Relationship of estrogen synthesis capacity in the brain with obesity and self-control in men and women

Biegon, Anat; Alia-Klein, Nelly; Alexoff, David L.; Fowler, Joanna S.; Kim, Sung Won; Logan, Jean; Pareto, Deborah; Preston-Campbell, Rebecca; Wang, Gene-Jack; Hildebrandt, Tom

doi:10.1073/pnas.2006117117

Relationship of estrogen synthesis capacity in the brain with obesity and self-control in men and women

Journal Article · Mon Aug 31 00:00:00 EDT 2020 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.2006117117· OSTI ID:1657255

^[1]; Alia-Klein, Nelly ^[2]; Alexoff, David L. ^[3]; Fowler, Joanna S. ^[4]; Kim, Sung Won ^[5]; Logan, Jean ^[6]; Pareto, Deborah ^[7]; Preston-Campbell, Rebecca ^[8]; ^[5]; Hildebrandt, Tom ^[2]

Department of Radiology &, Neurology, Stony Brook University School of Medicine, Stony Brook, NY 11794,
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029,
Fiveeleven Pharma, Philadelphia, PA 19104,
Department of Chemistry, Brookhaven National Laboratory, Upton, NY 11973,
Laboratory of Neuroimaging, National Institute on Alcoholism and Alcohol Abuse, Bethesda, MD 20892,
Department of Radiology, New York University Langone Medical Center, New York, NY 10016,
Magnetic Resonance Unit, Vall d'Hebron University Hospital, 08035 Barcelona, Spain,
Missouri Institute of Mental Health, St. Louis, MO 63134

Significance

Obesity is a major public health problem in a growing proportion of children and adults in the developed world. Estrogen influences body weight and behavioral responses to appetitive stimuli. Estrogen biosynthesis is catalyzed by the enzyme aromatase in all organs measured, including the brain. Using the aromatase radiotracer [ ¹¹ C]vorozole, we measured aromatase availability in the amygdala in healthy-weight to obese adults. Obesity was associated with lower aromatase availability and less constraint independent of sex and age. Variability in brain estrogen synthesis may contribute to obesity by directly regulating feeding and broadly by affecting self-control. These findings suggest that brain aromatase imaging offers a method for characterizing the role of brain estrogen in obesity and other impairments in self-regulation.

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Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-98CH10886

OSTI ID:: 1657255

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 37 Vol. 117; ISSN 0027-8424

Publisher:: Proceedings of the National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: English

References (67)

Differences in Obesity Prevalence by Demographic Characteristics and Urbanization Level Among Adults in the United States, 2013-2016 Hales, Craig M.; Fryar, Cheryl D.; Carroll, Margaret D. JAMA, Vol. 319, Issue 23 https://doi.org/10.1001/jama.2018.7270	journal	June 2018
Sex differences in the distribution of androgen receptors in the human hypothalamus Fern�ndez-Guasti, Alonso; Kruijver, Frank P. M.; Fodor, Mariann The Journal of Comparative Neurology, Vol. 425, Issue 3 https://doi.org/10.1002/1096-9861(20000925)425:3<422::AID-CNE7>3.0.CO;2-H	journal	January 2000
Estrogen receptor-? distribution in the human hypothalamus in relation to sex and endocrine status Kruijver, Frank P. M.; Balesar, Rawien; Espila, Ana M. The Journal of Comparative Neurology, Vol. 454, Issue 2 https://doi.org/10.1002/cne.10416	journal	October 2002
Anatomic relationships between aromatase and androgen receptor mRNA expression in the hypothalamus and amygdala of adult male cynomolgus monkeys Roselli, Charles E.; Klosterman, Scott; Resko, John A. The Journal of Comparative Neurology, Vol. 439, Issue 2 https://doi.org/10.1002/cne.1343	journal	October 2001
Unique distribution of aromatase in the human brain: In vivo studies with PET and [N-methyl-11C]vorozole Biegon, Anat; Kim, Sung Won; Alexoff, David L. Synapse, Vol. 64, Issue 11 https://doi.org/10.1002/syn.20791	journal	April 2010
Physiologic and psychological gender differences in bariatric surgery Kochkodan, Jeanne; Telem, Dana A.; Ghaferi, Amir A. Surgical Endoscopy, Vol. 32, Issue 3 https://doi.org/10.1007/s00464-017-5819-z	journal	August 2017
Relevance of Stress and Female Sex Hormones for Emotion and Cognition ter Horst, J. P.; de Kloet, E. R.; Schächinger, H. Cellular and Molecular Neurobiology, Vol. 32, Issue 5 https://doi.org/10.1007/s10571-011-9774-2	journal	November 2011
Factors Associated with Weight Loss After Metabolic Surgery in a Multiethnic Sample of 1012 Patients Masrur, Mario; Bustos, Roberto; Sanchez-Johnsen, Lisa Obesity Surgery, Vol. 30, Issue 3 https://doi.org/10.1007/s11695-019-04338-w	journal	December 2019
Effects of testosterone upon feeding in male mice Petersen, Stewart Animal Behaviour, Vol. 26 https://doi.org/10.1016/0003-3472(78)90158-6	journal	August 1978
Central implants of diluted estradiol: independent effects on ingestive and reproductive behaviors of ovariectomized rats Butera, Peter C.; Beikirch, Richard J. Brain Research, Vol. 491, Issue 2 https://doi.org/10.1016/0006-8993(89)90062-0	journal	July 1989
Current views on obesity Stunkard, Albert J. The American Journal of Medicine, Vol. 100, Issue 2 https://doi.org/10.1016/S0002-9343(97)89464-8	journal	February 1996
Cyclic Estradiol Treatment Normalizes Body Weight and Test Meal Size in Ovariectomized Rats Geary, Nori; Asarian, Lori Physiology & Behavior, Vol. 67, Issue 1 https://doi.org/10.1016/S0031-9384(99)00060-8	journal	August 1999
Estradiol, CCK and satiation Geary, Nori Peptides, Vol. 22, Issue 8 https://doi.org/10.1016/S0196-9781(01)00449-1	journal	August 2001
Cortical and limbic activation during viewing of high- versus low-calorie foods Killgore, William D. S.; Young, Ashley D.; Femia, Lisa A. NeuroImage, Vol. 19, Issue 4 https://doi.org/10.1016/S1053-8119(03)00191-5	journal	August 2003
Effect of the cytochrome P450 19 (aromatase) gene polymorphism on personality traits in healthy subjects Matsumoto, Yoshihiko; Suzuki, Akihito; Shibuya, Naoshi Behavioural Brain Research, Vol. 205, Issue 1 https://doi.org/10.1016/j.bbr.2009.06.034	journal	December 2009
Effects of chronic testosterone administration on body weight and food intake differ among pre-pubertal, gonadal-intact, and ovariectomized female rats Iwasa, Takeshi; Matsuzaki, Toshiya; Tungalagsuvd, Altankhuu Behavioural Brain Research, Vol. 309 https://doi.org/10.1016/j.bbr.2016.04.048	journal	August 2016
The worldwide epidemic of female obesity Mitchell, Sheona; Shaw, Dorothy Best Practice & Research Clinical Obstetrics & Gynaecology, Vol. 29, Issue 3 https://doi.org/10.1016/j.bpobgyn.2014.10.002	journal	April 2015
The Obesity Epidemic Catenacci, Victoria A.; Hill, James O.; Wyatt, Holly R. Clinics in Chest Medicine, Vol. 30, Issue 3 https://doi.org/10.1016/j.ccm.2009.05.001	journal	September 2009
Medial Amygdalar Aromatase Neurons Regulate Aggression in Both Sexes Unger, Elizabeth K.; Burke, Kenneth J.; Yang, Cindy F. Cell Reports, Vol. 10, Issue 4 https://doi.org/10.1016/j.celrep.2014.12.040	journal	February 2015
Conceptualizing the role of estrogens and serotonin in the development and maintenance of bulimia nervosa Hildebrandt, Tom; Alfano, Lauren; Tricamo, Michelle Clinical Psychology Review, Vol. 30, Issue 6 https://doi.org/10.1016/j.cpr.2010.04.011	journal	August 2010
The sexually dimorphic role of adipose and adipocyte estrogen receptors in modulating adipose tissue expansion, inflammation, and fibrosis Davis, Kathryn E.; D. Neinast, Michael; Sun, Kai Molecular Metabolism, Vol. 2, Issue 3 https://doi.org/10.1016/j.molmet.2013.05.006	journal	August 2013
Neural correlates of personality: An integrative review Kennis, Mitzy; Rademaker, Arthur R.; Geuze, Elbert Neuroscience & Biobehavioral Reviews, Vol. 37, Issue 1 https://doi.org/10.1016/j.neubiorev.2012.10.012	journal	January 2013
Differential activation of the dorsal striatum by high-calorie visual food stimuli in obese individuals Rothemund, Yvonne; Preuschhof, Claudia; Bohner, Georg NeuroImage, Vol. 37, Issue 2 https://doi.org/10.1016/j.neuroimage.2007.05.008	journal	August 2007
Effects of letrozole on hippocampal and cortical catecholaminergic neurotransmitter levels, neural cell adhesion molecule expression and spatial learning and memory in female rats Aydin, M.; Yilmaz, B.; Alcin, E. Neuroscience, Vol. 151, Issue 1 https://doi.org/10.1016/j.neuroscience.2007.09.005	journal	January 2008
Obesity and Eating Disorders Allison, Kelly C.; Stunkard, Albert J. Psychiatric Clinics of North America, Vol. 28, Issue 1 https://doi.org/10.1016/j.psc.2004.09.006	journal	March 2005
Estrogenic encounters: How interactions between aromatase and the environment modulate aggression Trainor, B.; Kyomen, H.; Marler, C. Frontiers in Neuroendocrinology, Vol. 27, Issue 2 https://doi.org/10.1016/j.yfrne.2005.11.001	journal	July 2006
In vivo visualization of aromatase in animals and humans Biegon, Anat Frontiers in Neuroendocrinology, Vol. 40 https://doi.org/10.1016/j.yfrne.2015.10.001	journal	January 2016
Estradiol and cognitive function: Past, present and future Luine, Victoria N. Hormones and Behavior, Vol. 66, Issue 4 https://doi.org/10.1016/j.yhbeh.2014.08.011	journal	September 2014
Neurocognitive effects of estrogens across the adult lifespan in nonhuman primates: State of knowledge and new perspectives Lacreuse, Agnès; Mong, Jessica A.; Hara, Yuko Hormones and Behavior, Vol. 74 https://doi.org/10.1016/j.yhbeh.2015.03.001	journal	August 2015
Ovarian hormone fluctuations predict within-cycle shifts in women's food intake Roney, James R.; Simmons, Zachary L. Hormones and Behavior, Vol. 90 https://doi.org/10.1016/j.yhbeh.2017.01.009	journal	April 2017
Hunger selectively modulates corticolimbic activation to food stimuli in humans. LaBar, Kevin S.; Gitelman, Darren R.; Parrish, Todd B. Behavioral Neuroscience, Vol. 115, Issue 2 https://doi.org/10.1037/0735-7044.115.2.493	journal	January 2001
Altered food preferences after lesions in the basolateral region of the amygdala in the rat. Rolls, Edmund T.; Rolls, Barbara J. Journal of Comparative and Physiological Psychology, Vol. 83, Issue 2 https://doi.org/10.1037/h0034414	journal	May 1973
Opposing roles for amygdala and vmPFC in the return of appetitive conditioned responses in humans Ebrahimi, Claudia; Koch, Stefan P.; Pietrock, Charlotte Translational Psychiatry, Vol. 9, Issue 1 https://doi.org/10.1038/s41398-019-0482-x	journal	May 2019
Association between aromatase in human brains and personality traits Takahashi, Kayo; Hosoya, Takamitsu; Onoe, Kayo Scientific Reports, Vol. 8, Issue 1 https://doi.org/10.1038/s41598-018-35065-4	journal	November 2018
Estrogen Promotes Stress Sensitivity in a Prefrontal Cortex-Amygdala Pathway Shansky, R. M.; Hamo, C.; Hof, P. R. Cerebral Cortex, Vol. 20, Issue 11 https://doi.org/10.1093/cercor/bhq003	journal	February 2010
Ovarian hormones and obesity Leeners, Brigitte; Geary, Nori; Tobler, Philippe N. Human Reproduction Update, Vol. 23, Issue 3 https://doi.org/10.1093/humupd/dmw045	journal	March 2017
Extragonadal synthesis of estradiol is protective against kainic acid excitotoxic damage to the hippocampus Veiga, Sergio; Azcoitia, I??igo; Garcia-Segura, Luis M. NeuroReport, Vol. 16, Issue 14 https://doi.org/10.1097/01.wnr.0000179081.39659.7d	journal	January 2005
Gonadal hormone contributions to individual differences in eating disorder risk Mikhail, Megan E.; Culbert, Kristen M.; Sisk, Cheryl L. Current Opinion in Psychiatry, Vol. 32, Issue 6 https://doi.org/10.1097/YCO.0000000000000543	journal	January 2019
Modulation of appetite by gonadal steroid hormones Asarian, Lori; Geary, Nori Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 361, Issue 1471 https://doi.org/10.1098/rstb.2006.1860	journal	June 2006
The obesity epidemic: time for the Government ‘heavies’ to step in? Datta, S. BJOG: An International Journal of Obstetrics & Gynaecology, Vol. 123, Issue 2 https://doi.org/10.1111/1471-0528.13714	journal	November 2015
Amygdala Subsystems and Control of Feeding Behavior by Learned Cues Petrovich, Gorica D.; Gallagher, Michela Annals of the New York Academy of Sciences, Vol. 985, Issue 1 https://doi.org/10.1111/j.1749-6632.2003.tb07086.x	journal	April 2003
Hypothalamic Expression of Oestrogen Receptor α and Androgen Receptor is Sex-, Age- and Region-Dependent in Mice Brock, O.; De Mees, C.; Bakker, J. Journal of Neuroendocrinology, Vol. 27, Issue 4 https://doi.org/10.1111/jne.12258	journal	March 2015
Posterodorsal Medial Amygdala Mediates Tail-Pinch Induced Food Intake in Female Rats Hu, M. H.; Bashir, Z.; Li, X. F. Journal of Neuroendocrinology, Vol. 28, Issue 5 https://doi.org/10.1111/jne.12390	journal	May 2016
Effectiveness of weight loss interventions - is there a difference between men and women: a systematic review: Sex differences in men and women Williams, R. L.; Wood, L. G.; Collins, C. E. Obesity Reviews, Vol. 16, Issue 2 https://doi.org/10.1111/obr.12241	journal	December 2014
Personality Processes: Mechanisms by Which Personality Traits “Get Outside the Skin” Hampson, Sarah E. Annual Review of Psychology, Vol. 63, Issue 1 https://doi.org/10.1146/annurev-psych-120710-100419	journal	January 2012
The Response of the US Centers for Disease Control and Prevention to the Obesity Epidemic Dietz, William H. Annual Review of Public Health, Vol. 36, Issue 1 https://doi.org/10.1146/annurev-publhealth-031914-122415	journal	March 2015
Acute activation of ERα decreases food intake, meal size, and body weight in ovariectomized rats Santollo, Jessica; Wiley, Mathew D.; Eckel, Lisa A. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Vol. 293, Issue 6 https://doi.org/10.1152/ajpregu.00385.2007	journal	December 2007
Sex differences in the physiology of eating Asarian, Lori; Geary, Nori American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Vol. 305, Issue 11 https://doi.org/10.1152/ajpregu.00446.2012	journal	December 2013
Aromatase: Contributions to Physiology and Disease in Women and Men Blakemore, Jennifer; Naftolin, Fredrick Physiology, Vol. 31, Issue 4 https://doi.org/10.1152/physiol.00054.2015	journal	July 2016
Present and Future: Pharmacologic Treatment of Obesity Glandt, Mariela; Raz, Itamar Journal of Obesity, Vol. 2011 https://doi.org/10.1155/2011/636181	journal	January 2011
Aromatase Immunoreactivity in Axon Terminals of the Vertebrate Brain Naftolin, Frederick; Horvath, Tamas L.; Jakab, Robert L. Neuroendocrinology, Vol. 63, Issue 2 https://doi.org/10.1159/000126951	journal	January 1996
Effect of Estrogen-Serotonin Interactions on Mood and Cognition Amin, Zenab; Canli, Turhan; Epperson, C. Neill Behavioral and Cognitive Neuroscience Reviews, Vol. 4, Issue 1 https://doi.org/10.1177/1534582305277152	journal	March 2005
Impulse and Constraint: Perspectives From Personality Psychology, Convergence With Theory in Other Areas, and Potential for Integration Carver, Charles S. Personality and Social Psychology Review, Vol. 9, Issue 4 https://doi.org/10.1207/s15327957pspr0904_2	journal	November 2005
Activation of Central, But Not Peripheral, Estrogen Receptors Is Necessary for Estradiol’s Anorexigenic Effect in Ovariectomized Rats Rivera, Heidi M.; Eckel, Lisa A. Endocrinology, Vol. 151, Issue 12 https://doi.org/10.1210/en.2010-0731	journal	November 2010
Exercise and Weight Loss: No Sex Differences in Body Weight Response to Exercise Caudwell, Phillipa; Gibbons, Catherine; Finlayson, Graham Exercise and Sport Sciences Reviews, Vol. 42, Issue 3 https://doi.org/10.1249/JES.0000000000000019	journal	January 2014
Evidence Supporting the Need for Bariatric Surgery to Address the Obesity Epidemic in the United States Bour, Eric S. Current Sports Medicine Reports, Vol. 14, Issue 2 https://doi.org/10.1249/JSR.0000000000000135	journal	January 2015
Achievement of weight loss in patients with overweight during dietetic treatment in primary health care Verberne, Lisa D. M.; Leemrijse, Chantal J.; Nielen, Markus M. J. PLOS ONE, Vol. 14, Issue 11 https://doi.org/10.1371/journal.pone.0225065	journal	November 2019
Individual Differences in Reward Drive Predict Neural Responses to Images of Food Beaver, J. D. Journal of Neuroscience, Vol. 26, Issue 19 https://doi.org/10.1523/JNEUROSCI.0350-06.2006	journal	May 2006
Involvement of Human Amygdala and Orbitofrontal Cortex in Hunger-Enhanced Memory for Food Stimuli Morris, J. S.; Dolan, R. J. The Journal of Neuroscience, Vol. 21, Issue 14 https://doi.org/10.1523/JNEUROSCI.21-14-05304.2001	journal	July 2001
Amygdalar and Prefrontal Pathways to the Lateral Hypothalamus Are Activated by a Learned Cue That Stimulates Eating Petrovich, G. D. Journal of Neuroscience, Vol. 25, Issue 36 https://doi.org/10.1523/JNEUROSCI.2480-05.2005	journal	September 2005
Central, But Not Basolateral, Amygdala Is Critical for Control of Feeding by Aversive Learned Cues Petrovich, G. D.; Ross, C. A.; Mody, P. Journal of Neuroscience, Vol. 29, Issue 48 https://doi.org/10.1523/JNEUROSCI.3656-09.2009	journal	December 2009
Aromatization of Androstenedione by Limbic System Tissue from Human Foetuses Naftolin, F.; Ryan, K. J.; Petro, Z. Journal of Endocrinology, Vol. 51, Issue 4 https://doi.org/10.1677/joe.0.0510795	journal	December 1971
In Vivo Imaging of Brain Aromatase in Female Baboons: [ ¹¹ C]Vorozole Kinetics and Effect of the Menstrual Cycle Pareto, Deborah; Biegon, Anat; Alexoff, David Molecular Imaging, Vol. 12, Issue 8 https://doi.org/10.2310/7290.2013.00068	journal	November 2013
Kinetic Analysis of [ ¹¹ C]Vorozole Binding in the Human Brain with Positron Emission Tomography Logan, Jean; Kim, Sung Won; Pareto, Deborah Molecular Imaging, Vol. 13, Issue 3 https://doi.org/10.2310/7290.2014.00004	journal	May 2014
Initial Studies with ¹¹ C-Vorozole PET Detect Overexpression of Intratumoral Aromatase in Breast Cancer Biegon, Anat; Shroyer, Kenneth R.; Franceschi, Dinko Journal of Nuclear Medicine, Vol. 61, Issue 6 https://doi.org/10.2967/jnumed.119.231589	journal	November 2019
Systematic review of the long-term effects and economic consequences of treatments for obesity and implications for health improvement Avenell, A.; Broom, J.; Brown, T. Health Technology Assessment, Vol. 8, Issue 21 https://doi.org/10.3310/hta8210	journal	May 2004
The Moderating Role of Self-Control and Financial Strain in the Relation between Exposure to the Food Environment and Obesity: The GLOBE Study Mackenbach, Joreintje; Beenackers, Marielle; Noordzij, J. International Journal of Environmental Research and Public Health, Vol. 16, Issue 4 https://doi.org/10.3390/ijerph16040674	journal	February 2019

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