Central serotonin transporter availability in highly obese individuals compared with non-obese controls: A [11C] DASB positron emission tomography study

Hesse, Swen; Rullmann, Michael; Luthardt, Julia; Winter, Karsten; Hankir, Mohammed K.; Becker, Georg-Alexander; Zientek, Franziska; Reissig, G; Regenthal, Ralf; Drabe, Mandy; Schinke, Christian; Bresch, Anke; Arélin, Katrin; Lobsien, Donald; Patt, Marianne; Meyer, Philipp; Faßhauer, Mathias; Fenske, Wiebke; Blüher, Matthias; Stümvoll, Michael; Sabri, Osama

doi:10.1007/s00259-015-3243-y

Cited by 24 publications

(34 citation statements)

References 27 publications

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“…Furthermore, LDA based on the NAT-rich LC revealed a relatively high power to distinguish obese from non-obese humans. Together with this, correlative analyses point towards a distinctive regional distribution of NAT availability between obese and non-obese individuals with more robust associations in obese individuals as we have found also for serotonin transporters [26]. This observational finding should be discussed with other parameters of neural connectivity in the near future to obtain specific group characteristics.…”

Section: Discussionsupporting

confidence: 68%

Central noradrenaline transporter availability in highly obese, non-depressed individuals

Hesse

Becker

Rullmann

et al. 2017

Eur J Nucl Med Mol Imaging

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Purpose The brain noradrenaline (NA) system plays an important role in the central nervous control of energy balance and is thus implicated in the pathogenesis of obesity. The specific processes modulated by this neurotransmitter which lead to obesity and overeating are still a matter of debate. Methods We tested the hypothesis that in vivo NA transporter (NAT) availability is changed in obesity by using positron emission tomography (PET) and S, S-[11C]O-methylreboxetine (MRB) in twenty subjects comprising ten highly obese (body mass index BMI > 35 kg/m2), metabolically healthy, non-depressed individuals and ten non-obese (BMI < 30 kg/m2) healthy controls. Results Overall, we found no significant differences in binding potential (BPND) values between obese and non-obese individuals in the investigated brain regions, including the NAT-rich thalamus (0.40 ± 0.14 vs. 0.41 ± 0.18; p = 0.84) though additional discriminant analysis correctly identified individual group affiliation based on regional BPND in all but one (control) case. Furthermore, inter-regional correlation analyses indicated different BPND patterns between both groups but this did not survive testing for multiple comparions. Conclusions Our data do not find an overall involvement of NAT changes in human obesity. However, preliminary secondary findings of distinct regional and associative patterns warrant further investigation.

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Section: Discussionsupporting

confidence: 68%

Central noradrenaline transporter availability in highly obese, non-depressed individuals

Hesse

Becker

Rullmann

et al. 2017

Eur J Nucl Med Mol Imaging

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“…First, the majority of our subjects were premenopausal women and our results remain to be validated in different age groups. Second, we studied men and women, while gender differences have been observed for striatal DAT [51] and diencephalic SERT binding [52], but not for hypothalamic SERT binding [31]. However, analyses of our results on SERT and DAT did not change after excluding the male subjects.…”

Section: Discussionmentioning

confidence: 97%

“…Previous imaging studies showed a negative correlation between BMI and diencephalic SERT binding in some [6] but not all [29, 30, 31] studies, and data on insulin sensitivity were not reported.…”

Section: Discussionmentioning

confidence: 99%

Serotonin Transporter Binding in the Diencephalon Is Reduced in Insulin-Resistant Obese Humans

Versteeg

Koopman²,

Booij

et al. 2016

Neuroendocrinology

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Background: Altered brain dopaminergic and serotonergic pathways have been shown in obese rodents and humans, but it is unknown whether this is related to obesity per se or to the metabolic derangements associated with obesity. Methods: We performed a case-control study in insulin-sensitive obese (ISO) and insulin-resistant obese (IRO) subjects (n = 12) and age-matched lean controls (n = 8) and measured serotonin transporter (SERT) binding in the whole diencephalon and specifically in the hypothalamus, as well as dopamine transporter (DAT) binding in the striatum using ¹²³I- FP-CIT single-photon emission computed tomography. We assessed insulin sensitivity using the homeostatic model assessment of insulin resistance. Results: BMI did not differ between the IRO and ISO subjects. SERT binding in the diencephalon was significantly lower in IRO than in ISO subjects, but was not different between lean and obese subjects. SERT binding in the hypothalamus tended to be reduced in obese versus lean subjects, but was not different between IRO and ISO subjects. Striatal DAT binding was similar between lean and obese subjects as well as between ISO and IRO subjects. Conclusions: We conclude that SERT binding in the diencephalon is reduced in insulin-resistant subjects independently of body weight, while hypothalamic SERT binding tends to be lower in obesity, with no difference between insulin-resistant and insulin-sensitive subjects. This suggests that the metabolic perturbations associated with obesity independently affect SERT binding within the diencephalon.

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“…The same brain regions reflecting tryptophan fluctuation and fat mass in our findings supported the findings above, suggesting the modulating role of body composition in serotonergic neurotransmission, or even the dysregulation of serotonergic system as a probable pathophysiologic mechanism in obesity. However, in another two studies the SERT availability showed no significant or negative association between non-obese and obsess subjects [47,49], which may implicate the lower reliability of the parameter BMI in predicting serotonergic system and risk decision behaviors. 1 6 In our study, we investigated only normal weight male participants without insulin resistant.…”

Section: Discussionmentioning

confidence: 87%

“…Previous studies using positron emission tomography (PET) or single-photon emission computed tomography (SPECT) suggested associations between body mass and 5-HT receptors density or transporter (SERT) availability in broad cortical regions (i.e., OFC, DLPFC, parietal lobule,) and subcortical regions (i.e., striatum and thalamus) [46][47][48][49]. Across normal-weight and obese people, positive correlations have been demonstrated between BMI, and global brain SERT availability, 5-HT 2A receptor binding across cerebral cortex, 5-HT 4 receptor binding in reward circuits [46,48,49].…”

Section: Discussionmentioning

confidence: 99%

Eating to dare - Nutrition impacts human risky decision and related brain function

Liu

Artigas

Ulrich

et al. 2020

Preprint

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Macronutrient composition modulates plasma amino acids that are precursors of neurotransmitters and can impact brain function and decisions. Neurotransmitter serotonin has been shown to regulate not only food-intake, but also economic decisions. We investigated whether an acute nutrition-manipulation inducing plasma tryptophan fluctuation affects brain function, thereby manipulating risk-decisions.Breakfasts differing in carbohydrate/protein ratios were offered to test changes in risk decision-making while metabolic and neural dynamics were tracked. We identified that a high-carb/protein meal increased plasma tryptophan which precisely predicted individual risk-shift. Critically, the link between plasma tryptophan and risk-shift depended on individual's fat-mass. Using fMRI, we further identified activation in the inferior parietal lobule during risk, of which activities 1) were sensitive to tryptophan fluctuation, 2) were modulated by individual's body fat mass and 3) further predicted the risk-shift in decision-making. Our results provide evidence for a personalized nutrition-driven-modulation on human risk-decision and its metabolic and neural mechanisms.

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Central serotonin transporter availability in highly obese individuals compared with non-obese controls: A [11C] DASB positron emission tomography study

Cited by 24 publications

References 27 publications

Central noradrenaline transporter availability in highly obese, non-depressed individuals

Central noradrenaline transporter availability in highly obese, non-depressed individuals

Serotonin Transporter Binding in the Diencephalon Is Reduced in Insulin-Resistant Obese Humans

Eating to dare - Nutrition impacts human risky decision and related brain function

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