The precise mechanism for the discovered white matter changes remains unclear, but the present study demonstrates that obesity and dieting are associated with opposite changes in brain structure. It is not excluded that white matter expansion in obesity has a role in the neuropathogenesis of degenerative brain diseases.

Dopamine is known to regulate food intake by modulating food reward via the mesolimbic circuitry of the brain. The objective of this study was to compare the effects of high energy input (i.v. glucose) on striatal and thalamic dopamine release in overweight and lean individuals. We hypothesized that glucose would induce dopamine release and positive ratings (e.g., satiety) in Behavioral Analog Scales, particularly in food-deprived lean subjects. [(11)C]raclopride PET was performed for 12 lean (mean BMI = 22 kg/m(2)) and 12 overweight (mean BMI = 33 kg/m(2)) healthy subjects. Each subject was imaged twice in a blinded counter-balanced setting, after 300 mg/kg i.v. glucose and after i.v. placebo. Dopamine D2 receptor binding potentials (BPs) were estimated. The voxel-based analysis of the baseline scans indicated lower striatal BPs in the overweight group and a negative correlation between BMIs and BPs. Intravenous glucose did not have a significant effect on BPs in overweight or lean subjects (male and female groups combined). However, BP changes were opposite in the two gender groups. In male subjects, significant BP reductions after glucose were seen in the right and left caudate nucleus, left putamen, and right thalamus. In female subjects, increases in BP secondary to glucose were seen in the right caudate nucleus and right and left putamen. The sexually dimorphic effect of glucose was seen in both overweight and lean subjects. Although gender differences were not among the a priori hypotheses of the present study and, therefore, they must be considered to be preliminary findings, we postulate that this observation is a reflection of an interaction between glucose, sex steroids (estrogen), leptin, and dopamine.

Previous positron emission tomography (PET) studies have provided evidence that the psychological expectation of certain drugs combined to the placebo administration may lead to subjectively experienced placebo effects, which, in turn, are associated with dopamine (DA) release in the brain. Our recent study indicated that blind intravenous (i.v.) glucose induces DA release in male subjects. In the present study, we examined if the mere expectation of glucose (i.v. placebo) could similarly release DA in the basal ganglia. [(11)C]raclopride PET was performed for 12 lean [mean body mass index (BMI) = 22 kg/m(2)] and 12 overweight (mean BMI = 33 kg/m(2)) healthy subjects (12 men and 12 women). Each subject was imaged twice in a counter-balanced setting, after blind i.v. placebo and after open i.v. placebo. DA D2 receptor binding potentials (BP) were estimated. The results of the present study show that i.v. placebo administration with glucose expectation induces bilateral BP reduction in the ventral striatum in the male group, suggesting DA release. The stimulus did not induce dopaminergic placebo effect in the overweight or the lean group (males and females combined). Voxel-based analysis also suggested regionally selective BP increases in the dorsal striatum in the male subjects, whereas women showed no significant changes in BPs. The results support previously reported gender differences in the DA function after a pharmacological challenge (e.g., amphetamine and glucose). Also, they suggest that the DA release in the ventral striatum mediates placebo responses in the context of glucose expectation.