Availability of Central alpha 4 beta 2* Nicotinic Acetylcholine Receptors in Human Obesity

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 alpha 4 beta 2* 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 alpha 4 beta 2* 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 alpha 4 beta 2* 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/m(2); age: 39 +/- 14 years, 9 females) and 16 normal-weight controls (non-smokers, BMI: 21.9 +/- 1.7 kg/m(2); age: 28 +/- 7 years, 13 females) by using PET and the alpha 4 beta 2* nAChR selective (-)-[F-18]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). Results: 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). Conclusion: While these first data do not show greater brain alpha 4 beta 2* nAChR availability in human obesity overall, the findings of potentially aberrant alpha 4 beta 2* nAChR availability in the key brain regions that regulate feeding behavior merit further exploration.