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Neuroimage. 2014 Feb 1;86:306-10. doi: 10.1016/j.neuroimage.2013.10.004. Epub 2013 Oct 10.

Decreased norepinephrine transporter availability in obesity: Positron Emission Tomography imaging with (S,S)-[(11)C]O-methylreboxetine.

Author information

1
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.
2
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.
3
Department of Diagnostic Radiology, Yale University, New Haven, CT, USA.
4
Department of Psychiatry, Yale University, New Haven, CT, USA.
5
Department of Psychiatry, Yale University, New Haven, CT, USA; Child Study Center, Yale University, New Haven, CT, USA.
6
Department of Diagnostic Radiology, Yale University, New Haven, CT, USA; Department of Psychiatry and Radiology, New York University, New York, NY, USA.
7
Department of Diagnostic Radiology, Yale University, New Haven, CT, USA; Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
8
Department of Psychiatry and Radiology, New York University, New York, NY, USA. Electronic address: Alexander.Neumeister@nyumc.org.

Abstract

OBJECTIVES:

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.

KEYWORDS:

BMI; Human; Norepinephrine; Obesity; PET; [(11)C]-MRB

PMID:
24121204
PMCID:
PMC3947246
DOI:
10.1016/j.neuroimage.2013.10.004
[Indexed for MEDLINE]
Free PMC Article
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