Changes of insular norepinephrine transporters in highly obese individuals accompany weight-loss and changes in eating behaviour after 6 months dietary intervention

Objectives Neuroimaging studies have revealed structural and functional changes of the central norepinephrine system (NE) in brain regions associated both with obesity and neuromodulatory actions of the NE system that promote eating disorders. The therapeutic targets to suppress appetite and reduce weight for example by pharmacological intervention are the presynaptic NE transporters (NET). The mechanism, however, which relate NET activity with feeding remain unknown. The main goal of this study was to determine whether NET is a stable trait of human obesity or might be altered through treatment-as-usual, in particular dietary intervention, consequently results out of obesity. Therefore we compare cerebral PET data reflecting regional NET availability in highly obese individuals before and after 6 months of dietary intervention together with behavioral scores assessing emotional eating as well as impulsive and effort control (FEV-II, BIS-11, ATQ).

Methods 10 obese non-depressed volunteers (BMI>35; 42.4±3.7kg/m², age 34±9yrs, 4♀) underwent PET with the NET-selective (S,S)-[11C]O-methylreboxetine (MRB), MRI and BIS-11, FEV-II, ATQ before and 6 months after dietary intervention, applying atlas-derived volume-of-interest image analysis using a multi-linear reference tissue model to obtain NET binding potential (BPnd). NET availability in distinct brain areas from 10 obese patients were compared with those of 10 matched non-obese volunteers (BMI 23.9±2.5kg/m², age 33±10yrs, 4♀).

Results Neither significant BMI changes nor a correlation between changes in BMI with BPnd changes over time were found in the control group (delta-BMI -0.2±5.9%). In obese patients, change in BMI (-3.3±5.3%) was significantly correlated with the NET availability of the insula (R=-0.67, p=0.033) and of the hippocampus (R=-0.69, p=0.029) and increased in obese individuals following completion of intervention (e.g. insula delta BPnd 0.02±0.11). NET changes in the insula were related to changes in FEV-II (R=0.71; p=0.02), ATQ (R= -0.67; p=0.03) and BIS-11 total score (R=0.62; p=0.06). Furthermore we found a correlation between changes in the BMI with changes in these behavioral scales (BIS-11 total: R= 0.76; p= 0.01; FEV-II: R= 0.63; p= 0.05; ATQ: R= -0.77; p=0.009).

Conclusions During 6-months follow up of dietary intervention in highly obese individuals, NET changes predominantly in the insula indicate the involvement of sensory-interoceptive functions accompanying regimes for treating obesity. These changes are closely related to improvement in eating behaviors, which suggests a lower emotionally driven and less impulsive food intake and may point to a more balanced NE tone after successful treatment. However, BMI-related NET changes in the hippocampus did not have a behavioral correlate so far.