Brain dopamine and obesity.
Lancet. 2001 Feb 3;357(9253):354-7.
Wang GJ, Volkow ND, Logan J, Pappas NR, Wong CT, Zhu W, Netusil N, Fowler JS.
Department of Medicine, Brookhaven National Laboratory, Upton, New York 11973, USA. giwang@bnl.gov
BACKGROUND: The cerebral mechanisms underlying the behaviours that lead to pathological overeating and obesity are poorly understood. Dopamine, a neurotransmitter that modulates rewarding properties of food, is likely to be involved. To test the hypothesis that obese individuals have abnormalities in brain dopamine activity we measured the availability of dopamine D2 receptors in brain. METHODS: Brain dopamine D2 receptor availability was measured with positron emission tomography (PET) and [C-11]raclopride (a radioligand for the dopamine D2 receptor). Bmax/Kd (ratio of the distribution volumes in striatum to that in cerebellum minus 1) was used as a measure of dopamine D2 receptor availability. Brain glucose metabolism was also assessed with 2-deoxy-2[18F]fluoro-D-glucose (FDG). FINDINGS: Striatal dopamine D2 receptor availability was significantly lower in the ten obese individuals (2.47 [SD 0.36]) than in controls (2.99 [0.41]; p < or = 0.0075). In the obese individuals body mass index (BMI) correlated negatively with the measures of D2 receptors (r=0.84; p < or = 0.002); the individuals with the lowest D2 values had the largest BMI. By contrast, neither whole brain nor striatal metabolism differed between obese individuals and controls, indicating that striatal reductions in D2 receptors were not due to a systematic reduction in radiotracer delivery. INTERPRETATION: The availability of dopamine D2 receptor was decreased in obese individuals in proportion to their BMI. Dopamine modulates motivation and reward circuits and hence dopamine deficiency in obese individuals may perpetuate pathological eating as a means to compensate for decreased activation of these circuits. Strategies aimed at improving dopamine function may be beneficial in the treatment of obese individuals.
Exposure to appetitive food stimuli markedly activates the human brain.
Neuroimage. 2004 Apr;21(4):1790-7.
Wang GJ, Volkow ND, Telang F, Jayne M, Ma J, Rao M, Zhu W, Wong CT, Pappas NR, Geliebter A, Fowler JS. Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA. gjwang@bnl.gov
OBJECTIVE: The increased incidence of obesity most likely reflects changes in the environment that had made food more available and palatable. Here we assess the response of the human brain to the presentation of appetitive food stimuli during food presentation using PET and FDG. METHOD: Metabolic changes in response to food presentation were done in 12 healthy normal body weight subjects who were food deprived before the study. RESULTS: Food presentation significantly increased metabolism in the whole brain (24%, P < 0.01) and these changes were largest in superior temporal, anterior insula, and orbitofrontal cortices. The increases in the right orbitofrontal cortex were the ones that correlated significantly with the increases in self-reports of hunger and desire for food. DISCUSSION: The marked increase in brain metabolism by the presentation of food provides evidence of the high sensitivity of the human brain to food stimuli. This high sensitivity coupled with the ubiquitousness of food stimuli in the environment is likely to contribute to the epidemic of obesity. In particular, the activation of the right orbitofrontal cortex, a brain region involved with drive, may underlie the motivation to procure food, which may be subjectively experienced as "desire for food" and "hunger" when exposed to food stimuli.
The role of dopamine in motivation for food in humans: implications for obesity.
Expert Opin Ther Targets. 2002 Oct;6(5):601-9.
Wang GJ, Volkow ND, Fowler JS.
Medical and Chemistry Departments, Brookhaven National Laboratory, Upton, NY 11973, USA. gjwang@bnl.gov
Obesity is a major public health problem. The increasing number of obese individuals in the US adds urgency to the efforts to understand the mechanisms underlying pathological overeating. Imaging studies using positron emission tomography implicate the involvement of brain dopamine (DA) in normal and pathological food intake in humans. In normal body weight, fasting subjects, food presentation that could not be consumed was associated with increases in striatal extracellular DA, which provides evidence of an involvement of DA in non-hedonic motivational properties of food intake. In pathologically obese subjects, the authors showed reductions in striatal D2 receptor availability that were inversely associated with the weight of the subject. The involvement of the DA system in reward and reinforcement has led to the hypothesis that low brain DA activity in obese subjects predisposes them to excessive use of food. A better understanding of the role of the DA system in the motivation for food intake will help the development of better therapeutic interventions.
Enhanced resting activity of the oral somatosensory cortex in obese subjects.
Neuroreport. 2002 Jul 2;13(9):1151-5. Wang GJ, Volkow ND, Felder C, Fowler JS, Levy AV, Pappas NR, Wong CT, Zhu W, Netusil N.
Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA.
The cerebral mechanisms underlying excess food intake in obese subjects are poorly understood. We used PET and 2-deoxy-2[18F]fluoro-D-glucose to assess differences in regional brain metabolism between obese and lean subjects at rest. Brain metabolic images were analyzed using statistical parameter maps. We found that obese subjects have significantly higher metabolic activity in the bilateral parietal somatosensory cortex in the regions where sensation to the mouth, lips and tongue are located. The enhanced activity in somatosensory regions involved with sensory processing of food in the obese subjects could make them more sensitive to the rewarding properties of food related to palatability and could be one of the variables contributing to their excess food consumption.
