Marta Lapo Pais, Joana Crisóstomo, Antero Abrunhosa, Miguel Castelo-Branco
{"title":"PET/fMRI demonstrates that bariatric surgery may reverse striatal dopaminergic dysfunction in women with obesity.","authors":"Marta Lapo Pais, Joana Crisóstomo, Antero Abrunhosa, Miguel Castelo-Branco","doi":"10.1038/s43856-025-01079-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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 (BP<sub>ND</sub>) 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.</p><p><strong>Results: </strong>We find mean D2/3 R BP<sub>ND</sub> 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 BP<sub>ND</sub> 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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":"5 1","pages":"375"},"PeriodicalIF":5.4000,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12394448/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Communications medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1038/s43856-025-01079-z","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
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.