Introduction Cholecystokinin (CCK), a gut peptide released postprandially from the small intestine, has been shown to reduce food intake and slow gastric emptying (GE) in man. Resistance to gut peptides involved in energy homeostasis such as leptin has also been demonstrated in obese individuals. Similarly, a reduction in sensitivity to CCK may lead to increased food intake and ultimately affect body weight. It is not known if the effects of CCK are consistent between obese and lean individuals. The aim of this study was to determine the effect of the CCK1 receptor antagonist, dexloxiglumide, on GE of a nutrient releasing meal, in lean and obese subjects.
Methods Ten obese (BMI; 47 kg/m2 ±7) and 10 non-obese (BMI; 22 kg/m2 ±2) participants ingested the CCK1 receptor antagonist, dexloxiglumide, or placebo. An hour later, 500 ml of skimmed milk containing 13C-acetate was consumed. A 13C-acetate breath test was used as a proxy measure for the rate of GE.
Results GE of skimmed milk was slower in obese subjects when compared to lean subjects in both placebo (p=0.013) and dexloxiglumide conditions (p=0.017). When compared to placebo, dexloxiglumide accelerated GE of skimmed milk in both lean (p=0.034) and obese subjects (p=0.022), however, the percentage increase in GE rate with dexloxiglumide vs placebo was greater in obese compared to the lean subjects (p=0.017). There was a direct relationship between the rate of GE and BMI in both placebo (p=0.00), and dexloxiglumide conditions (p=0.04).
Conclusion These results demonstrate that the response to dexloxiglumide does not appear to be reduced, but rather increased in obese subjects, suggesting that sensitivity to CCK is not impaired in obesity. These results also suggest an overall slower rate of GE in obese compared to lean subjects, which could be a contributing factor in the pathogenesis of obesity.
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