Abstract
BackgroundThe impact of Roux-en-Y gastric bypass (RYGB) on type 2 diabetes mellitus is thought to result from upper and/or lower gut hormone alterations. Evidence supporting these mechanisms is incomplete, in part because of limitations in relevant bariatric-surgery animal models, specifically the lack of naturally insulin-resistant large animals. With overfeeding, Ossabaw swine develop a robust metabolic syndrome, and may be suitable for studying post-surgical physiology. Whether bariatric surgery is feasible in these animals with acceptable survival is unknown.MethodsThirty-two Ossabaws were fed a high-fat, high-cholesterol diet to induce obesity and insulin resistance. These animals were assigned to RYGB (n = 8), RYGB with vagotomy (RYGB-V, n = 5), gastrojejunostomy (GJ, n = 10), GJ with duodenal exclusion (GJD, n = 7), or sham operation (n = 2) and were euthanized 60 days post-operatively. Post-operative changes in weight and food intake are reported.ResultsSurvival to scheduled necropsy among surgical groups was 77%, living an average of 57 days post-operatively. Cardiac arrest under anesthesia occurred in 4 pigs. Greatest weight loss (18.0% ± 6%) and food intake decrease (57.0% ± 20%) occurred following RYGB while animals undergoing RYGB-V showed only 6.6% ± 3% weight loss despite 50.8% ± 25% food intake decrease. GJ (12.7% ± 4%) and GJD (1.2% ± 1%) pigs gained weight, but less than sham controls (13.4% ± 10%).ConclusionsA survival model of metabolic surgical procedures is feasible, leads to significant weight loss, and provides the opportunity to evaluate new interventions and subtle variations in surgical technique (e.g. vagus nerve sparing) that may provide new mechanistic insights.
Highlights
Roux-en-Y gastric bypass surgery (RYGB) promotes substantial, sustained weight loss [1] [2], and it is the most effective method to ameliorate obesity-related comorbidity including type 2 diabetes mellitus (T2DM) [3]-[5]
In obese Ossabaw pigs, we describe our initial experience with long-term survival surgery including RYGB without vagotomy, RYGB with vagotomy (RYGB-V), gastrojejunostomy with duodenal exclusion (GJD, which creates a gastricsparing bypass of the segment of proximal intestine excluded in RYGB), and gastrojejunostomy (GJ, which is identical to the latter operation with duodenal inclusion)
All experimental procedures involving animals were approved by the Institutional Animal Care and Use Committee at the University of Washington (UW) with the recommendations outlined by the National Research Council and the American Veterinary Medical Association Panel on Euthanasia [20] [21]
Summary
Roux-en-Y gastric bypass surgery (RYGB) promotes substantial, sustained weight loss [1] [2], and it is the most effective method to ameliorate obesity-related comorbidity including type 2 diabetes mellitus (T2DM) [3]-[5]. The impact of Roux-en-Y gastric bypass (RYGB) on type 2 diabetes mellitus is thought to result from upper and/or lower gut hormone alterations. Evidence supporting these mechanisms is incomplete, in part because of limitations in relevant bariatric-surgery animal models, the lack of naturally insulin-resistant large animals. Methods: Thirty-two Ossabaws were fed a high-fat, high-cholesterol diet to induce obesity and insulin resistance These animals were assigned to RYGB (n = 8), RYGB with vagotomy (RYGB-V, n = 5), gastrojejunostomy (GJ, n = 10), GJ with duodenal exclusion (GJD, n = 7), or sham operation (n = 2) and were euthanized 60 days post-operatively. Conclusions: A survival model of metabolic surgical procedures is feasible, leads to significant weight loss, and provides the opportunity to evaluate new interventions and subtle variations in surgical technique (e.g. vagus nerve sparing) that may provide new mechanistic insights
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