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 and enhanced
glucose tolerance, and is associated with increased secretion of the gut
hormone glucagon-like peptide 1 (GLP-1). Given the success of GLP-1-based agents in lowering
blood glucose levels 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 nonresponders were identified based on Ex4-induced BW loss and GLP-1-induced improvements in
glucose tolerance. Subpopulations of Ex4 extreme responders and nonresponders underwent RYGB surgery. After RYGB, responders and nonresponders showed similar BW loss compared with
sham, but nonresponders 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.