Brain, Obesity, Dopamine and You Study
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Obesity Weight Loss |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 18 - 40 |
| Updated: | 4/21/2016 |
| Start Date: | July 2010 |
| End Date: | June 2016 |
Central Dopamine Receptors In Obesity
Central dopamine is thought to play a significant role in obesity. In support of this idea,
animal studies and one human positron emission tomography (PET) study have found reduced
postsynaptic D2-like receptor availability in the striatum in obesity, with lower D2
receptor availability associated with higher weight. In addition, reward sensitivity and
hedonic responses, known to be related to dopamine function, have also been implicated in
obesity and obesity-related eating behavior. These reports have led to the concept that
dopaminergic abnormalities (e.g. reduced D2-like receptors) influence reward sensitivity,
leading to altered eating behaviors and eventually obesity. However, there are several
critical limitations of the human D2 receptor studies that limit the strength of their
conclusions and thus the interpretations and speculations embedded in literature that relies
on this work. First, estimates of D2-like receptors in humans have been confounded by
potential differences in endogenous dopamine release since the PET ligand (raclopride) used
is known to be displaceable from receptors by endogenous dopamine. Second, failure to
rigorously screen obese individuals for diabetes confounds conclusions, since diabetes has
been independently associated with dopaminergic abnormalities such as reduced D2-like
receptors and muted dopamine release in diabetic rats. Finally, no human studies have
addressed whether reduced D2-like receptor levels are a risk factor for obesity, a
consequence of engaging in obesity-related behaviors or being obese or all of the above.
animal studies and one human positron emission tomography (PET) study have found reduced
postsynaptic D2-like receptor availability in the striatum in obesity, with lower D2
receptor availability associated with higher weight. In addition, reward sensitivity and
hedonic responses, known to be related to dopamine function, have also been implicated in
obesity and obesity-related eating behavior. These reports have led to the concept that
dopaminergic abnormalities (e.g. reduced D2-like receptors) influence reward sensitivity,
leading to altered eating behaviors and eventually obesity. However, there are several
critical limitations of the human D2 receptor studies that limit the strength of their
conclusions and thus the interpretations and speculations embedded in literature that relies
on this work. First, estimates of D2-like receptors in humans have been confounded by
potential differences in endogenous dopamine release since the PET ligand (raclopride) used
is known to be displaceable from receptors by endogenous dopamine. Second, failure to
rigorously screen obese individuals for diabetes confounds conclusions, since diabetes has
been independently associated with dopaminergic abnormalities such as reduced D2-like
receptors and muted dopamine release in diabetic rats. Finally, no human studies have
addressed whether reduced D2-like receptor levels are a risk factor for obesity, a
consequence of engaging in obesity-related behaviors or being obese or all of the above.
Inclusion Criteria:
- 41 obese adults (BMI 33 kg - 45 kg.)
- 24 lean adults (BMI 18.5 kg - 24.9 kg.)
Exclusion Criteria:
- Subjects who are:
1. smokers,
2. pregnant or lactating, postmenopausal,
3. have diabetes or impaired oral glucose tolerance (fasting blood glucose level of
< 100 mg/dl and a 2 hour post-glucose challenge plasma glucose level of <
140mg/dl, per ADA criteria; ADA 2004),
4. significant organ system dysfunction, anemia (Hb <10 g/dl),
5. take medications that could influence the study results, any history of dopamine
agonist or antagonist treatment (e.g. neuroleptics or metoclopramide),
6. parkinsonism on exam,
7. borderline or lower IQ (<80 full scaled score), or
8. any psychiatric or neurologic illness (e.g. drug abuse, Parkinson disease,
Tourette syndrome, stroke) that could affect the interpretation of the data,
compliance or completion of the study will be excluded. Specific psychiatric
exclusions are lifetime psychosis, current mania, substance dependence, major
depression, social phobia, tic disorders, eating disorders and panic disorder.
Dysthymia will not be excluded, but levels of depression will be measured with
the BDI for future exploratory analysis.
- Lean subjects will be excluded for being obese in the past (based on maximum BMI not
related to pregnancy).
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