Molecular Imaging of Central Dopamine in Obesity: A Qualitative Review across Substrates and Radiotracers

Abstract

Dopamine is a neurotransmitter that plays a crucial role in adaptive behavior. A wealth of studies suggests obesity-related alterations in the central dopamine system. The most direct evidence for such differences in humans comes from molecular neuroimaging studies using positron emission tomography (PET) and single-photon emission computed tomography (SPECT). The aim of the current review is to give a comprehensive overview of molecular neuroimaging studies that investigated the relation between BMI or weight status and any dopamine target in the striatal and midbrain regions of the human brain. A structured literature search was performed and a summary of the extracted findings are presented for each of the four available domains: (1) D2/D3 receptors, (2) dopamine release, (3) dopamine synthesis, and (4) dopamine transporters. Recent proposals of a nonlinear relationship between severity of obesity and dopamine imbalances are described while integrating findings within and across domains, after which limitations of the review are discussed. We conclude that despite many observed associations between obesity and substrates of the dopamine system in humans, it is unlikely that obesity can be traced back to a single dopaminergic cause or consequence. For effective personalized prevention and treatment of obesity, it will be crucial to identify possible dopamine (and non-dopamine) profiles and their functional characteristics.

Striatal dopamine D2-like receptors availability in obesity and its modulation by bariatric surgery: a systematic review and meta-analysis

“…Indeed, we propose that future PET/SPECT studies should aim to characterize and select participants in further detail, including metabolically and behaviorally. Additionally, multi-radiopharmaceutical studies to assess, for example, striatal receptor availability and dopamine synthesis capacity in the same individuals, ideally in larger samples with a wider BMI range, can provide useful information 67 . Despite the obvious gaps that exist in the field, the results reported here corroborate brain changes in obesity, that may contribute to behavioral factors such as poor compliance to diet and exercise.…”

“…Although our findings suggest that central dopaminergic changes are more relevant for higher obesity classes, it is unlikely that obesity, and even severe obesity, can be translated into a single dopamine-related determinant. www.nature.com/scientificreports/ Within the dopamine system, nuclear medicine studies have typically targeted a single substrate, cross-sectionally, in small samples 67 . Nevertheless, this approach is not in line with the intricacy of obesity nor of dopaminergic physiology 67 .…”

Distinct adaptations of endocrine and cognitive functions may contribute to high variability in long-term weight loss outcome after bariatric surgery

“…In the future, imaging studies targeting reward-related brain correlates, cognitive paradigms during functional magnetic resonance imaging or with PET radiotracer imaging could reveal more direct evidence for postoperative alterations in dopamine signaling [108]. Prospectively, dopamine-related targets might be of relevance for developing pharmacological therapies in obesity treatment [109].…”

The interplay between prolactin and cardiovascular disease

“…Molecular imaging studies showed structural dopamine alterations in human obesity, especially lower dopamine D2/D3 receptor expression in striatal regions in extreme obesity (128,129). In contrast to Wang and colleagues (130), most studies show no linear correlation between BMI and D2/D3 receptor binding potential (131).For mild to severe obesity, the evidence points towards higher striatal D2/D3 receptor binding potential, although the picture is less clear (132). Animal studies have found that insulin interacts with dopamine in the VTA and striatum (133) and the administration of insulin directly into the VTA suppresses ingestive behavior (133).…”