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      Comparison of brain serotonin transporter using [I-123]-ADAM between obese and non-obese young adults without an eating disorder

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          Abstract

          Cerebral serotonin metabolism has an important but controversial role in obesity. However, it is not given enough attention in morbidly obese young adults. We used single photon emission computed tomography (SPECT) with [I-123]-labeled 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine (ADAM) to investigate changes in serotonin transporter (SERT) availability in 10 morbidly obese young adults without an eating disorder (M/F = 5/5, body mass index (BMI): 40.3 ± 4.1 kg/m 2, percentage of body fat (BF%): 46.0 ± 3.9%) and 10 age- and sex-matched non-obese controls (BMI: 20.3 ± 1.2 kg/m 2, BF%: 20.6 ± 8.9%). All participants underwent SPECT at 10 min and 6 h after an injection of 200 MBq of [I-123]-ADAM. The SERT binding site (midbrain) was drawn with cerebellum normalization. The BF% and fat distribution were measured using dual-energy X-ray absorptiometry. The midbrain/cerebellum SERT binding ratios (2.49 ± 0.46 vs. 2.47 ± 0.47; p = 0.912) at 6 h were not significantly different between groups, nor was the distribution of the summed images at 10 min (1.36 ± 0.14 vs. 1.35 ± 0.11; p = 0.853). There were no significant correlations between midbrain/cerebellum SERT binding ratio and age, BMI, BF%, or fat distribution. No significant difference in SERT availability in the midbrain between morbidly obese and non-obese young adults without an eating disorder indicates an unmet need for investigating the role of cerebral serotonin in obesity.

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          The SCOFF questionnaire: assessment of a new screening tool for eating disorders.

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            Neuroimaging and obesity: current knowledge and future directions.

            Neuroimaging is becoming increasingly common in obesity research as investigators try to understand the neurological underpinnings of appetite and body weight in humans. Positron emission tomography (PET), functional magnetic resonance imaging (fMRI) and magnetic resonance imaging (MRI) studies examining responses to food intake and food cues, dopamine function and brain volume in lean vs. obese individuals are now beginning to coalesce in identifying irregularities in a range of regions implicated in reward (e.g. striatum, orbitofrontal cortex, insula), emotion and memory (e.g. amygdala, hippocampus), homeostatic regulation of intake (e.g. hypothalamus), sensory and motor processing (e.g. insula, precentral gyrus), and cognitive control and attention (e.g. prefrontal cortex, cingulate). Studies of weight change in children and adolescents, and those at high genetic risk for obesity, promise to illuminate causal processes. Studies examining specific eating behaviours (e.g. external eating, emotional eating, dietary restraint) are teaching us about the distinct neural networks that drive components of appetite, and contribute to the phenotype of body weight. Finally, innovative investigations of appetite-related hormones, including studies of abnormalities (e.g. leptin deficiency) and interventions (e.g. leptin replacement, bariatric surgery), are shedding light on the interactive relationship between gut and brain. The dynamic distributed vulnerability model of eating behaviour in obesity that we propose has scientific and practical implications. © 2011 The Authors. obesity reviews © 2011 International Association for the Study of Obesity.
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              Brain dopamine and obesity.

              The cerebral mechanisms underlying the behaviours that lead to pathological overeating and obesity are poorly understood. Dopamine, a neurotransmitter that modulates rewarding properties of food, is likely to be involved. To test the hypothesis that obese individuals have abnormalities in brain dopamine activity we measured the availability of dopamine D2 receptors in brain. Brain dopamine D2 receptor availability was measured with positron emission tomography (PET) and [C-11]raclopride (a radioligand for the dopamine D2 receptor). Bmax/Kd (ratio of the distribution volumes in striatum to that in cerebellum minus 1) was used as a measure of dopamine D2 receptor availability. Brain glucose metabolism was also assessed with 2-deoxy-2[18F]fluoro-D-glucose (FDG). Striatal dopamine D2 receptor availability was significantly lower in the ten obese individuals (2.47 [SD 0.36]) than in controls (2.99 [0.41]; p < or = 0.0075). In the obese individuals body mass index (BMI) correlated negatively with the measures of D2 receptors (r=0.84; p < or = 0.002); the individuals with the lowest D2 values had the largest BMI. By contrast, neither whole brain nor striatal metabolism differed between obese individuals and controls, indicating that striatal reductions in D2 receptors were not due to a systematic reduction in radiotracer delivery. The availability of dopamine D2 receptor was decreased in obese individuals in proportion to their BMI. Dopamine modulates motivation and reward circuits and hence dopamine deficiency in obese individuals may perpetuate pathological eating as a means to compensate for decreased activation of these circuits. Strategies aimed at improving dopamine function may be beneficial in the treatment of obese individuals.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                9 February 2017
                2017
                : 12
                : 2
                : e0170886
                Affiliations
                [1 ]Departments of Family Medicine, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan
                [2 ]Institutes of Behavioral Medicine, National Cheng Kung University College of Medicine, Tainan, Taiwan
                [3 ]Institutes of Gerontology, National Cheng Kung University College of Medicine, Tainan, Taiwan
                [4 ]Institutes of Clinical Medicine, National Cheng Kung University College of Medicine, Tainan, Taiwan
                [5 ]Departments of Psychiatry, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan
                [6 ]Institute of Nuclear Energy Research, Longtan Township, Taoyuan County, Taiwan
                [7 ]Departments of Nuclear Medicine, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan
                University of Barcelona, Faculty of Biology, SPAIN
                Author notes

                Competing Interests: All authors declare that they have no conflicts of interest.

                • Conceptualization: CHW WJY.

                • Data curation: CHW CSC LHS WJY.

                • Formal analysis: CHW WJY.

                • Funding acquisition: CHW WJY.

                • Investigation: CHW CSC WJY.

                • Methodology: CHW LHS WJY.

                • Project administration: CHW WJY.

                • Resources: CHW CSC LHS WJY.

                • Software: LHS WJY.

                • Supervision: WJY.

                • Validation: CSC YKY LHS.

                • Visualization: CHW CSC YKY WJY.

                • Writing – original draft: CHW.

                • Writing – review & editing: CHW CSC YKY LHS WJY.

                Article
                PONE-D-16-12406
                10.1371/journal.pone.0170886
                5300236
                28182708
                16f14e90-f829-4140-81a2-781b41eadf42
                © 2017 Wu et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 26 March 2016
                : 12 January 2017
                Page count
                Figures: 1, Tables: 2, Pages: 10
                Funding
                Funded by: NSC
                Award ID: 93-NU-7-006-003, 94-NU-7-006-004,93-2314-B-006-110, and 94-2314-B-006-119
                Award Recipient :
                Funding for this study was provided by Taiwan National Science Council (NSC) grants NSC93-NU-7-006-003, NSC94-NU-7-006-004, NSC93-2314-B-006-110, and NSC94-2314-B-006-119; the NSC had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
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