title: Decreased norepinephrine transporter availability in obesity: Positron Emission Tomography imaging with (S,S)-[(11)C]O-methylreboxetine.
abstract: OBJECTIVE
  Noradrenergic dysfunction is implicated in obesity. The norepinephrine transporter (NET) regulates the synaptic availability of norepinephrine. However, NET availability has not been previously characterized in vivo in obese people using Positron Emission Tomography (PET) imaging. Here we report findings evaluating NET availability in individuals with obesity and matched lean (i.e., normal weight) comparison subjects.
  
  
  METHODS
  Seventeen obese but otherwise healthy individuals with a mean±SD body mass index (BMI) of 34.7±2.6 and 17 lean individuals with a mean±SD BMI of 23.1±1.4 were studied using a high-resolution research tomograph (HRRT) and (S,S)-[(11)C]O-methylreboxetine ([(11)C]-MRB), a radioligand selective for the NET. The regional brain NET binding potential (BPND) was estimated by the multilinear reference tissue model 2 (MRTM2) with the occipital cortex as a reference region. BPND for regions of interest were obtained with the Automated Anatomic Labeling (AAL) template registered to individual's structural MR scans.
  
  
  RESULTS
  Obese individuals had lower NET BPND values in the thalamus (p<0.038, 27% reduction) including within the pulvinar (p<0.083, 30% reduction), but not in the hypothalamus, locus coeruleus or the raphe nuclei, compared to lean individuals. When age was included as a covariate, the difference in NET BPND values remained significant in the thalamus (p<0.025) and pulvinar (p<0.042).
  
  
  CONCLUSIONS
  These results indicate that NET availability is decreased in the thalamus, including the pulvinar, in obese individuals. These findings further support data indicating noradrenergic dysfunction in obesity and suggest impaired NE clearance in obesity.
authors.affiliation: Department of Psychiatry, Yale University, New Haven, CT, USA; Department of Neurobiology, Yale University, New Haven, CT, USA; Interdepartmental Neuroscience Program, Yale University, New Haven, CT, USA.
authors.forename: Chiang-shan R
authors.initials: CS
authors.lastname: Li
authors.affiliation: Department of Psychiatry, Yale University, New Haven, CT, USA; Department of Neurobiology, Yale University, New Haven, CT, USA; Child Study Center, Yale University, New Haven, CT, USA.
authors.forename: Marc N
authors.initials: MN
authors.lastname: Potenza
authors.affiliation: Department of Diagnostic Radiology, Yale University, New Haven, CT, USA.
authors.forename: Dianne E
authors.initials: DE
authors.lastname: Lee
authors.affiliation: Department of Diagnostic Radiology, Yale University, New Haven, CT, USA.
authors.forename: Beata
authors.initials: B
authors.lastname: Planeta
authors.affiliation: Department of Diagnostic Radiology, Yale University, New Haven, CT, USA.
authors.forename: Jean-Dominique
authors.initials: JD
authors.lastname: Gallezot
authors.affiliation: Department of Diagnostic Radiology, Yale University, New Haven, CT, USA.
authors.forename: David
authors.initials: D
authors.lastname: Labaree
authors.affiliation: Department of Psychiatry, Yale University, New Haven, CT, USA.
authors.forename: Shannan
authors.initials: S
authors.lastname: Henry
authors.affiliation: Department of Diagnostic Radiology, Yale University, New Haven, CT, USA.
authors.forename: Nabeel
authors.initials: N
authors.lastname: Nabulsi
authors.affiliation: Department of Psychiatry, Yale University, New Haven, CT, USA; Child Study Center, Yale University, New Haven, CT, USA.
authors.forename: Rajita
authors.initials: R
authors.lastname: Sinha
authors.affiliation: Department of Diagnostic Radiology, Yale University, New Haven, CT, USA; Department of Psychiatry and Radiology, New York University, New York, NY, USA.
authors.forename: Yu-Shin
authors.initials: YS
authors.lastname: Ding
authors.affiliation: Department of Diagnostic Radiology, Yale University, New Haven, CT, USA; Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
authors.affiliation: Department of Psychiatry and Radiology, New York University, New York, NY, USA. Electronic address: Alexander.Neumeister@nyumc.org.
authors.forename: Alexander
authors.initials: A
authors.lastname: Neumeister
mesh_terms: D000328:Adult; D001682:Biological Availability; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008297:Male; D009025:Morpholines / Q000493:pharmacokinetics*; D009638:Norepinephrine / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D000077593:Reboxetine; D013788:Thalamus / Q000000981:diagnostic imaging / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D002250:Carbon Radioisotopes; D009025:Morpholines; D050484:Norepinephrine Plasma Membrane Transport Proteins; C524178:O-methyl reboxetine; D019275:Radiopharmaceuticals; D000077593:Reboxetine; D009638:Norepinephrine
keywords: BMI; Human; Norepinephrine; Obesity; PET; [(11)C]-MRB