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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Changes in neuroendocrine hormones triggered by food restriction are dynamically associated with brain DA signalling, and addictive personality is related to maladaptive eating behaviours following bariatric surgery.
“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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Eisenstein, S. A., Antenor‐Dorsey, J. A. V., Gredysa, D. M., Koller, J. M., Bihun, E. C., Ranck, S. A., Arbeláez, A. M., Klein, S., Perlmutter, J. S., Moerlein, S. M., et al. (2013) · Synapse · doi:10.1002/syn.21680 · Cited by 85 · see citing works
“The power of our study to detect differences in D2R BPND estimates between normal-weight and obese groups as well as to detect correlations between D2R BPND estimates and BMI in the obese group was calculated based on results from previous studies of D2=D3 receptor availability (de Weijer et al., 2011; Dunn et al., 20…”
BackgroundMethodResultInfluentialHajnal, A. S., Zharikov, A., Polston, J. E., Fields, M. R., Tomasko, J. M., Rogers, A. M., Volkow, N. D., & Thanos, P. K. (2012) · PLoS ONE · doi:10.1371/journal.pone.0049121 · Cited by 86 · see citing works
“Furthermore, hormones that have been shown to change after RYGB, such as leptin and ghrelin [35,36,37], are also known to modulate the dopaminergic reward system [38,39,40,41] as well as alcohol consumption [41,42,43].”
BackgroundSelf-citationFood Addiction and Binge Eating: Lessons Learned from Animal Models
Novelle, M. G., & Diéguez, C. (2018) · Nutrients · doi:10.3390/nu10010071 · Cited by 86 · see citing works
“Contrarily, other groups have shown higher striatal DA in obese individuals [77,99].”
ResultDopaminergic Control of the Feeding Circuit
Baik, J. (2021) · Endocrinology and Metabolism · doi:10.3803/enm.2021.979 · Cited by 81 · see citing works
“Individuals who carried one or more copies of TaqI A1 and were homozygous for the Lys109Arg LEPR variant had a significantly higher BMI than carriers of all other alleles, suggesting a possible critical interaction between dopamine and the leptin system through D2R, although no independent association between Lys109RA…”
BackgroundMethodInfluentialCaravaggio, F., Borlido, C., Hahn, M., Feng, Z., Fervaha, G., Gerretsen, P., Nakajima, S., Plitman, E., Chung, J. K., Iwata, Y., et al. (2015) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyv014 · Cited by 76 · see citing works
“…of subjects (n = 11), examination of correlations between participant metabolic variables revealed that age was positively correlated with waist circumference (r(9) = .76, P = .007), and waist circumference was positively correlated with fasting levels of insulin (r(9) = .80, P = .003) (Table 2).”
BackgroundDopamine D 2/3 receptor availability and amphetamine-induced dopamine release in obesity
van de Giessen, E., Celik, F., Schweitzer, D. H., van den Brink, W., & Booij, J. (2014) · Journal of Psychopharmacology · doi:10.1177/0269881114531664 · Cited by 74 · see citing works
Fuel not fun: Reinterpreting attenuated brain responses to reward in obesity
Kroemer, N. B., & Small, D. M. (2016) · Physiology & Behavior · doi:10.1016/j.physbeh.2016.04.020 · Cited by 73 · see citing works
“Below we consider the possibility that the robust inverse association between BMI and dorsal striatal responses to nutrient intake is an indication of attenuated rewardrelated learning signals.”
BackgroundInfluentialMesolimbic dopamine and its neuromodulators in obesity and binge eating
Naef, L., Pitman, K. A., & Borgland, S. L. (2015) · CNS Spectrums · doi:10.1017/s1092852915000693 · Cited by 70 · see citing works
“Most studies examining the relationship between human obesity and dopamine D2 (and D4) receptor availability have revealed a decrease in D2 receptor availability in obesity, although increased availability has also been reported in fasted obese subjects.(29) One important caveat with some of the human literature is th…”
BackgroundAssociations between dopamine D2 receptor availability and BMI depend on age
Dang, L. C., Samanez-Larkin, G. R., Castrellon, J. J., Perkins, S. F., Cowan, R. L., & Zald, D. H. (2016) · NeuroImage · doi:10.1016/j.neuroimage.2016.05.044 · Cited by 66 · see citing works
“It may be that beyond a certain age, changes in DRD2 affinity state cause the positive relation between BPnd and BMI to be more prominent and observable with high affinity DRD2/3 ligands, such as 11C]-(+)-PHNO and [18F]fallypride (Cosgrove et al., 2015; Dunn et al., 2012; Caravaggio et al., 2015).”
BackgroundInfluentialMechanisms of insulin resistance in the amygdala: Influences on food intake
Areias, M. F. C., & Prada, P. O. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.01.003 · Cited by 61 · see citing works
Gold, M. S., Baron, D. A., Bowirrat, A., & Blum, K. (2020) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2020.117137 · Cited by 57 · see citing works
Persistent effects of obesity: A neuroplasticity hypothesis
Matikainen‐Ankney, B. A., & Kravitz, A. V. (2018) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13665 · Cited by 56 · see citing works
Food and addiction among the ageing population
Murray, S. M., Kroll, C., & Avena, N. M. (2014) · Ageing Research Reviews · doi:10.1016/j.arr.2014.10.002 · Cited by 55 · see citing works
Central Insulin Modulates Dopamine Signaling in the Human Striatum
Kullmann, S., Blum, D., Jaghutriz, B. A., Gassenmaier, C., Bender, B., Häring, H., Reischl, G., Preissl, H. T., la Fougère, C. J., Fritsche, A., et al. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab410 · Cited by 54 · see citing works
Insulin, Central Dopamine D2 Receptors, and Monetary Reward Discounting in Obesity
Eisenstein, S. A., Gredysa, D. M., Antenor‐Dorsey, J. A. V., Green, L., Arbeláez, A. M., Koller, J. M., BLACK, K. J., Perlmutter, J. S., Moerlein, S. M., & Hershey, T. G. (2015) · PLoS ONE · doi:10.1371/journal.pone.0133621 · Cited by 54 · see citing works
“Lower insulin sensitivity is associated with increased brain activation induced by food images [24] and increased striatal D2-like receptor binding [3].”
BackgroundFoxO1 in dopaminergic neurons regulates energy homeostasis and targets tyrosine hydroxylase
Doan, K. V., Kinyua, A. W., Yang, D. J., Ko, C. M., Moh, S. H., Shong, K. E., Kim, H., Park, S.-K., Kim, D. H., Kim, I., et al. (2016) · Nature Communications · doi:10.1038/ncomms12733 · Cited by 54 · see citing works
de Weijer, B. A., van de Giessen, E., Janssen, I. M. C., Berends, F. J., van de Laar, A. W. J. M., Ackermans, M. T., Fliers, E., la Fleur, S. E., Booij, J., & Serlie, M. J. M. (2014) · Diabetologia · doi:10.1007/s00125-014-3178-z · Cited by 53 · see citing works
“Furthermore, a correlation between the insulin sensitivity index (SI) and D2/3R availability in the ventral striatum has been reported [10].”
BackgroundWoods, C. A., Guttman, Z. R., Huang, D., Kolaric, R., Rabinowitsch, A. I., Jones, K. T., de Vaca, S. C., Sclafani, A. J., & Carr, K. D. (2016) · Physiology & Behavior · doi:10.1016/j.physbeh.2016.03.013 · Cited by 52 · see citing works
“, 2006) and insulin sensitivity correlates with D2 DA receptor availability (Dunn et al., 2012).”
BackgroundResultvan der Zwaal, E. M., de Weijer, B. A., van de Giessen, E., Janssen, I. M. C., Berends, F. J., van de Laar, A. W. J. M., Ackermans, M. T., Fliers, E., la Fleur, S. E., Booij, J., et al. (2016) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2016.04.009 · Cited by 52 · see citing works
“The unchanged ghrelin levels after RYGB in this study are in line with previous findings (Stoeckli et al., 2004) but in contrast to the study by Dunn et al., we observed no correlations between changes in BPND and changes in plasma levels of ghrelin (Dunn et al., 2012).”
InfluentialRoux-en-Y Gastric Bypass Increases Intravenous Ethanol Self-Administration in Dietary Obese Rats
Polston, J. E., Pritchett, C. E., Tomasko, J. M., Rogers, A. M., Leggio, L., Thanos, P. K., Volkow, N. D., & Hajnal, A. S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0083741 · Cited by 50 · see citing works
“Notably, hormones that have been shown to change after RYGB, such as leptin and ghrelin [26,27,28], are also known to modulate the dopaminergic reward system [29,30,31] as well as EtOH consumption [32,33].”
BackgroundSelf-citationMathar, D., Neumann, J., Villringer, A., & Horstmann, A. (2017) · Cortex · doi:10.1016/j.cortex.2017.08.022 · Cited by 49 · see citing works
Eisenstein, S. A., Bischoff, A. N., Gredysa, D. M., Antenor‐Dorsey, J. A. V., Koller, J. M., Al-Lozi, A. M., Pepino, M. Y., Klein, S., Perlmutter, J. S., Moerlein, S. M., et al. (2015) · Scientific Reports · doi:10.1038/srep11283 · Cited by 48 · see citing works
Do Dopaminergic Impairments Underlie Physical Inactivity in People with Obesity?
Kravitz, A. V., O’Neal, T. J., & Friend, D. M. (2016) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2016.00514 · Cited by 48 · see citing works
Brain on Fire: Incentive Salience, Hedonic Hot Spots, Dopamine, Obesity, and Other Hunger Games
Cameron, J. D., Chaput, J., Sjödin, A. M., & Goldfield, G. S. (2017) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071816-064855 · Cited by 48 · see citing works
Circulating acyl and des-acyl ghrelin levels in obese adults: a systematic review and meta-analysis
Wang, Y., Wu, Q., Zhou, Q., Chen, Y., Lei, X., Chen, Y., & Chen, Q. (2022) · Scientific Reports · doi:10.1038/s41598-022-06636-3 · Cited by 46 · see citing works
Labouesse, M. A., Sartori, A. M., Weinmann, O., Simpson, E. H., Kellendonk, C., & Weber‐Stadlbauer, U. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1800171115 · Cited by 45 · see citing works
Comparing the effects of food restriction and overeating on brain reward systems
Avena, N. M., Murray, S. M., & Gold, M. S. (2013) · Experimental Gerontology · doi:10.1016/j.exger.2013.03.006 · Cited by 44 · see citing works
“Adding to the complexity of this issue, research has shown both that obese individuals have less D2 receptor binding compared to normal and overweight controls (Wang et al., 2001), as well as that higher BMI is related to increased D2 availability (Dunn et al., 2012).”
BackgroundOrellana, E. R., Covașă, M., & Hajnal, A. S. (2019) · Biochemical Pharmacology · doi:10.1016/j.bcp.2019.04.004 · Cited by 43 · see citing works
Horstmann, A. (2017) · Physiology & Behavior · doi:10.1016/j.physbeh.2017.04.001 · Cited by 38 · see citing works
A narrative review of highly processed food addiction across the lifespan
Schiestl, E. T., Rios, J. M., Parnarouskis, L., Cummings, J. R., & Gearhardt, A. N. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.110152 · Cited by 38 · see citing works
“Furthermore, recent research suggests that hyperinsulinemia in response to high-glycemic food intake may be responsible for driving neurochemical changes associated with HP food addiction (Caravaggio et al., 2015; Caravaggio et al., 2018; Dunn et al., 2012).”
BackgroundDrummen, M., Dorenbos, E., Vreugdenhil, A. C. E., Raben, A., Westerterp‐Plantenga, M. S., & Adam, T. C. (2018) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqy252 · Cited by 37 · see citing works
An Overview of Appetite-Regulatory Peptides in Addiction Processes; From Bench to Bed Side
Shevchouk, O. T., Tufvesson‐Alm, M., & Jerlhag, E. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.774050 · Cited by 37 · see citing works
Lipids and obesity: Also a matter of taste?
Besnard, P. (2016) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-016-9355-2 · Cited by 36 · see citing works
“ability in NAc and VTA being found by several groups [84–86], while no difference [87, 88] or a rise [89, 90] were”
Effort-based decision-making is affected by overweight/obesity in major depressive disorder
Mansur, R. B., Subramaniapillai, M., Zuckerman, H., Park, C., Iacobucci, M., Lee, Y. L., Tuineag, M., Hawco, C. S., Frey, B. N., Rasgon, N., et al. (2019) · Journal of Affective Disorders · doi:10.1016/j.jad.2019.06.002 · Cited by 38 · see citing works
Taste of Fat and Obesity: Different Hypotheses and Our Point of View
Brondel, L., Quilliot, D., Mouillot, T., Khan, N. A., Bastable, P., Boggio, V., Leloup, C., & Pénicaud, L. (2022) · Nutrients · doi:10.3390/nu14030555 · Cited by 36 · see citing works
Janssen, L. K., & Horstmann, A. (2022) · Brain Sciences · doi:10.3390/brainsci12040486 · Cited by 36 · see citing works
“, 2012 [43] [18F]-Fallypride D2/D3 BPND CAU, PUT, vSTR, SN 8:0 NW 23(2) <25 40(9) Fasted (8 h before scanning) None Secondary OB > NW in CAU 14:0 OB 40(5) >30 40(8)”
MethodResultLower dopamine tone in the striatum is associated with higher body mass index
Lee, Y., Kroemer, N. B., Oehme, L., Beuthien‐Baumann, B., Goschke, T., & Smolka, M. N. (2018) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2018.03.009 · Cited by 34 · see citing works
Neurobehavioral determinants of nutritional security in fetal growth–restricted individuals
Portella, A. K., & Silveira, P. P. (2014) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12390 · Cited by 34 · see citing works
Incidental rewarding cues influence economic decisions in people with obesity
Simmank, J., Murawski, C., Bode, S., & Horstmann, A. (2015) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2015.00278 · Cited by 32 · see citing works
“…in Behavioral Neuroscience | www.frontiersin.org 12 October 2015 | Volume 9 | Article 278 by non-linear changes within the central balance of phasic and tonic dopaminergic signaling (Wang et al., 2001; de Weijer et al., 2011; Dunn et al., 2012; Guo et al., 2014; Horstmann et al., 2015a).”
BackgroundMethodInfluentialVinik, A. I., Cincotta, A. H., Scranton, R. E., Bohannon, N. J. V., Ezrokhi, M., & Gaziano, J. M. (2012) · Endocrine Practice · doi:10.4158/ep12187.or · Cited by 33 · see citing works
Orellana, E. R., Jamis, C., Horvath, N., & Hajnal, A. S. (2017) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2017.08.004 · Cited by 33 · see citing works
Mansur, R. B., Fries, G. R., Subramaniapillai, M., Frangou, S., Felice, F. G. D., Rasgon, N., McEwen, B. S., Brietzke, E. M., & McIntyre, R. S. (2018) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2018.10.020 · Cited by 33 · see citing works
Hartmann, H., Pauli, L. K., Janssen, L. K., Hühn, S., Ceglarek, U., & Horstmann, A. (2020) · Journal of Neuroendocrinology · doi:10.1111/jne.12917 · Cited by 33 · see citing works
MacIntosh, B., Shirzadi, Z., Atwi, S., Detre, J., Dolui, S., Bryan, R., Launer, L., & Swardfager, W. (2019) · Human Brain Mapping · doi:10.1002/hbm.24844 · Cited by 32 · see citing works
“…changes in neural circuits, such as the prefrontal and ventral striatal regions involved in food reward processing, self-regulation and stress (Dunn et al., 2012; Ottino-González et al., 2017), which could influence regional neurovascular metabolism and hence, CBF. Evidence in support of…”
BackgroundSerotonin Transporter Binding in the Diencephalon Is Reduced in Insulin-Resistant Obese Humans
Versteeg, R. I., Koopman, K. E., Booij, J., Ackermans, M. T., Unmehopa, U. A., Fliers, E., la Fleur, S. E., & Serlie, M. J. M. (2016) · Neuroendocrinology · doi:10.1159/000450549 · Cited by 32 · see citing works
“Obese subjects have lower striatal dopamine D2/3 receptor (D2/3R) binding availability (13) and striatal D2/3R binding is associated with insulin sensitivity (14).”
The Role of Bromocriptine-Qr in the Management of Type 2 Diabetes Expert Panel Recommendations
Garber, A. J., Blonde, L., Bloomgarden, Z. T., Handelsman, Y., & Dagogo-Jack, S. E. (2013) · Endocrine Practice · doi:10.4158/ep12325.or · Cited by 31 · see citing works
Dopaminergic Pathways in Obesity-Associated Inflammation
Leite, F., & Ribeiro, L. V. P. T. (2019) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-019-09863-0 · Cited by 31 · see citing works
“…et al. 2008; Stice et al. 2013; Kenny 2011; Volkow and Wise 2005) and clinical studies (Wang et al. 2001; Haltia et al. 2007; Volkow et al. 2008; Dunn et al. 2012) suggested that overeating, particularly high-fat high-sugar diets, and obesity induces alterations on neural brain regions of the…”
BackgroundConverging vulnerability factors for compulsive food and drug use
Serafine, K. M., O’Dell, L. E., & Zorrilla, E. P. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108556 · Cited by 28 · see citing works
Kroemer, N. B., Burrasch, C., & Hellrung, L. (2016) · Progress in brain research · doi:10.1016/bs.pbr.2016.06.009 · Cited by 29 · see citing works
Savage, S. W., Zald, D. H., Cowan, R. L., Volkow, N. D., Marks-Shulman, P. A., Kessler, R. M., Abumrad, N. N., & Dunn, J. P. (2014) · Obesity · doi:10.1002/oby.20690 · Cited by 27 · see citing works
“We previously demonstrated that D2/D3R BPND in the striatum is negatively associated with fasting acyl ghrelin levels in a cohort of normal weight and obese females (10).”
Self-citationRaskin, P., & Cincotta, A. H. (2015) · Expert Review of Endocrinology & Metabolism · doi:10.1586/17446651.2016.1131119 · Cited by 28 · see citing works
O’Dell, L. E., & Nazarian, A. (2015) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2015.06.005 · Cited by 27 · see citing works
To Do or Not to Do: Dopamine, Affordability and the Economics of Opportunity
Beeler, J. A., & Mourra, D. (2018) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2018.00006 · Cited by 27 · see citing works
Dorsal Striatal Dopamine, Food Preference and Health Perception in Humans
Wallace, D. L., Aarts, E., Dang, L. C., Greer, S. M., Jagust, W. J., & D’Esposito, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0096319 · Cited by 24 · see citing works
“a positive relationship between binding and BMI, as found in [8]).”
BackgroundBabenko, V. N., Galyamina, A. G., Rogozin, I. B., Смагин, Д. А., & Kudryavtseva, N. N. (2020) · BMC Neuroscience · doi:10.1186/s12868-020-00560-w · Cited by 22 · see citing works
Obesity and Brain Positron Emission Tomography
Pak, K., Kim, S., & Kim, I. J. (2017) · Nuclear Medicine and Molecular Imaging · doi:10.1007/s13139-017-0483-8 · Cited by 21 · see citing works
“This inconsistency between studies may be related not only with the radiopharmaceuticals, but also with the experimental settings such as the time of the day, and food restriction [63].”
BackgroundKahleová, H., Tintěra, J., Thieme, L., Veleba, J., Klementová, M., Kudláčková, M., Malínská, H., Oliyarnyk, O., Marková, I., Haluzı́k, M., et al. (2019) · Clinical Nutrition · doi:10.1016/j.clnu.2020.10.005 · Cited by 20 · see citing works
Farr, O. M., & Mantzoros, C. S. (2016) · International Journal of Obesity · doi:10.1038/ijo.2016.231 · Cited by 20 · see citing works
Janssen, L. K., Herzog, N., Waltmann, M., Breuer, N., Wiencke, K., Rausch, F., Hartmann, H., Poessel, M., & Horstmann, A. (2019) · Current Addiction Reports · doi:10.1007/s40429-019-00268-w · Cited by 20 · see citing works
Obesity surgery: happy with less or eternally hungry?
Shin, A. C., & Berthoud, H. (2013) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2012.11.009 · Cited by 19 · see citing works
Striatal Dopamine Homeostasis is Altered in Mice Following Roux-en-Y Gastric Bypass Surgery
Reddy, I. A., Wasserman, D. H., Ayala, J. E., Hasty, A. H., Abumrad, N. N., & Galli, A. (2014) · ACS Chemical Neuroscience · doi:10.1021/cn500137d · Cited by 19 · see citing works
Self-citationStriatal Dopamine D2 Receptors Regulate Cost Sensitivity and Behavioral Thrift
Mourra, D., Gnazzo, F. G., Cobos, S., & Beeler, J. A. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2019.11.002 · Cited by 18 · see citing works
“Subsequent studies have yielded contradictory results (Volkow et al., 2008; de Weijer et al., 2011; Kessler et al., 2014; negative: Dunn et al., 2012; Eisenstein et al., 2013; de Weijer et al., 2014; Cosgrove et al., 2015; Karlsson et al., 2015; Tuominen et al., 2015).”
ResultEarly adversity and insulin: neuroendocrine programming beyond glucocorticoids
Batra, A., Latsko, M. S., Portella, A. K., & Silveira, P. P. (2021) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2021.09.003 · Cited by 17 · see citing works
Burke, M. V., & Small, D. M. (2016) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2016.02.036 · Cited by 17 · see citing works
la Fleur, S. E., & Serlie, M. J. M. (2014) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2014.06.001 · Cited by 16 · see citing works
Dunn, J. P., Abumrad, N. N., KESSLER, R. M., Patterson, B. W., Li, R., Marks–Shulman, P. A., & Tamboli, R. A. (2017) · Obesity · doi:10.1002/oby.22023 · Cited by 16 · see citing works
Self-citationBrain dopamine receptor system is not altered in obesity: Bayesian and frequentist meta‐analyses
Pak, K., & Nummenmaa, L. (2023) · Human Brain Mapping · doi:10.1002/hbm.26534 · Cited by 15 · see citing works
“One study with F18-Fallypride (Dunn et al., 2012) and two studies with C11-PHNO showed the higher DR availability in overweight/obese subjects while two studies with C11-Raclopride (Caravaggio et al., 2015; Haltia et al., 2008) and one study with I123-IBZM (van de Giessen et al., 2014) did not show the difference of D…”
BackgroundMethodResultInfluentialCaravaggio, F., Hahn, M., Nakajima, S., Gerretsen, P., Remington, G., & Graff-Guerrero, A. (2015) · Medical Hypotheses · doi:10.1016/j.mehy.2015.06.011 · Cited by 17 · see citing works
“These findings are consistent with previous PET studies which have employed other D2/3R radiotracers to examine the relationship between baseline D2/3R availability and insulin sensitivity [68,69].”
ResultRospond, B., Sadakierska−Chudy, A., Kazek, G., Krośniak, M., Bystrowska, B., & Filip, M. (2018) · Pharmacological Reports · doi:10.1016/j.pharep.2018.09.005 · Cited by 15 · see citing works
Striatal dopamine transporter changes after glucose loading in humans
Pak, K., Seo, S., Keun-young Kim, A., Lee, M. J., Shin, M., Suh, S., Im, H., Park, J., Kim, S., & Kim, I. J. (2019) · Diabetes Obesity and Metabolism · doi:10.1111/dom.13872 · Cited by 14 · see citing works
“As obesity can be defined as a BMI of 30 or more, individuals with both moderate and severe obesity can be included in the obese group in each study.(6,26,29) Moreover, as a fundamental limitation of DR availability acquired as assessed by PET scans is that endogenous dopamine competes with the radiopharmaceuticals fo…”
BackgroundThe dark side of compulsive eating and food addiction
Zorrilla, E. P., & Koob, G. F. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816207-1.00006-8 · Cited by 14 · see citing works
Ziomber, A., Rokita, E., Kaszuba-Zwoińska, J., Romańska, I., Michaluk, J., & Antkiewicz‐Michaluk, L. (2018) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2017.00262 · Cited by 12 · see citing works
“, 2014) other experiments showed an opposite relationship (Dunn et al., 2012) or found no association between striatal DA D2 binding and BMI (Eisenstein et al.”
ResultHartmann, H., Janssen, L. K., Herzog, N., Morys, F., Fängström, D., Fallon, S. J., & Horstmann, A. (2023) · Appetite · doi:10.1016/j.appet.2023.106477 · Cited by 11 · see citing works
Cincotta, A. H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241713255 · Cited by 11 · see citing works
Chamarthi, B., Vinik, A. I., Ezrokhi, M., & Cincotta, A. H. (2019) · Endocrinology Diabetes & Metabolism · doi:10.1002/edm2.101 · Cited by 10 · see citing works
Tabassum, A., Badulescu, S., Singh, E., Asoro, R., McIntyre, R. S., Teopiz, K. M., Llach, C.-D., Shah, H., & Mansur, R. B. (2024) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2024.105907 · Cited by 10 · see citing works
“…co-occurrence of reward and metabolic dysfunction (e.g., IR) in highly prevalent and debilitating conditions like obesity (Ziauddeen et al., 2015; Dunn et al., 2012), depression (Satterthwaite et al., 2015; Treadway and Zald, 2011; Díaz-Carías et al., 2023), anxiety (Díaz-Carías et al., 2023;…”
BackgroundAl‐Alsheikh, A. S., Alabdulkader, S., Miras, A. D., & Goldstone, A. P. (2023) · Obesity Reviews · doi:10.1111/obr.13620 · Cited by 10 · see citing works
“64 By contrast, higher BMI has been associated with higher 18 F-fallypride BP in the dorsal and lateral striatum 59 ; in caudate 65 ; in midbrain, putamen, and ventral striatum, 66 and higher N-methyl benperidol BP in caudate.”
BackgroundTowards a translational approach to food addiction: Implications for bulimia nervosa
Leslie, M., Lambert, E., & Treasure, J. (2019) · Current Addiction Reports · doi:10.1007/s40429-019-00264-0 · Cited by 9 · see citing works
“[71] conducted a positron emission tomography (PET) study using the dopamine”
MethodDarcey, V. L., Guo, J., Chi, M., Chung, S. T., Courville, A. B., Gallagher, I., Herscovitch, P., Howard, R., LaNoire, M., Milley, L., et al. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-02960-y · Cited by 18 · see citing works
- 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 › Epidemiology › 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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