title: GLP-1R responsiveness predicts individual gastric bypass efficacy on glucose tolerance in rats.
abstract: 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.
authors.affiliation: Metabolic Diseases Institute, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Cincinnati, Cincinnati, OH.
authors.forename: Kirk M
authors.initials: KM
authors.lastname: Habegger
authors.forename: Kristy M
authors.initials: KM
authors.lastname: Heppner
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Amburgy
authors.forename: Nickki
authors.initials: N
authors.lastname: Ottaway
authors.forename: Jenna
authors.initials: J
authors.lastname: Holland
authors.forename: Christine
authors.initials: C
authors.lastname: Raver
authors.forename: Erin
authors.initials: E
authors.lastname: Bartley
authors.forename: Timo D
authors.initials: TD
authors.lastname: Müller
authors.forename: Paul T
authors.initials: PT
authors.lastname: Pfluger
authors.forename: Jose
authors.initials: J
authors.lastname: Berger
authors.forename: Mouhamadoul
authors.initials: M
authors.lastname: Toure
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Benoit
authors.forename: Richard D
authors.initials: RD
authors.lastname: Dimarchi
authors.forename: Diego
authors.initials: D
authors.lastname: Perez-Tilve
authors.forename: David A
authors.initials: DA
authors.lastname: D'Alessio
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Seeley
authors.forename: Matthias H
authors.initials: MH
authors.lastname: Tschöp
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000009:adverse effects; D004435:Eating; D000077270:Exenatide; D015390:Gastric Bypass; D005786:Gene Expression Regulation / Q000502:physiology; D000067757:Glucagon-Like Peptide-1 Receptor; D005951:Glucose Tolerance Test; D008297:Male; D009765:Obesity; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D018027:Receptors, Glucagon / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D014688:Venoms / Q000494:pharmacology; D015431:Weight Loss
chemical_list: D004041:Dietary Fats; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D000077270:Exenatide