Preoperative mu-opioid receptor availability predicts weight loss following bariatric surgery

Abstract

Background: Bariatric surgery is the most effective method for weight loss in morbid obesity. There is significant individual variability in the weight loss outcomes, yet factors leading to postoperative weight loss or weight regain remain elusive. Alterations in the mu-opioid receptor (MOR) and dopamine D2 receptor (D2R) systems are associated with obesity, appetite control, and reward processing. The magnitude of initial brain receptor system perturbation is a plausible predictor of long-term surgical weight loss outcomes. The aim was to test this hypothesis by measuring obese subjects MOR and D2R availability with positron emission tomography (PET) preoperatively before bariatric surgery and then assessing their weight development association with regional MOR and D2R availabilities at 2-year follow-up. Methods: We studied 19 morbidly obese women (mean BMI 40, mean age 43) scheduled to undergo bariatric surgery, i.e. Roux-en-Y gastric bypass or sleeve gastrectomy, according to their standard clinical treatment. Preoperative MOR and D2R availabilities were measured using PET with [11C]carfentanil and [11C]raclopride, respectively. Subject weight was recorded at 3, 6, 12, and 24 months after surgery. Radiotracer binding potentials (BPND) were extracted and correlated with patient weight at different time points. ROIs were delineated in the striatum and in limbic and paralimbic components of the emotion and reward networks. Results: MOR availabilities were not correlated with preoperative weight. MOR availabilities in the amygdala (r = -0.54), insula (r = -0.46), ventral striatum (r = -0.48) and putamen (r = -0.49) were associated with subject weight at 3 months. Significant association was found in the amygdala at 6 months (r = -0.53), 12 (r = -0.49), and 24 months (r = -0.50). D2R availabilities were associated with neither preoperative weight nor weight loss at any follow-up time point. Conclusions: To our knowledge, this is the first study to demonstrate that neuroreceptor markers prior to bariatric surgery in patients with morbid obesity are associated with the postoperative weight loss. Preoperative MOR availability in the amygdala was associated with long-term postoperative weight development after surgery suggesting that postoperative weight regain may derive from dysfunction in the opioid system. Postoperative weight loss outcomes after bariatric surgery may be partially predicted based on preoperative receptor availability opening up new potential for treatment possibilities.