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

Previously, we have shown that in the opposite extremes of nutritional stat us (obesity and anorexia nervosa [AN]), the growth hormone IGH) 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 signif icantly increased (known as the "paradoxical response"). An opiate antagoni st infusion (naloxone [NAL]) inhibited this postprandial meal-induced augme nting effect in obese subjects, suggesting opioid involvement in the parado xical 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 t ested a group of patients, before and after BPD, composed of 10 females, ag ed 23 to 54 years, who after surgery had experienced a significant reductio n 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 mug/kg as an intravenous [IV] bolus) at 1:00 PM, in the fasting state; GHRH (1 mug/kg) at 1:00 PM, 45 minutes after a st andard 800-kcal meal consumed between noon and 12:15 PM; and fasting state and postprandial GHRH (I mug/kg) during NAL infusion (1.6 mg/h x 2.5 h, sta rting at noon). We found that NAL inhibited the paradoxical postprandial GH increase only in pre-BPD subjects (GH area under the concentration time cu rve [AUC] in (mug/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, afte r NAL + GHRH 156.17 +/- 24.96. On the other hand, NAL failed to have signif icant effects in post-BPD subjects (GH AUC in mug/L/90 min)-before meal: af ter GHRH 871.11 +/- 256.38, after NAL + GHRH 449.19 +/- 919.13; after meal: after GHRH 1,981.54 +/- 319.92, after NAL + GHRH 1,665.91 +/- 315.4. It co uld be hypothesized that the opioid system is radically modified by the sur gical procedure, and that opioids are not the only mediators in the paradox ical response, which persists after BPD, despite the reversion of the hypos ecretory GH state, which is a characteristic of obese subjects. Copyright ( C) 2001 by W.B. Saunders Company.