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Availability of central α4β2* nicotinic acetylcholine receptors in human obesity.
Brain Sci. 12:1648 (2022)
Purpose: Obesity is thought to arise, in part, from deficits in the inhibitory control over appetitive behavior. Such motivational processes are regulated by neuromodulators, specifically acetylcholine (ACh), via α4β2* nicotinic ACh receptors (nAChR). These nAChR are highly enriched in the thalamus and contribute to the thalamic gating of cortico-striatal signaling, but also act on the mesoaccumbal reward system. The changes in α4β2* nAChR availability, however, have not been demonstrated in human obesity thus far. The aim of our study was, thus, to investigate whether there is altered brain α4β2* nAChR availability in individuals with obesity compared to normal-weight healthy controls. Methods: We studied 15 non-smoking individuals with obesity (body mass index, BMI: 37.8 ± 3.1 kg/m2; age: 39 ± 14 years, 9 females) and 16 normal-weight controls (non-smokers, BMI: 21.9 ± 1.7 kg/m2; age: 28 ± 7 years, 13 females) by using PET and the α4β2* nAChR selective (−)-[18F]flubatine, which was applied within a bolus-infusion protocol (294 ± 16 MBq). Volume-of-interest (VOI) analysis was performed in order to calculate the regional total distribution volume (VT). Results: No overall significant difference in VT between the individuals with obesity and the normal-weight volunteers was found, while the VT in the nucleus basalis of Meynert tended to be lower in the individuals with obesity (10.1 ± 2.1 versus 11.9 ± 2.2; p = 0.10), and the VT in the thalamus showed a tendency towards higher values in the individuals with obesity (26.5 ± 2.5 versus 25.9 ± 4.2; p = 0.09). Conclusion: While these first data do not show greater brain α4β2* nAChR availability in human obesity overall, the findings of potentially aberrant α4β2* nAChR availability in the key brain regions that regulate feeding behavior merit further exploration.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
(−)-[ F]flubatine 18 ; Acetylcholine ; Nicotinic Receptors ; Nucleus Basalis Of Meynert ; Obesity ; Pet ; Thalamus; Cholinergic Modulation; Desensitization; Activation; Mechanisms; Circuitry; Dopamine; Appetite
ISSN (print) / ISBN
2076-3425
e-ISSN
2076-3425
Journal
Brain Sciences
Quellenangaben
Volume: 12,
Issue: 12,
Article Number: 1648
Publisher
MDPI
Publishing Place
St Alban-anlage 66, Ch-4052 Basel, Switzerland
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)