IGlucagon-Like Peptide-1 Receptor Agonism, but not Cannabanoid Receptor-Type 1 Antagonism, Improves Adjustable Gastrict Banding in Rats
6/10/2012 12:00:00 PM
6/10/2012 2:00:00 PM
, HENRIETTE KIRCHNER, CHUN-XIA YI, JENNA HOLLAND, NICKKI OTTAWAY, ERIN BARTLEY, PAUL T. PFLUGER, DIEGO PEREZ-TILVE, DAVID A.. D'ALESSIO, RANDY J.. SEELEY, MATTHIAS H. TSCHOP,
Several bariatric operations are currently used to treat obesity and its related comorbidities. Among these interventions, adjustable gastric banding (AGB) and Roux en-Y gastric bypass (RYGB) surgery are the most commonly used. AGB provides a safer, less invasive alternative to RYGB; however, it is far less effective and weight regain after surgery is a considerable problem. Nonetheless, AGB is significantly more effective than the few medications now available for weight loss. Glucagon-like peptide (GLP)-1 receptor agonists, such as exenatide (Ex4) and liraglutide, are useful to lower blood glucose and also cause reduced food intake and weight loss. As with AGB, GLP1-R agonism is also far less effective than RYGB. We hypothesized that the gap between RYGB and less invasive treatments could be closed through combination therapy. We tested this hypothesis by stimulating body weight loss via combined AGB and Ex4 therapy in diet-induce obese rats. Adult, male, DIO Long-Evans rats received either an AGB, or a sham surgery. In sham and AGB rats, 6 days of Ex4 treatment induced a similar decrease in BW compared to vehicle controls. Subsequent band inflation, at volumes that were sub-threshold for decreased food intake, did not lead to further body weight loss in vehicle treated rats, but synergistically enhanced Ex4 treatment. Reversal of treatment order (inflation before Ex4) stimulated similar trends in body weight loss. Interestingly, cannabinoid receptor-type 1 (CB1) antagonism, which induced similar decreases in food intake and body weight, was ineffective as a synergist to AGB. Immunohistochemical analysis of c-fos in the hindbrains of rats after band inflation uncovered activation of neurons in the nucleus solitary tract (NTS). Together these data suggest that AGB induces activity in the NTS of the hindbrain and that AGB-stimulated weight loss can be enhanced by the addition of GLP1-R agonism, but not by the antagonism of CB1 receptors.
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