Central noradrenaline transporter availability in highly obese, non-depressed individuals

Abstract

Purpose The brain noradrenaline (NA) system plays an important role in the central nervous control of energy balance and is thus implicated in the pathogenesis of obesity. The specific processes modulated by this neurotransmitter which lead to obesity and overeating are still a matter of debate. Methods We tested the hypothesis that in vivo NA transporter (NAT) availability is changed in obesity by using positron emission tomography (PET) and S, S-[11C]O-methylreboxetine (MRB) in twenty subjects comprising ten highly obese (body mass index BMI > 35 kg/m2), metabolically healthy, non-depressed individuals and ten non-obese (BMI < 30 kg/m2) healthy controls. Results Overall, we found no significant differences in binding potential (BPND) values between obese and non-obese individuals in the investigated brain regions, including the NAT-rich thalamus (0.40 ± 0.14 vs. 0.41 ± 0.18; p = 0.84) though additional discriminant analysis correctly identified individual group affiliation based on regional BPND in all but one (control) case. Furthermore, inter-regional correlation analyses indicated different BPND patterns between both groups but this did not survive testing for multiple comparions. Conclusions Our data do not find an overall involvement of NAT changes in human obesity. However, preliminary secondary findings of distinct regional and associative patterns warrant further investigation.

Changes of central noradrenaline transporter availability in immunotherapy-naïve multiple sclerosis patients

“…Although it is tempting to attribute NAT changes in MS specifically to the limbic system (amygdala, striatum) or brain regions essential for the regulation of vigilance and arousal (thalamus, brainstem), it must be noted that NAT tended to be higher in almost all brain regions of the patient cohort. However, some of the analysed regions such as the hippocampus or insula have low NAT availabilities, a poorer signal-to-noise ratio and high variability 19 ; hence, statistical power possibly was not sufficient to detect intergroup differences in all regions specificied in this small sample. Yet, exploratory analyses of these brain regions are of interest since they belong to noradrenergic circuits which are involved in emotion regulation and memory processing 5,47,48 .…”

“…We used a 10-min transmission scan (from three 68 Ga sources), which was performed prior to the emission scan, for attenuation correction. An iterative reconstruction (10 iterations, 16 subsets) was applied to a transverse image series (63 slices, 128 × 128 matrix, voxel size 2.6 × 2.6 × 2.4 mm 3 ) with a Hann filter (cut-off 4.9 mm) for post-processing 19 .…”

“…The kinetic modelling yields estimates of the BP ND independent of injected tracer dose and body weight. In the final computation of the DVR, the population mean value of k2′ in the thalamus from 17 study participants (described in detail in Hesse et al 19 ) was 0.0238 ± 0.008 1/min and used as fixed washout constant k2′_fix. MRTM2 becomes linear after a certain time, called t* 57 .…”

“…To assess central NAT availability in vivo, PET was applied using the highly selective radiotracer (S,S)-[ 11 C]O-methylreboxetine ([ 11 C]MRB) 19 , 20 . We expected ( i ) changes of central NAT availability in immunotherapy-naïve MS patients compared to healthy controls (HC) and explored ( ii ) whether there is an association of NAT with physical disability, time since manifestation and psychometric measures of fatigue and depressive symptoms in MS patients.…”

PET imaging of noradrenaline transporters in Parkinson’s disease: focus on scan time

“…C-11 MRB was developed by Ding et al [ 14 , 15 ] for the exploration of NET availability in patients with psychiatric disorders [ 16 – 18 ]. The main practical limitation of C-11 MRB is the long scan duration; the published scanning protocols comprise dynamic PET scans over at least 90 min [ 11 , 17 , 18 ]. Long protocols, however, cause major discomfort for patients with PD, especially when pausing dopaminergic medication.…”