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GLP-1R responsiveness predicts individual gastric bypass efficacy on glucose tolerance in rats.

Diabetes 63, 505-513 (2014)
Open Access Green as soon as Postprint is submitted to ZB.
Several bariatric operations are currently used to treat obesity and obesity-related comorbidities. These vary in efficacy, but most are more effective than current pharmaceutical treatments. Roux-en-Y Gastric Bypass (RYGB) produces substantial body weight (BW) loss, enhanced glucose tolerance, and is associated with increased secretion of the gut hormone GLP-1. Given the success of GLP-1-based agents in lowering blood glucose and BW, we hypothesized that an individual sensitivity to GLP-1 receptor agonism could predict metabolic benefits of surgeries associated with increased GLP-1 secretion. One hundred ninety-seven high-fat-diet-induced obese male Long-Evans rats were monitored for BW loss during Exendin-4 (Ex4) administration. Stable populations of responders and non-responders were identified based on Ex4-induced BW loss and GLP-1-induced improvements in glucose tolerance. Sub-populations of Ex4 extreme responders and non-responders received RYGB. Following RYGB, responders and non-responders showed similar BW loss compared to sham, but non-responders retained impaired glucose tolerance. These data indicate that the GLP-1 response tests may predict some but not all of the improvements observed after RYGB. These findings present an opportunity to optimize the use of bariatric surgery based on an improved understanding of GLP-1 biology and suggest an opportunity for a more personalized therapeutic approach to the metabolic syndrome.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Glucagon-like Peptide-1; Vertical Sleeve Gastrectomy; Weight-loss; Exenatide Treatment; Surgery; Obesity; Metaanalysis; Overweight
Reviewing status