Availability of Central α4β2* Nicotinic Acetylcholine Receptors in Human Obesity

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.

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 (V_T).

No overall significant difference in V_T between the individuals with obesity and the normal-weight volunteers was found, while the V_T 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 V_T 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).

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.