Opioid dysregulation after biliopancreatic diversion: Effect of naloxone on preprandial and postprandial growth hormone (GH)-releasing hormone-induced GH release in surgically induced weight loss

Abstract

Previously, we have shown that in the opposite extremes of nutritional status (obesity and anorexia nervosa [AN]), the growth hormone (GH) response to GH-releasing hormone (GHRH) is not inhibited by the ingestion of a normal 800-kcal meal at noon. In obese subjects, GHRH-induced GH release is significantly increased (known as the “paradoxical response”). An opiate antagonist infusion (naloxone [NAL]) inhibited this postprandial meal-induced augmenting effect in obese subjects, suggesting opioid involvement in the paradoxical response. The paradoxical postprandial GH release persisted in obese subjects, who after biliopancreatic diversion (BPD) experienced a reduction in body weight, despite the elevation of fasting GH levels. We therefore tested a group of patients, before and after BPD, composed of 10 females, aged 23 to 54 years, who after surgery had experienced a significant reduction in body weight (mean body mass index [BMI], 25.78 ± 1.01 kg/mg v 44.68 ± 1.73 kg/mg). The subjects were studied 16 to 24 months after operation, in a phase of stabilized body weight. They underwent, in randomized order, the following tests: GHRH (1 μg/kg as an intravenous [IV] bolus) at 1:00 PM, in the fasting state; GHRH (1 μg/kg) at 1:00 PM, 45 minutes after a standard 800-kcal meal consumed between noon and 12:15 PM; and fasting state and postprandial GHRH (1 μg/kg) during NAL infusion (1.6 mg/h × 2.5 h, starting at noon). We found that NAL inhibited the paradoxical postprandial GH increase only in pre-BPD subjects (GH area under the concentration time curve [AUC] in μg/L/90 min)—before meal: after GHRH 237.54 ± 62.28, after NAL + GHRH 699.2 ± 271.57; after meal: after GHRH 575.46 ± 109.68, after NAL + GHRH 156.17 ± 24.96. On the other hand, NAL failed to have significant effects in post-BPD subjects (GH AUC in μg/L/90 min)—before meal: after GHRH 871.11 ± 256.38, after NAL + GHRH 449.19 ± 119.13; after meal: after GHRH 1,981.54 ± 319.92, after NAL + GHRH 1,665.91 ± 315.4. It could be hypothesized that the opioid system is radically modified by the surgical procedure, and that opioids are not the only mediators in the paradoxical response, which persists after BPD, despite the reversion of the hyposecretory GH state, which is a characteristic of obese subjects.