Gastric bypass surgery is the most effective treatment for obesity, achieving both sustained weight loss and improved insulin sensitivity. However, following Roux-en-Y gastric bypass surgery (RYGB) some patients develop debilitating nausea and vomiting (N/V) persisting for years. The aim of this study was to determine if the N/V following RYGB is due to elevated systemic GLP-1 levels and whether GLP-1 directly mediates secretion of adipokines, such as leptin. 42 female non-diabetic subjects were studied in the fasting and post-prandial state and divided into 5 groups according to BMI and presence of N/V post-operatively. The effect of GLP-1 on adipose tissue leptin secretion in vitro was measured. Subjects with N/V post-RYGB surgery had significantly elevated fasting GLP-1 levels compared to post-operative subjects without N/V symptoms, and to morbidly obese (MO), obese and lean subjects not undergoing surgery. However, weight loss, as well as systemic levels of glucose, insulin and post-prandial GLP-1 was similar in all post-operative subjects. Despite similar BMI (P = 0.86) and fasting adiponectin levels, leptin was significantly lower in subjects with N/V compared to those without N/V (P = 0.04). Leptin secretion from subcutaneous adipose tissue in vitro was significantly inhibited by GLP-1 (0.1-1.0 nM; n = 6). Persistent N/V following RYGB surgery is associated with elevated fasting GLP-1 and lower leptin levels, perhaps as a consequence of GLP-1 mediated inhibition of leptin secretion from adipose tissue. GLP-1 antagonists may alleviate these symptoms, but, adverse effects on weight maintenance and insulin sensitivity need to be considered.


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