Correlation between body mass index and striatal dopamine transporter availability in healthy volunteers—A SPECT study
Introduction
The Body Mass Index (BMI), which is a reliable indicator of body fitness for most people, is used to screen for weight categories that may lead to health problems. The BMI became popular during the early 1980s as rates of obesity climbed sharply over the preceding decades. The regulation of the BMI is complex (Bornstein et al., 2006a, Bornstein et al., 2006b). Several feedback pathways acting in the brain sense the caloric stores and orchestrate adjustments in energy balance and food intake to regulate the BMI. Among the peripheral metabolic signals, insulin and leptin have been proposed to act as adiposity signals and also as a part of a negative feedback loop in the hypothalamic sites. In addition, plasma glucose levels are also involved in the homeostasis regulation feedback pathway in the CNS (Pontieri et al., 2006).
Human studies have revealed that the dopaminergic system in the brain may influence factors that regulate the BMI (Martel and Fantino, 1996). Drugs that increase brain dopamine concentration are anorexigenic. In contrast, drugs that block dopamine D2 receptors can increase appetite and result in significant weight gain (Chen et al., 2004, Owens et al., 2005). Interestingly, evidences suggest that the peripheral regulators may interact with the brain’s dopaminergic system to regulate the BMI (Pelchat et al., 2004). Recent animal research has demonstrated that, in addition to the hypothalamic sites, dopamine neurons may be another target for insulin and leptin actions (Fulton et al., 2006, Hommel et al., 2006). Insulin and leptin receptors are known to express in the ventral tegmental area and substantia nigra (Figlewicz et al., 2003).
Although the striatal dopamine system traditionally forms circuits that participate in motor coordination (Yang et al., 2003), this system may also be involved in the integration of cognitive activities and reward responses through the cortico-thalamic-basal ganglian-cortical loop (Chen et al., 2005). Wang et al. (2001) demonstrated that the striatal dopamine system may be involved in the regulation of the BMI. They found that the striatal dopaminergic receptor (DRD2) availability was reduced in very obese individuals in proportion to their BMI. The goal of this study was to assess the relationship between the striatum DAT availability and the BMI in healthy individuals using SPECT with [99mTc]-TRODAT as the ligand. In addition, we also examined the relationship between some peripheral metabolic signals, including serum glucose, leptin and insulin levels, and the striatal DAT availability.
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Ethics
The Ethical Committee for Human Research at the National Cheng Kung University Medical Center approved the study protocol. Before any procedure was performed, informed consent had been obtained from the volunteers.
Participants
Healthy volunteers were recruited through advertisements. Fifty participants (23 men and 27 women; 2 left-handed) completed all of the examinations. Their age ranged from 20 to 57 years, with a mean age of 30.3 years. Their height ranged from 141 cm to 184 cm, with a mean height of
Results
The laboratory measurements of the participants were as follows: leptin: 25.44 ± 23.65 ng/ml, insulin: 7.97 ± 3.79 μIU/ml; C-peptide: 1.57 ± 0.95 ng/ml; blood sugar: 87.9 ± 7.54 ng/dl; HbA1c: 5.37 ± 0.38%. The striatal dopamine transporter availabilities for each hemisphere were estimated as follows: 2.23 ± 0.23 for both hemispheres, 2.23 ± 0.23 for the right hemisphere, and 2.24 ± 0.23 for the left hemisphere.
The correlation analyses revealed a significant negative correlation between the striatal DAT
Discussion
Functional neuroimaging techniques have recently emerged as new tools for identifying which regions of the brain are involved in the regulation of eating behaviors and those are involved in the pathophysiology of obesity (Pannacciulli et al., 2006, Porubska et al., 2006, Tataranni and DelParigi, 2003). In the current study, SPECT was used to demonstrate that lower DAT availability in the striatum was correlated with the higher BMI in healthy individuals.
The decline in DAT binding in the
Acknowledgments
The authors gratefully acknowledge the financial support from the Atomic Energy Council of Taiwan (92-NU-7-006-004) and the National Science Council of Taiwan (NSC93-2314-B-006-107), as well as the administrative support of Mlles. Ching Lin Chu and Linda J. Chang, and Mr. Wen Jui Wu.
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