Background: Alterations of hypothalamic–pituitary–adrenal (HPA) axis activity and serotonergic
signaling are implicated in the pathogenesis of human obesity and may contribute to
its metabolic and mental complications. The association of these systems has not been investigated
in human obesity. Objective: To investigate the relation of HPA responsiveness and serotonin
transporter (5-HTT) availability in otherwise healthy individuals with obesity class II or III
(OB) compared to non-obesity controls (NO). Study participants: Twenty-eight OB (21 females;
age 36.6 10.6 years; body mass index (BMI) 41.2 5.1 kg/m2) were compared to 12 healthy NO
(8 females; age 35.8 7.4 years; BMI 22.4 2.3 kg/m2), matched for age and sex. Methods: HPA
axis responsiveness was investigated using the combined dexamethasone/corticotropin-releasing
hormone (dex/CRH) test, and curve indicators were derived for cortisol and adrenocorticotropic
hormone (ACTH). The 5-HTT selective tracer [11C]DASB was applied, and parametric images of the
binding potentials (BPND) were calculated using the multilinear reference tissue model and evaluated
by atlas-based volume of interest (VOI) analysis. The self-questionnaires of behavioral inhibition
system/behavioral activation system (BIS/BAS) with subscales drive, fun-seeking and reward were
assessed. Results: OB showed significant positive correlations of ACTH curve parameters with overall
5-HTT BPND (ACTHAUC: r = 0.39, p = 0.04) and 5-HTT BPND of the caudate nucleus (ACTHAUC:
r = 0.54, p = 0.003). In NO, cortisol indicators correlated significantly with BPND in the hippocampus
(cortisolAUC: r = 0.59, p = 0.04). In OB, BAS reward was inversely associated with the ACTHAUC
(r = 0.49, p = 0.009). Conclusion: The present study supports a serotonergic-neuroendocrine association,
which regionally differs between OB and NO. In OB, areas processing emotion and reward
seem to be in-volved. The finding of a serotonergic HPA correlation may have implications for other
diseases with dysregulated stress axis responsiveness, and for potential pharmacologic interven-tions.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:92848 |
| Date | 31 July 2024 |
| Creators | Schinke, Christian, Rullmann, Michael, Luthardt, Julia, Drabe, Mandy, Preller, Elisa, Becker, Georg A., Patt, Marianne, Regenthal, Ralf, Zientek, Franziska, Sabri, Osama, Bergh, Florian Then, Hesse, Swen |
| Publisher | MDPI AG |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2076-3425, 10.3390/brainsci12111430 |
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