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

Wu, Chih Hsing; Chang, Chin Sung; Yang, Yen Kuang; Shen, Lie; Yao, Wei Jen

doi:10.1371/journal.pone.0170886

Cited by 11 publications

(9 citation statements)

References 47 publications

(66 reference statements)

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“…Similarly to obese high-5HT rats, rodents with genetic deletion of 5HTT have elevated extracellular 5HT levels and tissue 5HIAA/5HT ratios, but findings regarding their obese phenotype are inconsistent (Kim et al, 2005;Homberg et al, 2007;Murphy and Lesch, 2008;Homberg et al, 2010;Zha et al, 2017). Further, human neuroimaging studies support both increase and decrease, as well as no change in intrasynaptic 5HT level in obesity (Koskela et al, 2008;Erritzoe et al, 2010;Hesse et al, 2016;Wu et al, 2017;van Galen et al, 2018). Interestingly, while in morbid obesity no changes in 5HTT binding were observed, moderately obese subjects showed increased 5HTT-binding potential in comparison to lean controls (Koskela et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Constitutionally High Serotonin Tone Favors Obesity: Study on Rat Sublines With Altered Serotonin Homeostasis

et al. 2020

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Central and peripheral pools of biogenic monoamine serotonin (5-hydroxytryptamine [5HT]) exert opposite effects on the body weight regulation: increase in brain 5HT activity is expected to decrease body weight, whereas increase in peripheral 5HT activity will increase body weight and adiposity. In a genetic model of rats with constitutionally highor low-5HT homeostasis (hyperserotonergic/hyposerotonergic rats), we have studied how individual differences in endogenous 5HT tone modulate net energy balance of the organism. The high-5HT and low-5HT sublines of the model were developed by selective breeding toward extreme platelet activities of 5HT transporter, a key molecule determining 5HT bioavailability/activity. In animals from high-5HT and low-5HT sublines, we assessed physiological characteristics associated with body weight homeostasis and expression profile of a large scale of body weight-regulating genes in hypothalamus, a major brain region controlling energy balance. Results showed that under standard chow diet animals from the high-5HT subline, as compared to low-5HT animals, have lifelong increased body weight (by 12%), higher absolute daily food intake (by 9%), and different pattern of fat distribution (larger amount of white adipose tissue and lower amount of brown adipose tissue). A large number of body weight-regulating hypothalamic genes were analyzed for their mRNA expression: 24 genes by reverse transcription-quantitative polymerase chain reaction (n = 9-10 rats/subline) including neuropeptides and their receptors, growth factors, transcriptional factors, and receptors for peripheral signals, and a total of 84 genes of various classes by polymerase chain reaction array (pools of six rats/subline). Only few genes showed significant differences in mRNA expression levels between 5HT sublines (e.g. neuropeptide Y receptor, fibroblast growth factor 10), but high-5HT animals displayed a clear trend to upregulation of mRNAs for a number of orexigenic signaling peptides, their receptors, and other molecules with orexigenic activity. Receptors for peripheral signals (leptin, insulin) and molecules in their downstream signaling were not altered, indicating no changes in central insulin/leptin resistance. At the protein level, there were no differences in the Frontiers in Neuroscience | www.frontiersin.org 1 March 2020 | Volume 14 | Article 219 Kesić et al. Serotonin and Body Weight Regulationcontent of hypothalamic leptin receptor between 5HT sublines, but significant sex and age effects were observed. Results show that higher constitutive/individual 5HT tone favors higher body weight and adiposity probably due to concurrent upregulation of several hypothalamic orexigenic pathways.

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Section: Discussionmentioning

confidence: 99%

Constitutionally High Serotonin Tone Favors Obesity: Study on Rat Sublines With Altered Serotonin Homeostasis

et al. 2020

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“…In addition, women with obesity have lower levels of serotonin and its metabolites in CSF compared with lean women 159 . Interestingly, studies measuring serotonin receptor or SERT availability using either PET or SPECT consistently support decreased serotonin levels/signaling in a variety of brain regions in individuals with obesity 58,160–164 …”

Section: Disturbed Serotonergic Signaling In Obesity and Therapeutic Implicationsmentioning

confidence: 99%

Serotonin, food intake, and obesity

2021

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Summary The role of serotonin in food intake has been studied for decades. Food intake is mainly regulated by two brain circuitries: (i) the homeostatic circuitry, which matches energy intake to energy expenditure, and (ii) the hedonic circuitry, which is involved in rewarding and motivational aspects of energy consumption. In the homeostatic circuitry, serotonergic signaling contributes to the integration of metabolic signals that convey the body's energy status and facilitates the ability to suppress food intake when homeostatic needs have been met. In the hedonic circuitry, serotonergic signaling may reduce reward‐related, motivational food consumption. In contrast, peripherally acting serotonin promotes energy absorption and storage. Disturbed serotonergic signaling is associated with obesity, emphasizing the importance to understand the role of serotonergic signaling in food intake. However, unraveling the serotonin‐mediated regulation of food intake is complex, as the effects of serotonergic signaling in different brain regions depend on the regional expression of serotonin receptor subtypes and downstream effects via connections to other brain regions. We therefore provide an overview of the effects of serotonergic signaling in brain regions of the homeostatic and hedonic regulatory systems on food intake. Furthermore, we discuss the disturbances in serotonergic signaling in obesity and its potential therapeutic implications.

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“…Finally, a double-blind trial was carried out (12 healthy men volunteers) in order to visualize the differences in radiolabeling with an administration of paroxetine versus a placebo [ 289 ]. [ 123 I]ADAM allows exploration of the variations of SERTs, particularly in the presence of various pathologies such as depression, Parkinson’s disease, and eating disorders [ 289 , 290 , 291 , 292 , 293 , 294 ]. In 2003, [ 18 F]ADAM , a fluorinated analogue of [ 123 I]ADAM with good affinity and selectivity toward SERTs (Ki = 4.8 nM), was described [ 295 , 296 ].…”

Section: Serotonin Transportermentioning

confidence: 99%