Sex differences in serotonin–hypothalamic connections underpin a diminished sense of emotional well-being with increasing body weight

Background/Objectives: The neurobiological mechanisms linking obesity to emotional distress related to weight remain largely unknown. Participants/Methods: Here we combined positron emission tomography, using the serotonin transporter (5-HTT) radiotracer [11C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile, with functional connectivity magnetic resonance imaging, the Beck Depression Inventory (BDI-II) and the Impact of Weight on Quality of Life–Lite questionnaire (IWQOL-Lite) to investigate the role of central serotonin in the severity of depression (BDI-II), as well as in the loss of emotional well-being with body weight (IWQOL-Lite). Results: In a group of lean to morbidly obese individuals (n=28), we found sex differences in the 5-HTT availability-related connectivity of the hypothalamus. Males (n=11) presented a strengthened connectivity to the lateral orbitofrontal cortex, whereas in females (n=17) we found strengethened projections to the ventral striatum. Both regions are known as reward regions involved in mediating the emotional response to food. Their resting-state activity correlated positively to the body mass index (BMI) and IWQOL-Lite scores, suggesting that each region in both sexes also underpins a diminished sense of emotional well-being with body weight. Contrarily to males, we found that in females also the BDI-II positively correlated with the BMI and by trend with the activity in ventral striatum, suggesting that in females an increased body weight may convey to other mood dimensions than those weight-related ones included in the IWQOL-Lite. Conclusions: This study suggests sex differences in serotonin–hypothalamic connections to brain regions of the reward circuitry underpinning a diminished sense of emotional well-being with an increasing body weight

The central nervous norepinephrine network links a diminished sense of emotional well-being to an increased body weight

Objectives: The neurobiological mechanisms linking obesity to emotional distress remain largely undiscovered. Methods: In this pilot study, we combined positron emission tomography, using the norepinephrine transporter (NET) tracer [11C]-O-methylreboxetine, with functional connectivity magnetic resonance imaging, the Beck depression inventory (BDI), and the impact of weight on quality of life–Lite questionnaire (IWQOL–Lite), to investigate the role of norepinephrine in the severity of depression (BDI), as well as in the loss of emotional well-being with body weight (IWQOL–Lite). Results: In a small group of lean-to-morbidly obese individuals (n=20), we show that an increased body mass index (BMI) is related to a lowered NET availability within the hypothalamus, known as the brain’s homeostatic control site. The hypothalamus displayed a strengthened connectivity in relation to the individual hypothalamic NET availability to the anterior insula/frontal operculum, as well as the medial orbitofrontal cortex, assumed to host the primary and secondary gustatory cortex, respectively (n=19). The resting-state activity in these two regions was correlated positively to the BMI and IWQOL–Lite scores, but not to the BDI, suggesting that the higher the resting-state activity in these regions, and hence the higher the BMI, the stronger the negative impact of the body weight on the individual’s emotional well-being was. Conclusions: This pilot study suggests that the loss in emotional well-being with weight is embedded within the central norepinephrine network

Obesity: An addiction? Imaging of neurotransmitter systems in obesity

The brain is important in the regulation of eating behavior and satiety signaling. There is also evidence that many neurotransmitters are involved in food intake regulation and eating behavior; consequently dysregulated neurotransmitter systems may be involved in the pathophysiology of obesity. This chapter presents an overview of results of neurotransmitter imaging studies in obese humans. Presently, the dopaminergic, serotonergic, noradrenergic, opioid and cannabinoid systems have been studied with molecular imaging techniques in obese humans. The major findings are increased serotonin (5-hydroxytryptamine; 5-HT) 5-HT2A receptor availability in cortical regions, a complex relationship between dopamine D2/3 receptor (DRD2/3) availability and body mass index (BMI), probably an important role of the striatal and extra-striatal mu opioid receptor, and a possible role of the cannabinoid type 1 (CB1) receptor. There is no disturbance in serotonin transporter (SERT) availability in the thalamus and midbrain or in striatal dopamine transporter (DAT) availability. The effects of bariatric surgery on neurotransmission and findings in subgroups such as patients with binge eating disorder or insulin resistance are also discussed