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Am J Physiol Regul Integr Comp Physiol. 2014 Mar 1;306(5):R352-62. doi: 10.1152/ajpregu.00491.2013. Epub 2014 Jan 15.

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

Author information

1
Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana;

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.

KEYWORDS:

GLP-1R knockout; Roux-en-Y gastric bypass; brain; exendin-(9–39), BIIE0246; food intake; gut hormones; high-fat diet

PMID:
24430883
PMCID:
PMC3949077
DOI:
10.1152/ajpregu.00491.2013
[Indexed for MEDLINE]
Free PMC Article

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