oa Chronic elevation of systemic glucagon-like peptide-1 following surgical weight loss: Association with nausea and vomiting and effects on adipokines

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.