S Brookes5, Akira Niijima6, Akio Inui7, and Michael M. Meguid2*
1 Surgical Metabolism and Nutrition Laboratory, Neuroscience Program, Department of Surgery, University Hospital, SUNY Upstate Medical University, Syracuse, New York, United States
2 Surgery Neuroscience Program, Surgical Metabolism and Nutrition Laboratory, Department of Surgery, University Hospital, SUNY Upstate Medical University, Syracuse, New York, United States
3 Department of Statistics, Management Information and Decision, Whitman School of Management, Syracuse University, Syracuse, New York, United States
4 Microarray Core Facility, Neuroscience Program, Dept. of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, New York, United States
5 Department of Anesthesiology & Mitochondrial Research Interest Group, University of Rochester Medical Center, Rochester, New York, United States
6 Department of Physiology, Niigata University, Niigata, Japan
7 Department of Behavioral Medicine, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, Japan
* To whom correspondence should be addressed. E-mail: meguidm{at}upstate.edu.
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 success (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. BW, caloric intake (CI) and fecal output (FO) were recorded daily for 90 days, food efficiency (FE) was calculated, and morphologic 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, 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 vs. Obese showed rapid BW decrease, followed by sustained BW loss in RYGB-S. RYGB-F and PF gradually increased BW. BW loss in RYGB-S rats is achieved not only by a RYGB-induced decreased CI and increased FO, but also via SNS activation, driven by increased PYY, CRF and orexin signaling, decreasing FE and energy storage, demonstrated by reduced fat mass associated with the up-regulation of mitochondrial UCP-2 in fat. These events override the compensatory response to the drop in leptin levels aimed at conserving energy.
