GLP-1 receptor signaling is not required for reduced body weight after RYGB in rodents.

Abstract

Exaggerated GLP-1 and PYY secretion is thought to be a major mechanism in the reduced food intake and body weight after Roux-en-Y gastric bypass surgery. Here, we use complementary pharmacological and genetic loss-of-function approaches to test the role of increased signaling by these gut hormones in high-fat diet-induced obese rodents. Chronic brain infusion of a supramaximal dose of the selective GLP-1 receptor antagonist exendin-9-39 into the lateral cerebral ventricle significantly increased food intake and body weight in both RYGB and sham-operated rats, suggesting that, while contributing to the physiological control of food intake and body weight, central GLP-1 receptor signaling tone is not the critical mechanism uniquely responsible for the body weight-lowering effects of RYGB. Central infusion of the selective Y2R-antagonist BIIE0246 had no effect in either group, suggesting that it is not critical for the effects of RYGB on body weight under the conditions tested. In a recently established mouse model of RYGB that closely mimics surgery and weight loss dynamics in humans, obese GLP-1R-deficient mice lost the same amount of body weight and fat mass and maintained similarly lower body weight compared with wild-type mice. Together, the results surprisingly provide no support for important individual roles of either gut hormone in the specific mechanisms by which RYGB rats settle at a lower body weight. It is likely that the beneficial effects of bariatric surgeries are expressed through complex mechanisms that require combination approaches for their identification.

• Authors: Jianping Ye, Zheng Hao, Michael B Mumphrey, R Leigh Townsend, Laurel M Patterson, Nicholas Stylopoulos, Heike Münzberg, Christopher D Morrison, Daniel J Drucker, Hans-Rudolf Berthoud
• Journal: American journal of physiology. Regulatory, integrative and comparative physiology (Am J Physiol Regul Integr Comp Physiol) Vol. 306 Issue 5 Pg. R352-62 (Mar 01 2014) ISSN: 1522-1490 [Electronic] United States
• PMID: 24430883 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Benzazepines
• Dietary Fats
• GLP1R protein, human
• Glp1r protein, mouse
• Glp1r protein, rat
• Glucagon-Like Peptide-1 Receptor
• Peptide Fragments
• Receptors, Glucagon
• exendin (9-39)
• Arginine
• BIIE 0246

Topics

• Animals
• Arginine (administration & dosage, analogs & derivatives, pharmacology)
• Benzazepines (administration & dosage, pharmacology)
• Body Composition
• Body Weight (drug effects)
• Dietary Fats
• Eating
• Energy Metabolism
• Gastric Bypass
• Glucagon-Like Peptide-1 Receptor
• Male
• Mice
• Mice, Knockout
• Motor Activity
• Obesity (metabolism, surgery)
• Oxygen Consumption
• Peptide Fragments (administration & dosage, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Glucagon (antagonists & inhibitors, genetics, metabolism)
• Weight Loss (physiology)