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.
Keywords: (−)-[18F]flubatine; PET; acetylcholine; nicotinic receptors; nucleus basalis of Meynert; obesity; thalamus.