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

Abstract

There is significant evidence linking a 'reward deficiency syndrome' (RDS), comprising decreased availability of striatal dopamine D2-like receptors (DD2lR) and addiction-like behaviors underlying substance use disorders and obesity. Regarding obesity, a systematic review of the literature with a meta-analysis of such data is lacking. Following a systematic review of the literature, we performed random-effects meta-analyses to determine group differences in case-control studies comparing DD2lR between individuals with obesity and non-obese controls and prospective studies of pre- to post-bariatric surgery DD2lR changes. Cohen's d was used to measure effect size. Additionally, we explored factors potentially associated with group differences in DD2lR availability, such as obesity severity, using univariate meta-regression. In a meta-analysis including positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies, striatal DD2lR availability did not significantly differ between obesity and controls. However, in studies comprising patients with class III obesity or higher, group differences were significant, favoring lower DD2lR availability in the obesity group. This effect of obesity severity was corroborated by meta-regressions showing inverse associations between the body mass index (BMI) of the obesity group and DD2lR availability. Post-bariatric changes in DD2lR availability were not found, although a limited number of studies were included in this meta-analysis. These results support lower DD2lR in higher classes of obesity which is a more targeted population to explore unanswered questions regarding the RDS.

Figure 1

Article selection flowchart. We performed a systematic review according to PRISMA guidelines, and from an initial pool of 840 titles, 17 articles were eligible for qualitative analysis, of which 13 were included in the meta-analysis. These included ten case–control studies comprising obesity and control groups and three prospective cohort studies of patients with obesity assessed before and after bariatric surgery. Of the prospective studies, one study also comprised a control group at baseline, and thus the data was included in case–control studies. Abbreviations: DD2lR—striatal dopamine D2-like receptor; BP—Binding Potential; ROI—Region of Interest.

Figure 2

Striatal dopamine D2-like receptor availability random-effects meta-analysis in obesity and healthy controls. A pooled meta-analysis of PET and SPECT studies showed that the availability of striatal dopamine D2-like receptor (DD2lR) did not differ between the obesity and control groups. Notes: Studies are organized according to scanner type—positron emission tomography (PET—lighter blue) or single-photon emission computed tomography (SPECT—darker blue). Within scanner type, studies are ranked from highest to lowest mean body mass index (BMI) of the obesity group. Studies in black writing comprise obesity groups with class III obesity or higher, while those in grey/blue comprise class I—II obesity.

Figure 3

Striatal dopamine D2-like receptor availability random-effects meta-analysis in obesity and healthy controls according to classes of obesity. Meta-analysis of striatal dopamine D2-like receptor (DD2lR) availability in individuals with obesity and controls showed significant group differences favoring lower striatal DD2lR in the obesity group when only studies comprising class III obesity or higher were analyzed (Fig. 3a). No differences were found in a meta-analysis of studies that included class I-II obesity (Fig. 3b). Notes: Studies are organized according to scanner type—positron emission tomography (PET—lighter blue) or single-photon emission computed tomography (SPECT—darker blue). Within scanner type, studies range from the highest to lowest mean body mass index (BMI) of the obesity group. Class III obesity or higher: BMI ≥ 40 kg/m²; Class I-II obesity: BMI from 30 to < 40 kg/m².

Figure 4

Univariate meta-regression of the association between striatal dopamine D2-like receptor availability and obesity level. An increasing body mass index (BMI) of the obesity group was significantly associated with striatal dopamine D2-like (DD2lR) availability favoring lower values in the obesity group (Fig. 4a). Accordingly, a higher BMI difference between the obesity and control groups (ΔBMI) was significantly associated with DD2lR availability, favoring lower values in the obesity group (Fig. 4b).

Figure 5

Striatal dopamine D2-like receptor availability random-effects meta-analysis after bariatric surgery. This analysis did not show changes in striatal DD2lR availability from pre- to post-bariatric surgery.