Can medical therapy mimic the clinical efficacy or physiological effects of bariatric surgery?

The number of bariatric surgical procedures performed has increased dramatically. This review discusses the clinical and physiological changes, and in particular, the mechanisms behind weight loss and glycaemic improvements, observed following the gastric bypass, sleeve gastrectomy and gastric banding bariatric procedures. The review then examines how close we are to mimicking the clinical or physiological effects of surgery through less invasive and safer modern interventions that are currently available for clinical use. These include dietary interventions, orlistat, lorcaserin, phentermine/topiramate, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, pramlintide, dapagliflozin, the duodenal–jejunal bypass liner, gastric pacemakers and gastric balloons. We conclude that, based on the most recent trials, we cannot fully mimic the clinical or physiological effects of surgery; however, we are getting closer. A ‘medical bypass' may not be as far in the future as we previously thought, as the physician's armamentarium against obesity and type 2 diabetes has recently got stronger through the use of specific dietary modifications, novel medical devices and pharmacotherapy. Novel therapeutic targets include not only appetite but also taste/food preferences, energy expenditure, gut microbiota, bile acid signalling, inflammation, preservation of β-cell function and hepatic glucose output, among others. Although there are no magic bullets, an integrated multimodal approach may yield success. Non-surgical interventions that mimic the metabolic benefits of bariatric surgery, with a reduced morbidity and mortality burden, remain tenable alternatives for patients and health-care professionals

Body Composition, Food Intake, and Energy Expenditure in a Murine Model of Roux-en-Y Gastric Bypass Surgery

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. AIMS: 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 to humans, this is achieved mainly through increased energy expenditure rather than decreased food intake

Lessons learned from gastric bypass operations in rats

Numerous studies using gastric bypass rat models have been recently conducted to uncover underlying physiological mechanisms of Roux-en-Y gastric bypass. Reflecting on lessons learned from gastric bypass rat models may thus aid the development of gastric bypass models in mice and other species. This review aims to discuss technical and experimental details of published gastric bypass rat models to understand advantages and limitations of this experimental tool. The review is based on PubMed literature using the search terms 'animal model', 'rodent model', 'bariatric surgery', 'gastric bypass', and 'Roux-en-Y gastric bypass'. All studies published up until February 2011 were included. 32 studies describing 15 different rat gastric bypass models were included. Description of surgical technique differs in terms of pouch size, limb lengths, preservation of the vagal nerve, and mortality rate. Surgery was carried out exclusively in male rats of different strains and ages. Pre- and postoperative diets also varied significantly. Technical and experimental variations in published gastric bypass rat models complicate comparison and identification of potential physiological mechanisms involved in gastric bypass. In summary, there is no clear evidence that any of these models is superior, but there is an emerging need for standardization of the procedure to achieve consistent and comparable data