Endogenous Opioid Mechanisms Are Implicated in Obesity and Weight Loss in Humans

Context: Successful long-term weight loss is challenging. Brain endogenous opioid systems regulate associated processes; however, their role in the maintenance of weight loss has not been adequately explored in humans. Objective: In a preliminary study, the objective was to assess central mu-opioid receptor (MOR) system involvement in eating behaviors and their relationship to long-term maintenance of weight loss. Design: This was a case-control study with follow-up of the treatment group at 1 year after intervention. Setting: The study was conducted at a tertiary care university medical center. Participants: Lean healthy (n = 7) and chronically obese (n = 7) men matched for age and ethnicity participated in the study. Interventions: MOR availability measures were acquired with positron emission tomography and [C-11] carfentanil. Lean healthy men were scanned twice under both fasted and fed conditions. Obese men were placed on a very low-calorie diet to achieve 15% weight loss from baseline weight and underwent two positron emission tomography scans before and two after weight loss, incorporating both fasted and fed states. Main Outcome Measures: Brain MORavailability and activation were measured by reductions in MOR availability (nondisplaceable binding potential) from the fed compared with the fasted-state scans. Results: Baseline MOR nondisplaceable binding potential was reduced in obese compared with the lean and partially recovered obese after weight loss in regions that regulate homeostatic, hedonic, and emotional responses to feeding. Reductions in negative affect and feeding-induced MOR system activation in the right temporal pole were highly correlated in leans but not in obese men. A trend for an association between MOR activation in the right temporal pole before weight loss and weight regain 1 year was found. Conclusions: Although these preliminary studies have a small sample size, these results suggest that obesity and diet-induced weight loss impact central MOR binding and endogenous opioid system function. MOR system activation in response to an acute meal may be related to the risk of weight regain.