title: Endogenous Opioid Mechanisms Are Implicated in Obesity and Weight Loss in Humans.
abstract: BACKGROUND
  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 μ-opioid receptor (MOR) system involvement in eating behaviors and their relationship to long-term maintenance of weight loss.
  
  
  METHODS
  This was a case-control study with follow-up of the treatment group at 1 year after intervention.
  
  
  METHODS
  The study was conducted at a tertiary care university medical center.
  
  
  METHODS
  Lean healthy (n = 7) and chronically obese (n = 7) men matched for age and ethnicity participated in the study.
  
  
  METHODS
  MOR availability measures were acquired with positron emission tomography and [(11)C]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.
  
  
  METHODS
  Brain MOR availability 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.
authors.affiliation: Departments of Psychiatry (P.R.B., J.-K.Z.), Radiology (J.-K.Z.), and Internal Medicine (A.E.R., C.F.B.), and Molecular and Behavioral Neuroscience Institute (K.E.D., J.-K.Z.), University of Michigan, Ann Arbor, Michigan 48109; and Department of Nutrition and Food Science (P.R.B.), Wayne State University, Detroit, Michigan 48202.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Burghardt
authors.affiliation: Departments of Psychiatry (P.R.B., J.-K.Z.), Radiology (J.-K.Z.), and Internal Medicine (A.E.R., C.F.B.), and Molecular and Behavioral Neuroscience Institute (K.E.D., J.-K.Z.), University of Michigan, Ann Arbor, Michigan 48109; and Department of Nutrition and Food Science (P.R.B.), Wayne State University, Detroit, Michigan 48202.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Rothberg
authors.affiliation: Departments of Psychiatry (P.R.B., J.-K.Z.), Radiology (J.-K.Z.), and Internal Medicine (A.E.R., C.F.B.), and Molecular and Behavioral Neuroscience Institute (K.E.D., J.-K.Z.), University of Michigan, Ann Arbor, Michigan 48109; and Department of Nutrition and Food Science (P.R.B.), Wayne State University, Detroit, Michigan 48202.
authors.forename: Kate E
authors.initials: KE
authors.lastname: Dykhuis
authors.affiliation: Departments of Psychiatry (P.R.B., J.-K.Z.), Radiology (J.-K.Z.), and Internal Medicine (A.E.R., C.F.B.), and Molecular and Behavioral Neuroscience Institute (K.E.D., J.-K.Z.), University of Michigan, Ann Arbor, Michigan 48109; and Department of Nutrition and Food Science (P.R.B.), Wayne State University, Detroit, Michigan 48202.
authors.forename: Charles F
authors.initials: CF
authors.lastname: Burant
authors.affiliation: Departments of Psychiatry (P.R.B., J.-K.Z.), Radiology (J.-K.Z.), and Internal Medicine (A.E.R., C.F.B.), and Molecular and Behavioral Neuroscience Institute (K.E.D., J.-K.Z.), University of Michigan, Ann Arbor, Michigan 48109; and Department of Nutrition and Food Science (P.R.B.), Wayne State University, Detroit, Michigan 48202.
authors.forename: Jon-Kar
authors.initials: JK
authors.lastname: Zubieta
mesh_terms: D000328:Adult; D001921:Brain / Q000378:metabolism; D031204:Caloric Restriction; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D016022:Case-Control Studies; D004435:Eating / Q000502:physiology; D005215:Fasting / Q000378:metabolism; D005283:Fentanyl / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging / Q000379:methods; D009765:Obesity / Q000378:metabolism*; D049268:Positron-Emission Tomography; D017450:Receptors, Opioid, mu / Q000378:metabolism / Q000502:physiology*; D015431:Weight Loss / Q000502:physiology*
chemical_list: D002250:Carbon Radioisotopes; D017450:Receptors, Opioid, mu; C017114:carfentanil; D005283:Fentanyl