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Relationship of Dopamine Type 2 Receptor Binding Potential With Fasting Neuroendocrine Hormones and Insulin Sensitivity in Human Obesity
Open accessAbstract
OBJECTIVE: Midbrain dopamine (DA) neurons, which are involved with reward and motivation, are modulated by hormones that regulate food intake (insulin, leptin, and acyl ghrelin [AG]). We hypothesized that these hormones are associated with deficits in DA signaling in obesity. RESEARCH DESIGN AND METHODS: We assessed the relationships between fasting levels of insulin and leptin, and AG, BMI, and insulin sensitivity index (SI) with the availability of central DA type 2 receptor (D2R). We measured D2R availability using positron emission tomography and [18F]fallypride (radioligand that competes with endogenous DA) in lean (n = 8) and obese (n = 14) females. Fasting hormones were collected prior to scanning and SI was determined by modified oral glucose tolerance test. RESULTS: Parametric image analyses revealed associations between each metabolic measure and D2R. The most extensive findings were negative associations of AG with clusters involving the striatum and inferior temporal cortices. Regional regression analyses also found extensive negative relationships between AG and D2R in the caudate, putamen, ventral striatum (VS), amygdala, and temporal lobes. SI was negatively associated with D2R in the VS, while insulin was not. In the caudate, BMI and leptin were positively associated with D2R availability. The direction of associations of leptin and AG with D2R availability are consistent with their opposite effects on DA levels (decreasing and increasing, respectively). After adjusting for BMI, AG maintained a significant relationship in the VS. We hypothesize that the increased D2R availability in obese subjects reflects relatively reduced DA levels competing with the radioligand. CONCLUSIONS: Our findings provide evidence for an association between the neuroendocrine hormones and DA brain signaling in obese females.
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“This is consistent with preclinical (40) and clinical (41) studies showing dynamic associations between the changes in neuroendocrine hormones (e.g. insulin, leptin, ghrelin) triggered by food restriction and brain DA signalling and those of recent reports of a relationship between addictive personality and maladaptive eating behaviours following bariatric surgery (42,43).”
From Obesity and addiction: Neurobiological overlaps (2013) · cites this paper as [41]
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BackgroundThe adaptive bases algorithm for intensity-based nonrigid image registration
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MethodAlterations in the dynamics of circulating ghrelin, adiponectin, and leptin in human obesity
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BackgroundGhrelin Increases the Rewarding Value of High-Fat Diet in an Orexin-Dependent Manner
Perelló, M., Sakata, I., Birnbaum, S. G., Chuang, J.-C., Osborne-Lawrence, S. L., Rovinsky, S. A., Wołoszyn, J., Yanagisawa, M., Lutter, M. L., & Zigman, J. M. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.10.030 · Cited by 385
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“They also diminish the sensitivity of DA pathways to food reward (2), whichmay reflect the ability of insulin (8) and leptin (9) to enhance removal of DA from the synaptic cleft by the DA transporter.”
BackgroundInsulin, leptin, and food reward: update 2008
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ResultSelf-citationSeparable Substrates for Anticipatory and Consummatory Food Chemosensation
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“Low DA levels are reported in animal models of obesity (28,31) and in human drug addiction (32), another state of impaired hedonic processes.”
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“CONCLUSIONSdOur findings reveal strong associations between DA D2R availability and metabolic measures, including neuroendocrine hormones, insulin sensitivity, and BMI, that were corroborated by both parametric imaging analyses and ROI analysis (17).”
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BackgroundSelf-citationAmphetamine-induced displacement of [18F] fallypride in striatum and extrastriatal regions in humans
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“They also diminish the sensitivity of DA pathways to food reward (2), whichmay reflect the ability of insulin (8) and leptin (9) to enhance removal of DA from the synaptic cleft by the DA transporter.”
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“The negative effect of insulin on reward has been known for some time (2), while more recent studies demonstrate that insulin’s second messenger signaling modulates the cell surface expression of the DA transporter (23).”
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The dopamine motive system: implications for drug and food addiction
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“This is consistent with preclinical (40) and clinical (41) studies showing dynamic associations between the changes in neuroendocrine hormones (e.”
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“As a consequence, the choice of a neuromodulation strategy cannot rest on a single criterion (e.g. balance between the severity of disease — e.g. high BMI with comorbidities — and the invasiveness of therapy), but on multiple assessment criteria, of which some of these are directlyrelatedtothepatient 3 sphenotypeandso…”
InfluentialUpadhyay, J., Farr, O. M., Perakakis, N., Ghaly, W., & Mantzoros, C. S. (2017) · Medical Clinics of North America · doi:10.1016/j.mcna.2017.08.004 · Cited by 425
Metadata
- Authors
- Dunn, J. P., Kessler, R. M., Feurer, I. D., Volkow, N. D., Patterson, B. W., Ansari, M. S., Li, R., Marks-Shulman, P., & Abumrad, N. N.
- Affiliations
- Vanderbilt University (US)
- National Institute on Drug Abuse (US)
- Washington University in St. Louis (US)
- Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee
- Corresponding author
- Dunn, Julia P.
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2012-04-11
- Volume
- 35
- Issue
- 5
- Pages
- 1105-1111
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC3329842
- OpenAlex
- W2003413351
- Cited by
- 148
- References
- 40
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 10 · 2022: 7 · 2021: 8 · 2020: 9 · 2019: 16 · 2018: 14 · 2017: 13 · 2016: 16 · 2015: 15 · 2014: 17 · 2013: 9 · 2012: 4
- FWCI
- 6.32
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Diabetes Care (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs (IK2 CX000943)
- Vanderbilt University
- National Institutes of Health (-015855, 5p60dk020593-31, DK 20593)
- Vanderbilt Digestive Diseases Research Center, Vanderbilt University Medical Center
- National Institute of Diabetes and Digestive and Kidney Diseases (DK058404, P60-DK020593, R01DK091748, DK 20593, DK 70860, R01DK070860, 56341, P30DK058404, P30DK056341, P30DK020593)
- National Institute of Environmental Health Sciences (K12ES015855)
- National Center for Research Resources (KL2RR024977, TL1RR024978, UL1RR024975)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- dopamine D2 receptor, obesity, insulin sensitivity, leptin, acylated ghrelin, insulin, neuroendocrine hormones, ventral striatum, caudate nucleus, putamen, amygdala, striatum, inferior temporal cortex, female, food intake regulation
- MeSH terms
- Adult, Basal Ganglia, Fasting, Female, Humans, Insulin Resistance, Middle Aged, Obesity, Body Mass Index, Receptors, Dopamine D2, Leptin, Positron-Emission Tomography, Ghrelin
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