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. 2025 Aug 28;5(1):375.
doi: 10.1038/s43856-025-01079-z.

PET/fMRI demonstrates that bariatric surgery may reverse striatal dopaminergic dysfunction in women with obesity

Marta Lapo Pais  1   2   3 , Joana Crisóstomo  1   4 , Antero Abrunhosa  1   2 , Miguel Castelo-Branco  5   6   7
Affiliations

PET/fMRI demonstrates that bariatric surgery may reverse striatal dopaminergic dysfunction in women with obesity

Marta Lapo Pais et al. Commun Med (Lond). .

Abstract

Background: Central mechanisms may play a role in the success of bariatric surgery (BS), the treatment of choice for refractory obesity. We hypothesize that central dopaminergic receptor function in striatal brain regions is a pivotal mechanism in the success of BS.

Methods: We conducted a cross-sectional study to investigate central dopamine type 2 and 3 receptors (D2/3 R) within striatal brain regions in successful weight loss (WL) through BS. Positron Emission Tomography was used to map nondisplaceable binding potential (BPND) of D2/3 R in 48 women: 19 successful responders to BS, 12 with obesity (OB), and 17 normal-weight controls. Parametric maps were compared between-groups in regions of interest and at voxel-level. We also investigated brain blood oxygenation level-dependent (BOLD) responses to food content using functional Magnetic Resonance Imaging (fMRI) and how key variables correlate with D2/3 R binding.

Results: We find mean D2/3 R BPND significant differences between OB and controls in the ventral striatum (p = 0.042) and at voxel-level across striatum between OB and the other groups (p < 0.05). Food content (Food > Non-food, p = 0.05) reveals significantly higher neural activation in striatum also for OB compared to the other groups. Moreover, D2/3 R BPND values correlate with dysfunctional self-report measures of eating behaviors, incentive salience to food cue and high-calorie food preferences in obesity. Notably, BOLD responses (Food > Baseline) in striatum correlate positively with D2/3 R binding in ventral striatum.

Conclusions: Striatal dopaminergic dysfunction in obesity may enhance salience to food cues, driving cravings and compulsive eating. BS may reverse the striatal molecular and functional disruptions found in obesity.

Plain language summary

Bariatric surgery is a type of surgery that helps people with severe obesity lose weight. The success of this surgery may involve changes in the brain. This study investigated how these changes impact weight loss and eating behavior, focusing on dopamine, a brain chemical known to have an effect on pleasure, food cravings and eating behaviors. We used brain imaging to examine dopamine in women with successful weight loss after bariatric surgery, women with obesity, and normal weight women. We found that obesity is associated with changes in dopamine, which may contribute to food cravings and compulsive eating. Successful weight loss after bariatric surgery appear to reverse these changes. This work may help clarify how bariatric surgery promotes weight loss.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Clusters used in the fMRI analysis.
Clusters result from the intersection between the whole RFX GLM brain analysis (Food > Baseline, p-FDR = 0.001 for striatum [green] and p-FDR 0.05 for NAc [orange] and GPe [yellow]) and the anatomical boundaries of these regions. FDR false discovery rate; fMRI functional Magnetic Resonance Imaging; GLM general linear model; GPe external segment of the globus pallidum; NAc nucleus accumbens; RFX Random Effects Analysis.
Fig. 2
Fig. 2. Mean D2/3 R BPND [11C]raclopride PET images.
D2/3 R availability for each group: pBSsuccess (n = 19); OB (n = 12) and NW (n = 17). BPND non-displaceable binding potential; D2/3 R dopamine type 2 and 3 receptors; NW normal-weight women; OB women with obesity; pBSsuccess women who have successfully responded to bariatric surgery; PET Positron Emission Tomography.
Fig. 3
Fig. 3. ROI-based PET analysis.
Scatter plot (mean ± SD) showing the brain D2/3 R BPND values in three anatomical brain ROIs for each group: NW (n = 17) is depicted using gray rhombuses, OB (n = 11 for putamen and n = 12 for other ROIs) with orange triangles, and pBSsuccess (n = 19) with blue circles. BPND non-displaceable binding potential; D2/3 R dopamine type 2 and 3 receptors; NW normal-weight women; OB women with obesity; pBSsuccess women who have successfully responded to bariatric surgery; PET Positron Emission Tomography; ROIs regions of interest.
Fig. 4
Fig. 4. Voxel-based PET analysis.
F-Contrast —comparison of brain D2/3 R BPND between groups: pBSsuccess (n = 19); OB (n = 12) and NW (n = 17). Statistical analysis was performed using the FDR correction (p < 0.05) and an extent threshold of 226 voxels. BPND non-displaceable binding potential; D2/3 R dopamine type 2 and 3 receptors; FDR false discovery rate; PET Positron Emission Tomography.
Fig. 5
Fig. 5. Voxel-based PET analysis.
T-Contrasts —comparison of brain D2/3 R BPND between pBSsuccess (n = 19), OB (n = 12) and NW (n = 17) groups. Statistical analysis was performed using the FDR correction (p < 0.05) and an extent threshold of 522 voxels for OB > pBSsuccess and 489 for OB > NW. BPND non-displaceable binding potential; D2/3 R dopamine type 2 and 3 receptors; FDR false discovery rate; NW normal-weight women; OB women with obesity; pBSsuccess surgery; PET Positron Emission Tomography.
Fig. 6
Fig. 6. Whole-brain fMRI analysis.
Whole-brain RFX ANCOVA (Food > Non-Food, p = 0.05) revealing significantly higher activation within the striatum for the OB (n = 11) compared to the NW (n = 17) and pBSsuccess (n = 18) groups. ANCOVA analysis of covariance; NW normal-weight women; OB women with obesity; pBSsuccess women who have successfully responded to bariatric surgery; RFX Random Effects Analysis.
Fig. 7
Fig. 7. Association between BMI and vSTR (BPND).
Scatter plot showing the relationship between BMI and vSTR (BPND) for each group: NW (n = 17) is depicted using gray rhombuses, OB (n = 12) with orange triangles, and pBSsuccess (n = 19) with blue circles. BMI Body Mass Index; BPND non-displaceable binding potential; NW normal-weight women; OB women with obesity; pBSsuccess women who have successfully responded to bariatric surgery; vSTR ventral striatum.
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