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Pais ML, Crisóstomo J, Abrunhosa A, Castelo-Branco M. Central dopamine receptors: Radiotracers unveiling the Role of dopaminergic tone in obesity. J Mol Med (Berl) 2025; 103:21-32. [PMID: 39630278 PMCID: PMC11739276 DOI: 10.1007/s00109-024-02501-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 10/05/2024] [Accepted: 11/04/2024] [Indexed: 01/19/2025]
Abstract
Brain dopamine type 2 and 3 receptors (D2/3R) have been postulated to play a role in obesity. However, results from molecular neuroimaging studies exploring these receptors in obesity are not consensual. These inconsistencies may be due to the distinct characteristics of radiotracers that confound the interpretation of D2/3R assessment. Only three meta-analyses reported their results across radiotracers. Although all agree that obesity severity influences D2/3R availability, results vary for [11C]raclopride. Further, D2/3R assessment has been commonly interpreted as reflecting receptor density or availability. An alternative interpretation could be related to changes in endogenous central dopaminergic tone. The main question is whether the hypothesis of a quadratic relationship between dopaminergic tone and degree of obesity is suitable for the distinct characteristics of radiotracers. To answer this question and clarify the role of dopaminergic tone in obesity, we systematically reviewed this issue across radiotracers. Out of 514 articles, 15 articles were selected for review. Besides obesity severity, this study highlights the influence of radiotracer characteristics when assessing D2/3R. The tested hypothesis proved to be more suitable for radiotracers more susceptible to endogenous dopamine or with a lower affinity to D2/3R, supporting the quadratic relationship between dopaminergic tone and degree of obesity. While the role of D2/3R density in obesity may be relevant, dopaminergic tone seems to have a greater impact on the obesity-related differences found in these receptors. Finally, neuropsychological factors should be tested in addition to body mass index, as they may better reflect altered brain dopaminergic function.
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Affiliation(s)
- Marta Lapo Pais
- Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, Coimbra, Portugal
- Institute for Nuclear Sciences Applied to Health (ICNAS), University of Coimbra, Coimbra, Portugal
- Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal
| | - Joana Crisóstomo
- Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, Coimbra, Portugal
- Champalimaud Research, Champalimaud Foundation, Lisbon, Portugal
| | - Antero Abrunhosa
- Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, Coimbra, Portugal
- Institute for Nuclear Sciences Applied to Health (ICNAS), University of Coimbra, Coimbra, Portugal
| | - Miguel Castelo-Branco
- Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, Coimbra, Portugal.
- Institute for Nuclear Sciences Applied to Health (ICNAS), University of Coimbra, Coimbra, Portugal.
- Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
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Gumede NAC, Khathi A. The Role of Pro-Opiomelanocortin Derivatives in the Development of Type 2 Diabetes-Associated Myocardial Infarction: Possible Links with Prediabetes. Biomedicines 2024; 12:314. [PMID: 38397916 PMCID: PMC10887103 DOI: 10.3390/biomedicines12020314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 01/14/2024] [Accepted: 01/23/2024] [Indexed: 02/25/2024] Open
Abstract
Myocardial infarction is a major contributor to CVD-related mortality. T2DM is a risk factor for MI. Stress activates the HPA axis, SNS, and endogenous OPS. These POMC derivatives increase the blood glucose and cardiovascular response by inhibiting the PI3K/AkT insulin signaling pathway and increasing cardiac contraction. Opioids regulate the effect of the HPA axis and SNS and they are cardioprotective. The chronic activation of the stress response may lead to insulin resistance, cardiac dysfunction, and MI. Stress and T2DM, therefore, increase the risk of MI. T2DM is preceded by prediabetes. Studies have shown that prediabetes is associated with an increased risk of MI because of inflammation, hyperlipidemia, endothelial dysfunction, and hypertension. The HPA axis is reported to be dysregulated in prediabetes. However, the SNS and the OPS have not been explored during prediabetes. The effect of prediabetes on POMC derivatives has yet to be fully explored and understood. The impact of stress and prediabetes on the cardiovascular response needs to be investigated. This study sought to review the potential impact of prediabetes on the POMC derivatives and pathways that could lead to MI.
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Affiliation(s)
- Nompumelelo Anna-Cletta Gumede
- Department of Human Physiology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban X54001, South Africa;
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Sayar-Atasoy N, Yavuz Y, Laule C, Dong C, Kim H, Rysted J, Flippo K, Davis D, Aklan I, Yilmaz B, Tian L, Atasoy D. Opioidergic signaling contributes to food-mediated suppression of AgRP neurons. Cell Rep 2024; 43:113630. [PMID: 38165803 PMCID: PMC10865729 DOI: 10.1016/j.celrep.2023.113630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 11/22/2023] [Accepted: 12/13/2023] [Indexed: 01/04/2024] Open
Abstract
Opioids are generally known to promote hedonic food consumption. Although much of the existing evidence is primarily based on studies of the mesolimbic pathway, endogenous opioids and their receptors are widely expressed in hypothalamic appetite circuits as well; however, their role in homeostatic feeding remains unclear. Using a fluorescent opioid sensor, deltaLight, here we report that mediobasal hypothalamic opioid levels increase by feeding, which directly and indirectly inhibits agouti-related protein (AgRP)-expressing neurons through the μ-opioid receptor (MOR). AgRP-specific MOR expression increases by energy surfeit and contributes to opioid-induced suppression of appetite. Conversely, its antagonists diminish suppression of AgRP neuron activity by food and satiety hormones. Mice with AgRP neuron-specific ablation of MOR expression have increased fat preference without increased motivation. These results suggest that post-ingestion release of endogenous opioids contributes to AgRP neuron inhibition to shape food choice through MOR signaling.
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Affiliation(s)
- Nilufer Sayar-Atasoy
- Department of Neuroscience and Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
| | - Yavuz Yavuz
- Department of Neuroscience and Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Department of Physiology, School of Medicine, Yeditepe University, Istanbul 34755, Turkey
| | - Connor Laule
- Department of Neuroscience and Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
| | - Chunyang Dong
- Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, Davis, CA 95616, USA
| | - Hyojin Kim
- Department of Neuroscience and Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
| | - Jacob Rysted
- Department of Neuroscience and Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
| | - Kyle Flippo
- Department of Neuroscience and Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
| | - Debbie Davis
- Department of Neuroscience and Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
| | - Iltan Aklan
- Department of Neuroscience and Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
| | - Bayram Yilmaz
- Department of Physiology, School of Medicine, Yeditepe University, Istanbul 34755, Turkey
| | - Lin Tian
- Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, Davis, CA 95616, USA
| | - Deniz Atasoy
- Department of Neuroscience and Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Iowa Neuroscience Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Fraternal Order of Eagles Diabetes Research Center (FOEDRC), Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
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Flores MR, Zuniga SS. Integration of Endogenous Opioid System Research in the Interprofessional Diagnosis and Treatment of Obesity and Eating Disorders. ADVANCES IN NEUROBIOLOGY 2024; 35:357-380. [PMID: 38874732 DOI: 10.1007/978-3-031-45493-6_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2024]
Abstract
This third and final chapter in our trilogy introduces the clinical distinctions and phenotypical similarities between obesity and eating disorders. Research elaborating on the shared neurobiological substrates for obesity and eating disorders is discussed. We present an interprofessional model of treatment for both disordered eating and for obesity. Additionally, this chapter establishes the translational importance of research connecting endogenous opioid activity with both obesity and eating disorders, with an emphasis on clinical interventions. We conclude with a discussion of future directions for research.
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Affiliation(s)
| | - Sylvana Stephano Zuniga
- Obesity and Eating Disorders Clinic, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico
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Pak K, Nummenmaa L. Brain dopamine receptor system is not altered in obesity: Bayesian and frequentist meta-analyses. Hum Brain Mapp 2023; 44:6552-6560. [PMID: 37950852 PMCID: PMC10681634 DOI: 10.1002/hbm.26534] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Revised: 10/23/2023] [Accepted: 10/30/2023] [Indexed: 11/13/2023] Open
Abstract
Feeding induces dopamine release in the striatum, and a dysfunction of the dopaminergic reward system can lead to overeating, and obesity. Studies have reported inconsistent findings of dopamine receptor (DR) positron emission tomography scans in obesity. Here we investigated the association between DR availability and overweight/obesity using Bayesian and frequentist meta-analysis. We performed a systematic search of Embase, Medline, Scopus and Web of Science for studies that compared striatal DR availability between lean subjects and overweight/obese subjects. The standardized mean difference (Hedge's g) of DR availability was calculated after extraction of data from each study. Studies were divided into two groups according to the definition of overweight/obese subjects (body mass index [BMI] cutoff of 25 and 30 kg/m2 ). Both Bayesian and frequentist meta-analysis was done in R Statistical Software version 4.2.2 (The R Foundation for Statistical Computing). Nine studies were eligible for inclusion in this study. Three studies with C11-raclopride, one with C11-PNHO, two with F18-fallypride, one with I123-IBZM, one with C11-NMB and one with both C11-raclopride and C11-PNHO were included. In Bayesian meta-analysis, the standardized mean difference of DR availability between lean and overweight/obese subjects markedly overlapped with zero regardless of BMI cutoff for obesity. In frequentist meta-analysis, the pooled standardized mean difference of DR availability did not show the significant difference between lean and overweight/obese subjects. There was an effect of the radiopharmaceutical on the standardized mean difference of DR availability in meta-analysis of BMI cutoff of 25 kg/m2 . In conclusion, brain DR availability is not different between lean and overweight/obese subjects. However, the effect is dependent on the radiopharmaceutical and the degree of obesity. Further studies with multi-radiopharmaceutical in the same individuals are needed to understand the association between DR and obesity.
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Affiliation(s)
- Kyoungjune Pak
- Department of Nuclear Medicine and Biomedical Research InstitutePusan National University HospitalBusanRepublic of Korea
- School of MedicinePusan National UniversityBusanRepublic of Korea
| | - Lauri Nummenmaa
- Turku PET CentreUniversity of TurkuTurkuFinland
- Turku PET CentreTurku University HospitalTurkuFinland
- Department of PsychologyUniversity of TurkuTurkuFinland
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Al‐Alsheikh AS, Alabdulkader S, Miras AD, Goldstone AP. Effects of bariatric surgery and dietary interventions for obesity on brain neurotransmitter systems and metabolism: A systematic review of positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies. Obes Rev 2023; 24:e13620. [PMID: 37699864 PMCID: PMC10909448 DOI: 10.1111/obr.13620] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Revised: 04/05/2023] [Accepted: 07/10/2023] [Indexed: 09/14/2023]
Abstract
This systematic review collates studies of dietary or bariatric surgery interventions for obesity using positron emission tomography and single-photon emission computed tomography. Of 604 publications identified, 22 met inclusion criteria. Twelve studies assessed bariatric surgery (seven gastric bypass, five gastric bypass/sleeve gastrectomy), and ten dietary interventions (six low-calorie diet, three very low-calorie diet, one prolonged fasting). Thirteen studies examined neurotransmitter systems (six used tracers for dopamine DRD2/3 receptors: two each for 11 C-raclopride, 18 F-fallypride, 123 I-IBZM; one for dopamine transporter, 123 I-FP-CIT; one used tracer for serotonin 5-HT2A receptor, 18 F-altanserin; two used tracers for serotonin transporter, 11 C-DASB or 123 I-FP-CIT; two used tracer for μ-opioid receptor, 11 C-carfentanil; one used tracer for noradrenaline transporter, 11 C-MRB); seven studies assessed glucose uptake using 18 F-fluorodeoxyglucose; four studies assessed regional cerebral blood flow using 15 O-H2 O (one study also used arterial spin labeling); and two studies measured fatty acid uptake using 18 F-FTHA and one using 11 C-palmitate. The review summarizes findings and correlations with clinical outcomes, eating behavior, and mechanistic mediators. The small number of studies using each tracer and intervention, lack of dietary intervention control groups in any surgical studies, heterogeneity in time since intervention and degree of weight loss, and small sample sizes hindered the drawing of robust conclusions across studies.
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Affiliation(s)
- Alhanouf S. Al‐Alsheikh
- Department of Metabolism, Digestion and Reproduction, Imperial College LondonHammersmith HospitalLondonUK
- Department of Community Health Sciences, College of Applied Medical SciencesKing Saud UniversityRiyadhSaudi Arabia
| | - Shahd Alabdulkader
- Department of Metabolism, Digestion and Reproduction, Imperial College LondonHammersmith HospitalLondonUK
- Department of Health Sciences, College of Health and Rehabilitation SciencesPrincess Nourah Bint Abdulrahman UniversityRiyadhSaudi Arabia
| | - Alexander D. Miras
- Department of Metabolism, Digestion and Reproduction, Imperial College LondonHammersmith HospitalLondonUK
- School of Medicine, Faculty of Life and Health SciencesUlster UniversityLondonderryUK
| | - Anthony P. Goldstone
- PsychoNeuroEndocrinology Research Group, Division of Psychiatry, Department of Brain Sciences, Imperial College LondonHammersmith HospitalLondonUK
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Huerta-Canseco C, Caba M, Camacho-Morales A. Obesity-mediated Lipoinflammation Modulates Food Reward Responses. Neuroscience 2023; 529:37-53. [PMID: 37591331 DOI: 10.1016/j.neuroscience.2023.08.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 08/07/2023] [Accepted: 08/09/2023] [Indexed: 08/19/2023]
Abstract
Accumulation of white adipose tissue (WAT) during obesity is associated with the development of chronic low-grade inflammation, a biological process known as lipoinflammation. Systemic and central lipoinflammation accumulates pro-inflammatory cytokines including IL-6, IL-1β and TNF-α in plasma and also in brain, disrupting neurometabolism and cognitive behavior. Obesity-mediated lipoinflammation has been reported in brain regions of the mesocorticolimbic reward circuit leading to alterations in the perception and consumption of ultra-processed foods. While still under investigation, lipoinflammation targets two major outcomes of the mesocorticolimbic circuit during food reward: perception and motivation ("Wanting") and the pleasurable feeling of feeding ("Liking"). This review will provide experimental and clinical evidence supporting the contribution of obesity- or overnutrition-related lipoinflammation affecting the mesocorticolimbic reward circuit and enhancing food reward responses. We will also address neuroanatomical targets of inflammatory profiles that modulate food reward responses during obesity and describe potential cellular and molecular mechanisms of overnutrition linked to addiction-like behavior favored by brain lipoinflammation.
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Affiliation(s)
| | - Mario Caba
- Centro de Investigaciones Biomédicas, Universidad Veracruzana, Xalapa, Mexico
| | - Alberto Camacho-Morales
- Department of Biochemistry, College of Medicine, Universidad Autónoma de Nuevo León, Monterrey, NL, Mexico; Neurometabolism Unit, Center for Research and Development in Health Sciences, Universidad Autónoma de Nuevo León, Monterrey, NL, Mexico.
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Wuyts SCM, Torensma B, Schellekens AFA, Kramers C(K. Opioid Analgesics after Bariatric Surgery: A Scoping Review to Evaluate Physiological Risk Factors for Opioid-Related Harm. J Clin Med 2023; 12:4296. [PMID: 37445331 PMCID: PMC10342511 DOI: 10.3390/jcm12134296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Revised: 06/20/2023] [Accepted: 06/25/2023] [Indexed: 07/15/2023] Open
Abstract
The persisting use of opioids following bariatric surgery has emerged as a prevalent complication, heightening the probability of opioid-related harm (ORM), such as opioid-related fatalities and prescription opioid use disorder (OUD). A comprehensive review of PubMed literature from 1990 to 2023 was conducted to pinpoint physiological influences on postoperative ORM. As a result, we found that patients undertaking bariatric operations often exhibit an inherently higher risk for substance use disorders, likely attributable to genetic predisposition and related neurobiological changes that engender obesity and addiction-like tendencies. Furthermore, chronic pain is a common post-bariatric surgery complaint, and the surgical type impacts opioid needs, with increased long-term opioid use after surgeries. Additionally, the subjective nature of pain perception in patients with obesity can distort pain reporting and the corresponding opioid prescription both before and after surgery. Furthermore, the postoperative alterations to the gastrointestinal structure can affect the microbiome and opioid absorption rates, resulting in fluctuating systemic exposure to orally ingested opioids. The prospect of ORM development post-bariatric surgery appears amplified due to a preexisting susceptibility to addictive habits, surgically induced pain, modified gut-brain interaction and pain management and the changed pharmacokinetics post-surgery. Further research is warranted to clarify these potential risk variables for ORM, specifically OUD, in the bariatric population.
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Affiliation(s)
- Stephanie C. M. Wuyts
- Pharmacy Department, Universitair Ziekenhuis Brussel (UZ Brussel), 1090 Brussels, Belgium
- Research Group Clinical Pharmacology and Clinical Pharmacy, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, 1090 Brussels, Belgium
| | - Bart Torensma
- Department of Anesthesiology, Leiden University Medical Center (LUMC), 2333 ZA Leiden, The Netherlands;
| | - Arnt F. A. Schellekens
- Department of Psychiatry, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands;
| | - Cornelis (Kees) Kramers
- Department of Internal Medicine and Pharmacology-Toxicology, Radboud University Nijmegen Medical Center, 6525 GA Nijmegen, The Netherlands;
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Lammert M, Medawar E, Hartmann H, Grasser L, Dietrich A, Fenske W, Horstmann A. Distinct adaptations of endocrine and cognitive functions may contribute to high variability in long-term weight loss outcome after bariatric surgery. Physiol Behav 2023:114279. [PMID: 37356514 DOI: 10.1016/j.physbeh.2023.114279] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 05/08/2023] [Accepted: 06/20/2023] [Indexed: 06/27/2023]
Abstract
BACKGROUND Bariatric surgery has been widely recognized as the most efficient long-term treatment method in severe obesity, yet therapy success shows considerable interindividual variability. Postoperative metabolic adaptations, including improved gut hormone secretion (GLP-1, PYY and ghrelin), and restored executive function may play an explanatory role in weight loss, yet causes for poor success in individual patients remain unknown. This study investigates gut-hormonal and cognitive characteristics in extreme weight loss responders to bariatric surgery. METHODS Patients (n=47) with high or low excessive weight loss (EWL) at least 2 years after Roux-en-Y-gastric bypass or sleeve gastrectomy were allocated into good responders (GR, EWL 82.4 ± 11.6%) and poor responders (PR, EWL 24.0 ± SD 12.8%) to study differences in postprandial secretion of GLP-1, PYY, ghrelin and in working memory (WM). RESULTS Mean BMI was 47.1 ± 6.2 kg/m² in PR (n=21) and 28.9 ± 3.1 kg/m² in GR (n=26, p < 0.001). Fasted GLP-1 and PYY were comparable for GR and PR (p > 0.2) and increased strongly after a standardized test meal (300 kcal liquid meal) with a peak at 15 to 30 minutes. The increase was stronger in GR compared to PR (GLP-1, PYY: Time x Group p < 0.05). Plasma ghrelin levels already differed between groups at fasted state, showing significantly higher levels for GR (p < 0.05). Postprandially, ghrelin secretion was suppressed in both groups, but suppression was higher in GR (Time x Group p < 0.05). GR showed significantly higher WM scores than PR (p < 0.05). Postprandial ghrelin (iAUC), but not GLP-1 or PYY plasma levels, significantly mediated the relationship between EWL and a WM subscore (IS score, CI = 0.07 - 1.68), but not WM main score (MIS score, CI = -0.07 - 1.54), in mediation analyses. CONCLUSION Excess weight loss success after bariatric surgical procedures is associated with distinct profiles of gut-hormones at fasted and postprandial state, and differences in working memory. Better working memory performance in GR might be mediated by higher postprandial reduction in ghrelin plasma levels. Future studies need to integrate longitudinal data, larger samples and more sensitive cognitive tests.
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Affiliation(s)
- Mathis Lammert
- Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany; Leipzig University Medical Centre, IFB Adiposity Diseases, 04103 Leipzig, Germany; Leipzig University Medical Centre, Collaborative Research Centre 1052-A5, 04103 Leipzig, Germany.
| | - Evelyn Medawar
- Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany.
| | - Hendrik Hartmann
- Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany; Leipzig University Medical Centre, Collaborative Research Centre 1052-A5, 04103 Leipzig, Germany; Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland.
| | - Linda Grasser
- Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany; Leipzig University Medical Centre, IFB Adiposity Diseases, 04103 Leipzig, Germany.
| | - Arne Dietrich
- Department of Obesity, Metabolic and Endocrine Surgery, University Hospital Leipzig, Liebigstraße 18, 04103 Leipzig, Germany.
| | - Wiebke Fenske
- Department of Endocrinology, Diabetes and Metabolism, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany.
| | - Annette Horstmann
- Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany; Leipzig University Medical Centre, IFB Adiposity Diseases, 04103 Leipzig, Germany; Leipzig University Medical Centre, Collaborative Research Centre 1052-A5, 04103 Leipzig, Germany; Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland.
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Li ZA, Cai Y, Taylor RL, Eisenstein SA, Barch DM, Marek S, Hershey T. Associations between socioeconomic status and white matter microstructure in children: indirect effects via obesity and cognition. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2023:2023.02.09.23285150. [PMID: 36798149 PMCID: PMC9934783 DOI: 10.1101/2023.02.09.23285150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/12/2023]
Abstract
Importance Both neighborhood and household socioeconomic disadvantage relate to negative health outcomes and altered brain structure in children. It is unclear whether such findings extend to white matter development, and via what mechanisms socioeconomic status (SES) influences the brain. Objective To test independent associations between neighborhood and household SES indicators and white matter microstructure in children, and examine whether body mass index and cognitive function (a proxy of environmental cognitive/sensory stimulation) may plausibly mediate these associations. Design This cross-sectional study used baseline data from the Adolescent Brain Cognitive Development (ABCD) Study, an ongoing 10-year cohort study tracking child health. Setting School-based recruitment at 21 U.S. sites. Participants Children aged 9 to 11 years and their parents/caregivers completed baseline assessments between October 1 st , 2016 and October 31 st , 2018. Data analysis was conducted from July to December 2022. Exposures Neighborhood disadvantage was derived from area deprivation indices at primary residence. Household SES indicators were total income and the highest parental education attainment. Main Outcomes and Measures Thirty-one major white matter tracts were segmented from diffusion-weighted images. The Restriction Spectrum Imaging (RSI) model was implemented to measure restricted normalized directional (RND; reflecting oriented myelin organization) and isotropic (RNI; reflecting glial/neuronal cell bodies) diffusion in each tract. Obesity-related measures were body mass index (BMI), BMI z -scores, and waist circumference, and cognitive performance was assessed using the NIH Toolbox Cognition Battery. Linear mixed-effects models tested the associations between SES indicators and scanner-harmonized RSI metrics. Structural equation models examined indirect effects of obesity and cognitive performance in the significant associations between SES and white mater microstructure summary principal components. Analyses were adjusted for age, sex, pubertal development stage, intracranial volume, and head motion. Results The analytical sample included 8842 children (4299 [48.6%] girls; mean age [SD], 9.9 [0.7] years). Greater neighborhood disadvantage and lower parental education were independently associated with lower RSI-RND in forceps major and corticospinal/pyramidal tracts, and had overlapping associations in the superior longitudinal fasciculus. Lower cognition scores and greater obesity-related measures partially accounted for these SES associations with RSI-RND. Lower household income was related to higher RSI-RNI in almost every tract, and greater neighborhood disadvantage had similar effects in primarily frontolimbic tracts. Lower parental education was uniquely linked to higher RSI-RNI in forceps major. Greater obesity-related measures partially accounted for these SES associations with RSI-RNI. Findings were robust in sensitivity analyses and mostly corroborated using traditional diffusion tensor imaging (DTI). Conclusions and Relevance These cross-sectional results demonstrate that both neighborhood and household contexts are relevant to white matter development in children, and suggest cognitive performance and obesity as possible pathways of influence. Interventions targeting obesity reduction and improving cognition from multiple socioeconomic angles may ameliorate brain health in low-SES children. Key Points Question: Are neighborhood and household socioeconomic levels associated with children’s brain white matter microstructure, and if so, do obesity and cognitive performance (reflecting environmental stimulation) mediate the associations?Findings: In a cohort of 8842 children, higher neighborhood disadvantage, lower household income, and lower parental education had independent and overlapping associations with lower restricted directional diffusion and greater restricted isotropic diffusion in white matter. Greater body mass index and poorer cognitive performance partially mediated these associations.Meaning: Both neighborhood and household poverty may contribute to altered white matter development in children. These effects may be partially explained by obesity incidence and poorer cognitive performance.
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Affiliation(s)
- Zhaolong Adrian Li
- Department of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, MO 63130, USA
- Department of Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, MO 63130, USA
| | - Yuqi Cai
- Department of Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, MO 63130, USA
| | - Rita L. Taylor
- Department of Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, MO 63130, USA
| | - Sarah A. Eisenstein
- Department of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, MO 63130, USA
- Mallinckrodt Institute of Radiology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA
| | - Deanna M. Barch
- Department of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, MO 63130, USA
- Department of Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, MO 63130, USA
- Mallinckrodt Institute of Radiology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA
| | - Scott Marek
- Mallinckrodt Institute of Radiology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA
| | - Tamara Hershey
- Department of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, MO 63130, USA
- Department of Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, MO 63130, USA
- Mallinckrodt Institute of Radiology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA
- Department of Neurology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA
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11
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Rosen CB, Altieri MS. Comment on: How much narcotics are really needed after bariatric surgery: results of a prospective study. Surg Obes Relat Dis 2023; 19:546-547. [PMID: 36792451 DOI: 10.1016/j.soard.2022.12.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Accepted: 12/27/2022] [Indexed: 01/03/2023]
Affiliation(s)
- Claire B Rosen
- Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Maria S Altieri
- Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania
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12
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Sun L, Aarnio R, Herre EA, Kärnä S, Palani S, Virtanen H, Liljenbäck H, Virta J, Honkaniemi A, Oikonen V, Han C, Laurila S, Bucci M, Helin S, Yatkin E, Nummenmaa L, Nuutila P, Tang J, Roivainen A. [ 11C]carfentanil PET imaging for studying the peripheral opioid system in vivo: effect of photoperiod on mu-opioid receptor availability in brown adipose tissue. Eur J Nucl Med Mol Imaging 2023; 50:266-274. [PMID: 36166079 PMCID: PMC9816189 DOI: 10.1007/s00259-022-05969-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 09/15/2022] [Indexed: 01/11/2023]
Abstract
PURPOSE Photoperiod determines the metabolic activity of brown adipose tissue (BAT) and affects the food intake and body mass of mammals. Sympathetic innervation of the BAT controls thermogenesis and facilitates physiological adaption to seasonal changes, but the exact mechanism remains elusive. Previous studies have shown that central opioid signaling regulates BAT thermogenesis, and that the expression of the brain mu-opioid receptor (MOR) varies seasonally. Therefore, it is important to know whether MOR expression in BAT shows seasonal variation. METHODS We determined the effect of photoperiod on BAT MOR availability using [11C]carfentanil positron emission tomography (PET). Adult rats (n = 9) were repeatedly imaged under various photoperiods in order to simulate seasonal changes. RESULTS Long photoperiod was associated with low MOR expression in BAT (β = - 0.04, 95% confidence interval: - 0.07, - 0.01), but not in muscles. We confirmed the expression of MOR in BAT and muscle using immunofluorescence staining. CONCLUSION Photoperiod affects MOR availability in BAT. Sympathetic innervation of BAT may influence thermogenesis via the peripheral MOR system. The present study supports the utility of [11C]carfentanil PET to study the peripheral MOR system.
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Affiliation(s)
- Lihua Sun
- Department of Nuclear Medicine, Huashan Hospital, Fudan University, Shanghai, China.
- Turku PET Centre, University of Turku and Turku University Hospital, 20520, Turku, Finland.
| | - Richard Aarnio
- Turku PET Centre, University of Turku and Turku University Hospital, 20520, Turku, Finland
| | - Erika Atencio Herre
- Turku PET Centre, University of Turku and Turku University Hospital, 20520, Turku, Finland
| | - Salli Kärnä
- Turku PET Centre, University of Turku and Turku University Hospital, 20520, Turku, Finland
| | - Senthil Palani
- Turku PET Centre, University of Turku and Turku University Hospital, 20520, Turku, Finland
| | - Helena Virtanen
- Turku PET Centre, University of Turku and Turku University Hospital, 20520, Turku, Finland
| | - Heidi Liljenbäck
- Turku PET Centre, University of Turku and Turku University Hospital, 20520, Turku, Finland
- Turku Center for Disease Modeling, University of Turku, 20520, Turku, Finland
| | - Jenni Virta
- Turku PET Centre, University of Turku and Turku University Hospital, 20520, Turku, Finland
| | - Aake Honkaniemi
- Turku PET Centre, University of Turku and Turku University Hospital, 20520, Turku, Finland
| | - Vesa Oikonen
- Turku PET Centre, University of Turku and Turku University Hospital, 20520, Turku, Finland
| | - Chunlei Han
- Turku PET Centre, University of Turku and Turku University Hospital, 20520, Turku, Finland
| | - Sanna Laurila
- Turku PET Centre, University of Turku and Turku University Hospital, 20520, Turku, Finland
- Heart Center, Turku University Hospital, 20520, Turku, Finland
| | - Marco Bucci
- Turku PET Centre, University of Turku and Turku University Hospital, 20520, Turku, Finland
- Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, 17177, Stockholm, Sweden
- Theme Inflammation and Aging, Karolinska University Hospital, 14186, Stockholm, Sweden
- Turku PET Centre, Åbo Akademi University, Turku, Finland
| | - Semi Helin
- Turku PET Centre, University of Turku and Turku University Hospital, 20520, Turku, Finland
| | - Emrah Yatkin
- Central Animal Laboratory, University of Turku, 20520, Turku, Finland
| | - Lauri Nummenmaa
- Turku PET Centre, University of Turku and Turku University Hospital, 20520, Turku, Finland
- Department of Psychology, University of Turku, 20520, Turku, Finland
| | - Pirjo Nuutila
- Turku PET Centre, University of Turku and Turku University Hospital, 20520, Turku, Finland
- Department of Endocrinology, Turku University Hospital, 20520, Turku, Finland
- InFLAMES Research Flagship Center, University of Turku, 20520, Turku, Finland
| | - Jing Tang
- Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, 00014, Helsinki, Finland
| | - Anne Roivainen
- Turku PET Centre, University of Turku and Turku University Hospital, 20520, Turku, Finland
- Turku Center for Disease Modeling, University of Turku, 20520, Turku, Finland
- InFLAMES Research Flagship Center, University of Turku, 20520, Turku, Finland
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13
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Pak K, Seok JW, Lee MJ, Kim K, Kim IJ. Dopamine receptor and dopamine transporter in obesity: A meta-analysis. Synapse 2023; 77:e22254. [PMID: 36099576 DOI: 10.1002/syn.22254] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 08/09/2022] [Accepted: 09/08/2022] [Indexed: 01/29/2023]
Abstract
The brain plays a major role in controlling the desire to eat. This meta-analysis aimed to assess the association between dopamine receptor (DR) availability and dopamine transporter (DAT) availability, measured using positron emission tomography, and obesity. We performed a systematic search of MEDLINE (from inception to November 2020) and EMBASE (from inception to November 2020) for articles published in English using the keywords "dopamine receptor," "dopamine transporter," "obesity," and "neuroimaging." Body mass index (BMI) and the corresponding binding potential (BPND ) were extracted from figures in each study using Engauge Digitizer, version 12.1, and plotted for radiopharmaceuticals and regions of interest (ROIs). Five studies involving 119 subjects with DR and five studies including 421 subjects with DAT were eligible for inclusion in this study. In overweight or obese subjects with BMI of 25 kg/m2 or higher, DR availability from 11 C-Racloprie was negatively associated with BMI. However, DR availability from 11 C-PHNO was positively associated with BMI. DAT ratio was calculated after dividing DAT availabilities of overweight/obese BMI with mean DAT availabilities of normal BMI. The association between DAT ratio and BMI was not significant regardless of radiopharmaceuticals. In conclusion, dopamine plays a main role in the reward system with regard to obesity. Overweight and obese subjects had negative association between DR availability from 11 C-Raclopride and BMI. However, the association of DR availability with BMI was dependent on radiopharmaceuticals. DAT availability did not show the significant relationship with BMI regardless of radiopharmaceuticals.
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Affiliation(s)
- Kyoungjune Pak
- Department of Nuclear Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
| | - Ju Won Seok
- Department of Nuclear Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea
| | - Myung Jun Lee
- Department of Neurology and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
| | - Keunyoung Kim
- Department of Nuclear Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
| | - In Joo Kim
- Department of Nuclear Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
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14
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Pekkarinen L, Kantonen T, Rebelos E, Latva-Rasku A, Dadson P, Karjalainen T, Bucci M, Kalliokoski K, Laitinen K, Houttu N, Kirjavainen AK, Rajander J, Rönnemaa T, Nummenmaa L, Nuutila P. Obesity risk is associated with brain glucose uptake and insulin resistance. Eur J Endocrinol 2022; 187:917-928. [PMID: 36288097 PMCID: PMC9782452 DOI: 10.1530/eje-22-0509] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 10/26/2022] [Indexed: 01/09/2023]
Abstract
OBJECTIVE To investigate whether alterations in brain glucose uptake (BGU), insulin action in the brain-liver axis and whole-body insulin sensitivity occur in young adults in pre-obese state. METHODS Healthy males with either high risk (HR; n = 19) or low risk (LR; n = 22) for developing obesity were studied with [18F]fluoro-d-glucose ([18F]FDG)-positron emission tomography during hyperinsulinemic-euglycemic clamp. Obesity risk was assessed according to BMI, physical activity and parental overweight/obesity and type 2 diabetes. Brain, skeletal muscle, brown adipose tissue (BAT), visceral adipose tissue (VAT) and abdominal and femoral s.c. adipose tissue (SAT) glucose uptake (GU) rates were measured. Endogenous glucose production (EGP) was calculated by subtracting the exogenous glucose infusion rate from the rate of disappearance of [18F]FDG. BGU was analyzed using statistical parametric mapping, and peripheral tissue activity was determined using Carimas Software imaging processing platform. RESULTS BGU was higher in the HR vs LR group and correlated inversely with whole-body insulin sensitivity (M value) in the HR group but not in the LR group. Insulin-suppressed EGP did not differ between the groups but correlated positively with BGU in the whole population, and the correlation was driven by the HR group. Skeletal muscle, BAT, VAT, abdominal and femoral SAT GU were lower in the HR group as compared to the LR group. Muscle GU correlated negatively with BGU in the HR group but not in the LR group. CONCLUSION Increased BGU, alterations in insulin action in the brain-liver axis and decreased whole-body insulin sensitivity occur early in pre-obese state.
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Affiliation(s)
- Laura Pekkarinen
- Turku PET Centre, University of Turku, Turku, Finland
- Department of Endocrinology, Turku University Hospital, Turku, Finland
| | - Tatu Kantonen
- Turku PET Centre, University of Turku, Turku, Finland
- Clinical Neurosciences, Turku University Hospital, Turku, Finland
| | - Eleni Rebelos
- Turku PET Centre, University of Turku, Turku, Finland
| | | | - Prince Dadson
- Turku PET Centre, University of Turku, Turku, Finland
| | | | - Marco Bucci
- Turku PET Centre, University of Turku, Turku, Finland
- Turku PET Centre, Åbo Akademi University, Turku, Finland
| | | | - Kirsi Laitinen
- Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland
| | - Noora Houttu
- Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland
| | | | - Johan Rajander
- Turku PET Centre, Åbo Akademi University, Turku, Finland
| | - Tapani Rönnemaa
- Department of Endocrinology, Turku University Hospital, Turku, Finland
- Department of Medicine, University of Turku, Turku, Finland
| | - Lauri Nummenmaa
- Turku PET Centre, University of Turku, Turku, Finland
- Department of Psychology, University of Turku, Turku, Finland
| | - Pirjo Nuutila
- Turku PET Centre, University of Turku, Turku, Finland
- Department of Endocrinology, Turku University Hospital, Turku, Finland
- Correspondence should be addressed to P Nuutila;
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15
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How Much Narcotics Are Really Needed After Bariatric Surgery: Results of a Prospective Study. Surg Obes Relat Dis 2022; 19:541-546. [DOI: 10.1016/j.soard.2022.11.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 10/01/2022] [Accepted: 11/13/2022] [Indexed: 11/21/2022]
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Morales I. Brain regulation of hunger and motivation: The case for integrating homeostatic and hedonic concepts and its implications for obesity and addiction. Appetite 2022; 177:106146. [PMID: 35753443 DOI: 10.1016/j.appet.2022.106146] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 06/16/2022] [Accepted: 06/21/2022] [Indexed: 11/19/2022]
Abstract
Obesity and other eating disorders are marked by dysregulations to brain metabolic, hedonic, motivational, and sensory systems that control food intake. Classic approaches in hunger research have distinguished between hedonic and homeostatic processes, and have mostly treated these systems as independent. Hindbrain structures and a complex network of interconnected hypothalamic nuclei control metabolic processes, energy expenditure, and food intake while mesocorticolimbic structures are though to control hedonic and motivational processes associated with food reward. However, it is becoming increasingly clear that hedonic and homeostatic brain systems do not function in isolation, but rather interact as part of a larger network that regulates food intake. Incentive theories of motivation provide a useful route to explore these interactions. Adapting incentive theories of motivation can enable researchers to better how motivational systems dysfunction during disease. Obesity and addiction are associated with profound alterations to both hedonic and homeostatic brain systems that result in maladaptive patterns of consumption. A subset of individuals with obesity may experience pathological cravings for food due to incentive sensitization of brain systems that generate excessive 'wanting' to eat. Further progress in understanding how the brain regulates hunger and appetite may depend on merging traditional hedonic and homeostatic concepts of food reward and motivation.
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Affiliation(s)
- Ileana Morales
- Department of Psychology, University of Michigan, 530 Church Street, Ann Arbor, MI, 48109-1043, USA.
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17
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Gerhart JG, Carreño FO, Ford JL, Edginton A, Perrin EM, Watt KM, Muller WJ, Atz AM, Al‐Uzri A, Delmore P, Gonzalez D, Benjamin DK, Hornik C, Zimmerman K, Kennel P, Beci R, Dang Hornik C, Kearns GL, Laughon M, Paul IM, Sullivan J, Wade K, Delmore P, Taylor‐Zapata P, Lee J, Anand R, Sharma G, Simone G, Kaneshige K, Taylor L, Al‐Uzri A, Hornik C, Sokol G, Speicher D, Sullivan J, Mourani P, Mendley S, Meyer M, Atkins R, Flynn J, Vaughns J, Sherwin C, Delmore P, Goldstein S, Rathore M, Melloni C, Muller W, Delmore P, Tremoulet A, James L, Mendley S, Blackford M, Atz A, Adu‐Darko M, Mourani P, Watt K, Hornik C, Al‐Uzri A, Sullivan J, Laughon M, Brian Smith P, Watt K, Cheifetz I, Atz A, Bhatt‐Mehta V, Fernandez A, Lowry J, Best Pharmaceuticals for Children Act–Pediatric Trials Network Steering Committee. Use of
physiologically‐based
pharmacokinetic modeling to inform dosing of the opioid analgesics fentanyl and methadone in children with obesity. CPT Pharmacometrics Syst Pharmacol 2022; 11:778-791. [PMID: 35491971 PMCID: PMC9197535 DOI: 10.1002/psp4.12793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 03/18/2022] [Accepted: 03/22/2022] [Indexed: 11/12/2022] Open
Abstract
Obesity is an increasingly alarming public health threat, with nearly 20% of children classified as obese in the United States today. Children with obesity are commonly prescribed the opioids fentanyl and methadone, and accurate dosing is critical to reducing the risk of serious adverse events associated with overexposure. However, pharmacokinetic studies in children with obesity are challenging to conduct, so there is limited information to guide fentanyl and methadone dosing in these children. To address this clinical knowledge gap, physiologically‐based pharmacokinetic models of fentanyl and methadone were developed in adults and scaled to children with and without obesity to explore the interplay of obesity, age, and pharmacogenomics. These models included key obesity‐induced changes in physiology and pharmacogenomic effects. Model predictions captured observed concentrations in children with obesity well, with an overall average fold error of 0.72 and 1.08 for fentanyl and methadone, respectively. Model simulations support a reduced fentanyl dose (1 vs. 2 μg/kg/h) starting at an earlier age (6 years) in virtual children with obesity, highlighting the importance of considering both age and obesity status when selecting an infusion rate most likely to achieve steady‐state concentrations within the target range. Methadone dosing simulations highlight the importance of considering genotype in addition to obesity status when possible, as cytochrome P450 (CYP)2B6*6/*6 virtual children with obesity required half the dose to match the exposure of wildtype children without obesity. This physiologically‐based pharmacokinetic modeling approach can be applied to explore dosing of other critical drugs in children with obesity.
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Affiliation(s)
- Jacqueline G. Gerhart
- Division of Pharmacotherapy and Experimental Therapeutics, The University of North Carolina Eshelman School of Pharmacy The University of North Carolina at Chapel Hill Chapel Hill North Carolina USA
| | - Fernando O. Carreño
- Division of Pharmacotherapy and Experimental Therapeutics, The University of North Carolina Eshelman School of Pharmacy The University of North Carolina at Chapel Hill Chapel Hill North Carolina USA
| | - Jennifer L. Ford
- Division of Pharmacotherapy and Experimental Therapeutics, The University of North Carolina Eshelman School of Pharmacy The University of North Carolina at Chapel Hill Chapel Hill North Carolina USA
| | | | - Eliana M. Perrin
- Department of Pediatrics, School of Medicine and School of Nursing Johns Hopkins University Baltimore Maryland USA
| | - Kevin M. Watt
- Division of Pediatric Clinical Pharmacology, School of Medicine University of Utah Salt Lake City Utah USA
| | - William J. Muller
- Ann and Robert H. Lurie Children's Hospital of Chicago Chicago Illinois USA
| | - Andrew M. Atz
- Medical University of South Carolina Children's Hospital Charleston South Carolina USA
| | - Amira Al‐Uzri
- Oregon Health and Science University Portland Oregon USA
| | | | - Daniel Gonzalez
- Division of Pharmacotherapy and Experimental Therapeutics, The University of North Carolina Eshelman School of Pharmacy The University of North Carolina at Chapel Hill Chapel Hill North Carolina USA
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18
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Atlas of type 2 dopamine receptors in the human brain: Age and sex dependent variability in a large PET cohort. Neuroimage 2022; 255:119149. [PMID: 35367652 DOI: 10.1016/j.neuroimage.2022.119149] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 03/22/2022] [Accepted: 03/24/2022] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND The dopamine system contributes to a multitude of functions ranging from reward and motivation to learning and movement control, making it a key component in goal-directed behavior. Altered dopaminergic function is observed in neurological and psychiatric conditions. Numerous factors have been proposed to influence dopamine function, but due to small sample sizes and heterogeneous data analysis methods in previous studies their specific and joint contributions remain unresolved. METHODS In this cross-sectional register-based study we investigated how age, sex, body mass index (BMI), as well as cerebral hemisphere and regional volume influence striatal type 2 dopamine receptor (D2R) availability in the human brain. We analyzed a large historical dataset (n=156, 120 males and 36 females) of [11C]raclopride PET scans performed between 2004 and 2018. RESULTS Striatal D2R availability decreased through age for both sexes (2-5 % in striatal ROIs per 10 years) and was higher in females versus males throughout age (7-8% in putamen). BMI and striatal D2R availability were weakly associated. There was no consistent lateralization of striatal D2R. The observed effects were independent of regional volumes. These results were validated using two different spatial normalization methods, and the age and sex effects also replicated in an independent sample (n=135). CONCLUSIONS D2R availability is dependent on age and sex, which may contribute to the vulnerability of neurological and psychiatric conditions involving altering D2R expression.
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Tatarchuk T, Todurov I, Anagnostis P, Tutchenko T, Pedachenko N, Glamazda M, Koseii N, Regeda S. The Effect of Gastric Sleeve Resection on Menstrual Pattern and Ovulation in Premenopausal Women with Classes III-IV Obesity. Obes Surg 2021; 32:599-606. [PMID: 34817794 DOI: 10.1007/s11695-021-05820-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 11/14/2021] [Accepted: 11/17/2021] [Indexed: 11/29/2022]
Abstract
PURPOSE Bariatric surgery is very efficacious in treating severe obesity. However, its effect on menstruation and ovulation is currently unknown. The purpose of this study was to assess the effect of gastric sleeve resection (GSR) on menstrual pattern in women with stages III-IV obesity and ovulatory dysfunction compared with conventional management. METHODS This was a prospective, multicentre, non-randomized trial, in premenopausal women, who fulfilled the criteria for gastric sleeve resection (GSR). Both women with and without polycystic ovary syndrome (PCOS) were evaluated at 3, 6, 9, 12 and 15 months post-surgery. RESULTS Menstrual cycle irregularities were identified in 122 severely obese women (60 with PCOS; 62 without PCOS). The % total weight loss was greater with GSR than with conventional management (33.4% vs. 3.6% in PCOS; 24.8% vs. 3.6% in non-PCOS, respectively). Intermenstrual interval was shortened towards normal length (≤ 35 days) both in PCOS and non-PCOS GSR groups, by the 6th and 12th post-surgical month, respectively. Furthermore, ovulation at 6 months was achieved in 63.6% of PCOS and 45% of non-PCOS subjects post-GSR, which was higher than in controls (11.1% and 13.6%, respectively; p < 0.05). This percentage rose to 75.7% and 81.8% at 12 and 15 months in PCOS, respectively, but not in the non-PCOS group (55% and 52.5%, respectively; p < 0.05). CONCLUSIONS Weight reduction after GSR improved menstrual irregularity towards normality in women with severe obesity. Ovulation dysfunction was also resumed in more than half of these patients at 6-15 months. These effects were more evident in women with PCOS.
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Affiliation(s)
- Tetiana Tatarchuk
- Institute of Pediatrics, Obstetrics and Gynecology of the Academy of Medical Sciences of Ukraine, 8 Platon Mayboroda St, Kyiv, 04050, Ukraine
| | - Ivan Todurov
- Center for Innovative Medical Technologies, Academy of Sciences of Ukraine, 22 Voznesenskiy Uzviz St, Kyiv, 04053, Ukraine
| | - Panagiotis Anagnostis
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
| | - Tetiana Tutchenko
- Institute of Pediatrics, Obstetrics and Gynecology of the Academy of Medical Sciences of Ukraine, 8 Platon Mayboroda St, Kyiv, 04050, Ukraine
| | - Natalia Pedachenko
- Department of Obstetrics, Gynecology and Perinatology, P.L. Shupik National Healthcare University of Ukraine, Kyiv, Ukraine
| | - Marina Glamazda
- Institute of Pediatrics, Obstetrics and Gynecology of the Academy of Medical Sciences of Ukraine, 8 Platon Mayboroda St, Kyiv, 04050, Ukraine
| | - Natalia Koseii
- Institute of Pediatrics, Obstetrics and Gynecology of the Academy of Medical Sciences of Ukraine, 8 Platon Mayboroda St, Kyiv, 04050, Ukraine
| | - Svetlana Regeda
- Institute of Pediatrics, Obstetrics and Gynecology of the Academy of Medical Sciences of Ukraine, 8 Platon Mayboroda St, Kyiv, 04050, Ukraine
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20
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Obesity risk is associated with altered cerebral glucose metabolism and decreased μ-opioid and CB 1 receptor availability. Int J Obes (Lond) 2021; 46:400-407. [PMID: 34728775 PMCID: PMC8794779 DOI: 10.1038/s41366-021-00996-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 07/06/2021] [Accepted: 10/12/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Obesity is a pressing public health concern worldwide. Novel pharmacological means are urgently needed to combat the increase of obesity and accompanying type 2 diabetes (T2D). Although fully established obesity is associated with neuromolecular alterations and insulin resistance in the brain, potential obesity-promoting mechanisms in the central nervous system have remained elusive. In this triple-tracer positron emission tomography study, we investigated whether brain insulin signaling, μ-opioid receptors (MORs) and cannabinoid CB1 receptors (CB1Rs) are associated with risk for developing obesity. METHODS Subjects were 41 young non-obese males with variable obesity risk profiles. Obesity risk was assessed by subjects' physical exercise habits, body mass index and familial risk factors, including parental obesity and T2D. Brain glucose uptake was quantified with [18F]FDG during hyperinsulinemic euglycemic clamp, MORs were quantified with [11C]carfentanil and CB1Rs with [18F]FMPEP-d2. RESULTS Subjects with higher obesity risk had globally increased insulin-stimulated brain glucose uptake (19 high-risk subjects versus 19 low-risk subjects), and familial obesity risk factors were associated with increased brain glucose uptake (38 subjects) but decreased availability of MORs (41 subjects) and CB1Rs (36 subjects). CONCLUSIONS These results suggest that the hereditary mechanisms promoting obesity may be partly mediated via insulin, opioid and endocannabinoid messaging systems in the brain.
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21
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Bini J, Norcross M, Cheung M, Duffy A. The Role of Positron Emission Tomography in Bariatric Surgery Research: a Review. Obes Surg 2021; 31:4592-4606. [PMID: 34304378 DOI: 10.1007/s11695-021-05576-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 06/24/2021] [Accepted: 06/30/2021] [Indexed: 12/15/2022]
Abstract
Bariatric surgery, initially understood as restricting or bypassing the amount of food that reaches the stomach to reduce food intake and/or increase malabsorption of food to promote weight loss, is now recognized to also affect incretin signaling in the gut and promote improvements in system-wide metabolism. Positron emission tomography (PET) is an imaging technique whereby patients are injected with picomolar concentrations of radioactive molecules, below the threshold of having physiological effects, to measure spatial distributions of blood flow, metabolism, receptor, and enzyme pharmacology. Recent advances in both whole-body PET imaging and radioligand development will allow for novel research that may help clarify the roles of peripheral and central receptor/enzyme systems in treating obesity with bariatric surgery.
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Affiliation(s)
- Jason Bini
- Yale PET Center, Department of Radiology and Biomedical Imaging, Yale University School of Medicine, 801 Howard Avenue, PO Box 208048, New Haven, CT, USA.
| | | | - Maija Cheung
- Department of Surgery, Yale University School of Medicine, New Haven, CT, USA
| | - Andrew Duffy
- Department of Surgery, Yale University School of Medicine, New Haven, CT, USA
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Karlsson HK, Tuominen L, Helin S, Salminen P, Nuutila P, Nummenmaa L. Preoperative brain μ-opioid receptor availability predicts weight development following bariatric surgery in women. JCI Insight 2021; 6:147820. [PMID: 33848266 PMCID: PMC8262287 DOI: 10.1172/jci.insight.147820] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Accepted: 04/07/2021] [Indexed: 01/15/2023] Open
Abstract
Bariatric surgery is the most effective method for weight loss in morbid obesity. There is significant individual variability in the weight loss outcomes, yet factors leading to postoperative weight loss or weight regain remain elusive. Alterations in the μ-opioid receptor (MOR) and dopamine D2 receptor (D2R) systems are associated with obesity and appetite control, and the magnitude of initial brain receptor system perturbation may predict long-term surgical weight loss outcomes. We tested this hypothesis by studying 19 morbidly obese women (mean BMI 40) scheduled to undergo bariatric surgery. We measured their preoperative MOR and D2R availabilities using positron emission tomography with [11C]carfentanil and [11C]raclopride, respectively, and then assessed their weight development association with regional MOR and D2R availabilities at 24-month follow-up. MOR availability in the amygdala consistently predicted weight development throughout the follow-up period, but no associations were found for D2R. This is the first study to our knowledge to demonstrate that neuroreceptor markers prior to bariatric surgery are associated with postoperative weight development. Postoperative weight regain may derive from dysfunction in the opioid system, and weight loss outcomes after bariatric surgery may be partially predicted based on preoperative brain receptor availability, opening up new potential for treatment possibilities.
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Affiliation(s)
- Henry K Karlsson
- Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland
| | - Lauri Tuominen
- Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland.,Institute of Mental Health Research, University of Ottawa, Ottawa, Ontario, Canada
| | - Semi Helin
- Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland
| | - Paulina Salminen
- Division of Digestive Surgery and Urology, Turku University Hospital, Turku, Finland.,Department of Surgery, University of Turku, Turku, Finland
| | - Pirjo Nuutila
- Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland.,Department of Endocrinology, Turku University Hospital, Turku, Finland
| | - Lauri Nummenmaa
- Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland.,Department of Psychology, University of Turku, Turku, Finland
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24
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Ashok AH, Myers J, Frost G, Turton S, Gunn RN, Passchier J, Colasanti A, Marques TR, Nutt D, Lingford-Hughes A, Howes OD, Rabiner EA. Acute acetate administration increases endogenous opioid levels in the human brain: A [ 11C]carfentanil molecular imaging study. J Psychopharmacol 2021; 35:606-610. [PMID: 33406950 PMCID: PMC8155733 DOI: 10.1177/0269881120965912] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
INTRODUCTION A recent study has shown that acetate administration leads to a fourfold increase in the transcription of proopiomelanocortin (POMC) mRNA in the hypothalamus. POMC is cleaved to peptides, including β-endorphin, an endogenous opioid (EO) agonist that binds preferentially to the µ-opioid receptor (MOR). We hypothesised that an acetate challenge would increase the levels of EO in the human brain. We have previously demonstrated that increased EO release in the human brain can be detected using positron emission tomography (PET) with the selective MOR radioligand [11C]carfentanil. We used this approach to evaluate the effects of an acute acetate challenge on EO levels in the brain of healthy human volunteers. METHODS Seven volunteers each completed a baseline [11C]carfentanil PET scan followed by an administration of sodium acetate before a second [11C]carfentanil PET scan. Dynamic PET data were acquired over 90 minutes, and corrected for attenuation, scatter and subject motion. Regional [11C] carfentanil BPND values were then calculated using the simplified reference tissue model (with the occipital grey matter as the reference region). Change in regional EO concentration was evaluated as the change in [11C]carfentanil BPND following acetate administration. RESULTS Following sodium acetate administration, 2.5-6.5% reductions in [11C]carfentanil regional BPND were seen, with statistical significance reached in the cerebellum, temporal lobe, orbitofrontal cortex, striatum and thalamus. CONCLUSIONS We have demonstrated that an acute acetate challenge has the potential to increase EO release in the human brain, providing a plausible mechanism of the central effects of acetate on appetite in humans.
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Affiliation(s)
- Abhishekh H Ashok
- Psychiatric Imaging Group, MRC London Institute of Medical Sciences (LMS), Imperial College London, London, UK.,Psychiatric Imaging Group, Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London, UK.,Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.,Department of Radiology, University of Cambridge, Cambridge, UK.,Department of Radiology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | | | | | - Samuel Turton
- Imperial College London, UK.,Institute of Psychiatry, Psychology and Neurosciences, King's College London, London, UK
| | - Roger N Gunn
- Imperial College London, UK.,Invicro, London, UK
| | | | - Alessandro Colasanti
- Department of Neuroscience, Brighton and Sussex Medical School, University of Sussex, Brighton, UK
| | - Tiago Reis Marques
- Psychiatric Imaging Group, MRC London Institute of Medical Sciences (LMS), Imperial College London, London, UK.,Psychiatric Imaging Group, Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London, UK.,Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | | | | | - Oliver D Howes
- Psychiatric Imaging Group, MRC London Institute of Medical Sciences (LMS), Imperial College London, London, UK.,Psychiatric Imaging Group, Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London, UK.,Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Eugenii A Rabiner
- Institute of Psychiatry, Psychology and Neurosciences, King's College London, London, UK.,Invicro, London, UK
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25
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Mesolimbic opioid-dopamine interaction is disrupted in obesity but recovered by weight loss following bariatric surgery. Transl Psychiatry 2021; 11:259. [PMID: 33934103 PMCID: PMC8088437 DOI: 10.1038/s41398-021-01370-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Revised: 03/18/2021] [Accepted: 04/06/2021] [Indexed: 12/02/2022] Open
Abstract
Obesity is a growing burden to health and the economy worldwide. Obesity is associated with central µ-opioid receptor (MOR) downregulation and disruption of the interaction between MOR and dopamine D2 receptor (D2R) system in the ventral striatum. Weight loss recovers MOR function, but it remains unknown whether it also recovers aberrant opioid-dopamine interaction. Here we addressed this issue by studying 20 healthy non-obese and 25 morbidly obese women (mean BMI 41) eligible for bariatric surgery. Brain MOR and D2R availability were measured using positron emission tomography (PET) with [11C]carfentanil and [11C]raclopride, respectively. Either Roux-en-Y gastric bypass or sleeve gastrectomy was performed on obese subjects according to standard clinical treatment. 21 obese subjects participated in the postoperative PET scanning six months after bariatric surgery. In the control subjects, MOR and D2R availabilities were associated in the ventral striatum (r = .62) and dorsal caudate (r = .61). Preoperatively, the obese subjects had disrupted association in the ventral striatum (r = .12) but the unaltered association in dorsal caudate (r = .43). The association between MOR and D2R availabilities in the ventral striatum was recovered (r = .62) among obese subjects following the surgery-induced weight loss. Bariatric surgery and concomitant weight loss recover the interaction between MOR and D2R in the ventral striatum in the morbidly obese. Consequently, the dysfunctional opioid-dopamine interaction in the ventral striatum is likely associated with an obese phenotype and may mediate excessive energy uptake. Striatal opioid-dopamine interaction provides a feasible target for pharmacological and behavioral interventions for treating obesity.
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26
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Manninen S, Karjalainen T, Tuominen LJ, Hietala J, Kaasinen V, Joutsa J, Rinne J, Nummenmaa L. Cerebral grey matter density is associated with neuroreceptor and neurotransporter availability: A combined PET and MRI study. Neuroimage 2021; 235:117968. [PMID: 33785434 DOI: 10.1016/j.neuroimage.2021.117968] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 02/12/2021] [Accepted: 03/05/2021] [Indexed: 12/21/2022] Open
Abstract
Positron emission tomography (PET) can be used for in vivo measurement of specific neuroreceptors and transporters using radioligands, while voxel-based morphometric analysis of magnetic resonance images allows automated estimation of local grey matter densities. However, it is not known how regional neuroreceptor or transporter densities are reflected in grey matter densities. Here, we analyzed brain scans retrospectively from 328 subjects and compared grey matter density estimates with neuroreceptor and transporter availabilities. µ-opioid receptors (MORs) were measured with [11C]carfentanil (162 scans), dopamine D2 receptors with [11C]raclopride (92 scans) and serotonin transporters (SERT) with [11C]MADAM (74 scans). The PET data were modelled with simplified reference tissue model. Voxel-wise correlations between binding potential and grey matter density images were computed. Regional binding of all the used radiotracers was associated with grey matter density in region and ligand-specific manner independently of subjects' age or sex. These data show that grey matter density and MOR and D2R neuroreceptor / SERT availability are correlated, with effect sizes (r2) ranging from 0.04 to 0.69. This suggests that future studies comparing PET outcome measure different groups (such as patients and controls) should also analyze interactive effects of grey matter density and PET outcome measures.
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Affiliation(s)
- Sandra Manninen
- Turku Pet Centre and Turku University Hospital, Turku, Finland.
| | | | - Lauri J Tuominen
- Turku Pet Centre and Turku University Hospital, Turku, Finland; University of Ottawa, Institute of Mental Health Research, Ottawa, Ontario, Canada
| | - Jarmo Hietala
- Department of Psychiatry, Turku University Hospital, Turku, Finland
| | - Valtteri Kaasinen
- Clinical Neurosciences, University of Turku, Turku, Finland; Neurocenter, Turku University Hospital, Turku, Finland
| | - Juho Joutsa
- Clinical Neurosciences, University of Turku, Turku, Finland
| | - Juha Rinne
- Turku Pet Centre and Turku University Hospital, Turku, Finland
| | - Lauri Nummenmaa
- Turku Pet Centre and Turku University Hospital, Turku, Finland; Department of Psychology, University of Turku, Finland
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27
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Adil SM, Charalambous LT, Spears CA, Kiyani M, Hodges SE, Yang Z, Lee HJ, Rahimpour S, Parente B, Greene KA, McClellan M, Lad SP. Impact of Spinal Cord Stimulation on Opioid Dose Reduction: A Nationwide Analysis. Neurosurgery 2021; 88:193-201. [PMID: 32866229 DOI: 10.1093/neuros/nyaa353] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Accepted: 06/19/2020] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND Opioid misuse in the USA is an epidemic. Utilization of neuromodulation for refractory chronic pain may reduce opioid-related morbidity and mortality, and associated economic costs. OBJECTIVE To assess the impact of spinal cord stimulation (SCS) on opioid dose reduction. METHODS The IBM MarketScan® database was retrospectively queried for all US patients with a chronic pain diagnosis undergoing SCS between 2010 and 2015. Opioid usage before and after the procedure was quantified as morphine milligram equivalents (MME). RESULTS A total of 8497 adult patients undergoing SCS were included. Within 1 yr of the procedure, 60.4% had some reduction in their opioid use, 34.2% moved to a clinically important lower dosage group, and 17.0% weaned off opioids entirely. The proportion of patients who completely weaned off opioids increased with decreasing preprocedure dose, ranging from 5.1% in the >90 MME group to 34.2% in the ≤20 MME group. The following variables were associated with reduced odds of weaning off opioids post procedure: long-term opioid use (odds ratio [OR]: 0.26; 95% CI: 0.21-0.30; P < .001), use of other pain medications (OR: 0.75; 95% CI: 0.65-0.87; P < .001), and obesity (OR: 0.75; 95% CI: 0.60-0.94; P = .01). CONCLUSION Patients undergoing SCS were able to reduce opioid usage. Given the potential to reduce the risks of long-term opioid therapy, this study lays the groundwork for efforts that may ultimately push stakeholders to reduce payment and policy barriers to SCS as part of an evidence-based, patient-centered approach to nonopioid solutions for chronic pain.
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Affiliation(s)
- Syed M Adil
- Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina
| | - Lefko T Charalambous
- Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina
| | - Charis A Spears
- Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina
| | - Musa Kiyani
- Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina
| | - Sarah E Hodges
- Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina
| | - Zidanyue Yang
- Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina
| | - Hui-Jie Lee
- Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina
| | - Shervin Rahimpour
- Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina
| | - Beth Parente
- Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina
| | - Kathryn A Greene
- Duke-Robert J. Margolis Center for Health Policy, Duke University, Durham, North Carolina
| | - Mark McClellan
- Duke-Robert J. Margolis Center for Health Policy, Duke University, Durham, North Carolina
| | - Shivanand P Lad
- Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina
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28
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Ribeiro G, Camacho M, Fernandes AB, Cotovio G, Torres S, Oliveira-Maia AJ. Reward-related gustatory and psychometric predictors of weight loss following bariatric surgery: a multicenter cohort study. Am J Clin Nutr 2021; 113:751-761. [PMID: 33558894 PMCID: PMC7948842 DOI: 10.1093/ajcn/nqaa349] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Accepted: 10/27/2020] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Reward sensitivity has been proposed as a potential mediator of outcomes for bariatric surgery. OBJECTIVES We aimed to determine whether gustatory and psychometric measures of reward-related feeding are predictors of bariatric-induced weight loss. METHODS A multicenter longitudinal cohort study was conducted in patients scheduled for bariatric surgery (surgical group), assessed at baseline and 2 follow-up assessments. Predictions of % weight loss from baseline (%WL) according to baseline gustatory measures, including intensity and pleasantness ratings of sweet and other tastants, and psychometric measures of reward-related feeding behavior, including hedonic hunger scores, were assessed with multivariable linear regression. Exploratory analyses were conducted to test for associations between %WL and changes in gustatory and psychophysical measures, as well as for comparisons with data from patients on the surgery waiting list (control group). RESULTS We included 212 patients, of whom 96 in the surgical group and 50 in the control group were prospectively assessed. The groups were similar at baseline and, as expected, bariatric surgery resulted in higher %WL (BTreatment-Time = 2.4; 95% CI: 2.1-2.8; P < 0.0001). While variation in gustatory measures did not differ between groups, in the surgery group baseline sweet intensity predicted %WL at the primary endpoint (11 to 18 months postoperatively; β = 0.2; B = 0.2, 95% CI: 0.02 to 0.3; P = 0.02), as did hedonic hunger scores (β = -0.2; B = -2.0, 95% CI: -3.8 to -0.3; P = 0.02). Furthermore, at this endpoint, postsurgical reduction of sweet taste intensity and acceptance of sweet foods were associated with %WL (β = -0.3; B = -3.5, 95% CI: -5.8 to -1.3; P = 0.003, and β = -0.2; B = -4.7, 95% CI: -8.5 to -0.8; P = 0.02, respectively). The use of sweet intensity as a predictor of weight change was confirmed in another bariatric cohort. CONCLUSIONS Sweet intensity ratings and hedonic hunger scores predict %WL after surgery. The variability of sweet intensity ratings is also associated with %WL, further suggesting they may reflect physiological processes that are variably modulated by bariatric surgery, influencing clinical outcomes.
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Affiliation(s)
- Gabriela Ribeiro
- Champalimaud Research & Clinical Centre, Champalimaud Centre for the Unknown, Lisboa, Portugal,Lisbon Academic Medical Centre PhD Program, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
| | - Marta Camacho
- Present address for MC: John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
| | - Ana B Fernandes
- Champalimaud Research & Clinical Centre, Champalimaud Centre for the Unknown, Lisboa, Portugal,NOVA Medical School, NMS, Universidade Nova de Lisboa, Lisboa, Portugal
| | - Gonçalo Cotovio
- Champalimaud Research & Clinical Centre, Champalimaud Centre for the Unknown, Lisboa, Portugal,NOVA Medical School, NMS, Universidade Nova de Lisboa, Lisboa, Portugal,Department of Psychiatry and Mental Health, Centro Hospitalar de Lisboa Ocidental, Lisboa, Portugal
| | - Sandra Torres
- Faculdade de Psicologia e de Ciências da Educação, Universidade do Porto, Porto, Portugal,Centro de Psicologia da Universidade do Porto, Porto, Portugal
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29
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Hu Y, Ji G, Li G, Manza P, Zhang W, Wang J, Lv G, He Y, Zhang Z, Yuan K, von Deneen KM, Chen A, Cui G, Wang H, Wiers CE, Volkow ND, Nie Y, Zhang Y, Wang GJ. Brain Connectivity, and Hormonal and Behavioral Correlates of Sustained Weight Loss in Obese Patients after Laparoscopic Sleeve Gastrectomy. Cereb Cortex 2021; 31:1284-1295. [PMID: 33037819 PMCID: PMC8179510 DOI: 10.1093/cercor/bhaa294] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 09/01/2020] [Accepted: 09/01/2020] [Indexed: 12/12/2022] Open
Abstract
The biological mediators that support cognitive-control and long-term weight-loss after laparoscopic sleeve gastrectomy (LSG) remain unclear. We measured peripheral appetitive hormones and brain functional-connectivity (FC) using magnetic-resonance-imaging with food cue-reactivity task in 25 obese participants at pre, 1 month, and 6 month after LSG, and compared with 30 normal weight controls. We also used diffusion-tensor-imaging to explore whether LSG increases brain structural-connectivity (SC) of regions involved in food cue-reactivity. LSG significantly decreased BMI, craving for high-calorie food cues, ghrelin, insulin, and leptin levels, and increased self-reported cognitive-control of eating behavior. LSG increased FC between the right dorsolateral prefrontal cortex (DLPFC) and the pregenual anterior cingulate cortex (pgACC) and increased SC between DLPFC and ACC at 1 month and 6 month after LSG. Reduction in BMI correlated negatively with increased FC of right DLPFC-pgACC at 1 month and with increased SC of DLPFC-ACC at 1 month and 6 month after LSG. Reduction in craving for high-calorie food cues correlated negatively with increased FC of DLPFC-pgACC at 6 month after LSG. Additionally, SC of DLPFC-ACC mediated the relationship between lower ghrelin levels and greater cognitive control. These findings provide evidence that LSG improved functional and structural connectivity in prefrontal regions, which contribute to enhanced cognitive-control and sustained weight-loss following surgery.
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Affiliation(s)
- Yang Hu
- Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi 710071, China
| | - Gang Ji
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi 710032, China
| | - Guanya Li
- Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi 710071, China
| | - Peter Manza
- Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA
| | - Wenchao Zhang
- Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi 710071, China
| | - Jia Wang
- Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi 710071, China
| | - Ganggang Lv
- Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi 710071, China
| | - Yang He
- Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi 710071, China
| | - Zhida Zhang
- Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi 710071, China
| | - Kai Yuan
- Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi 710071, China
| | - Karen M von Deneen
- Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi 710071, China
| | - Antao Chen
- Department of Psychology, Southwest University, Chongqing 400715, China
| | - Guangbin Cui
- Department of Radiology, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi 710038, China
| | - Huaning Wang
- Department of Psychiatry, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China
| | - Corinde E Wiers
- Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA
| | - Nora D Volkow
- Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA
| | - Yongzhan Nie
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi 710032, China
| | - Yi Zhang
- Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi 710071, China
| | - Gene-Jack Wang
- Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA
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30
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Boswell RG, Potenza MN, Grilo CM. The Neurobiology of Binge-eating Disorder Compared with Obesity: Implications for Differential Therapeutics. Clin Ther 2021; 43:50-69. [PMID: 33257092 PMCID: PMC7902428 DOI: 10.1016/j.clinthera.2020.10.014] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 10/30/2020] [Accepted: 10/30/2020] [Indexed: 12/13/2022]
Abstract
PURPOSE Emerging work indicates divergence in the neurobiologies of binge-eating disorder (BED) and obesity despite their frequent co-occurrence. This review highlights specific distinguishing aspects of BED, including elevated impulsivity and compulsivity possibly involving the mesocorticolimbic dopamine system, and discusses implications for differential therapeutics for BED. METHODS This narrative review describes epidemiologic, clinical, genetic, and preclinical differences between BED and obesity. Subsequently, this review discusses human neuroimaging work reporting differences in executive functioning, reward processing, and emotion reactivity in BED compared with obesity. Finally, on the basis of the neurobiology of BED, this review identifies existing and new therapeutic agents that may be most promising given their specific targets based on putative mechanisms of action relevant specifically to BED. FINDINGS BED is characterized by elevated impulsivity and compulsivity compared with obesity, which is reflected in divergent neurobiological characteristics and effective pharmacotherapies. Therapeutic agents that influence both reward and executive function systems may be especially effective for BED. IMPLICATIONS Greater attention to impulsivity/compulsivity-related, reward-related, and emotion reactivity-related processes may enhance conceptualization and treatment approaches for patients with BED. Consideration of these distinguishing characteristics and processes could have implications for more targeted pharmacologic treatment research and interventions.
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Affiliation(s)
- Rebecca G Boswell
- Yale School of Medicine, Department of Psychiatry, New Haven, CT, USA.
| | - Marc N Potenza
- Yale School of Medicine, Department of Psychiatry, New Haven, CT, USA; Connecticut Mental Health Center, New Haven, CT, USA; Connecticut Council on Problem Gambling, Wethersfield, CT, USA; Yale School of Medicine, Child Study Center, New Haven, CT, USA; Yale University, Department of Neuroscience, New Haven, CT, USA
| | - Carlos M Grilo
- Yale School of Medicine, Department of Psychiatry, New Haven, CT, USA; Yale University, Department of Psychology, New Haven, CT, USA
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31
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Li P, Shan H, Nie B, Liu H, Dong G, Guo Y, Du J, Gao H, Ma L, Li D, Shan B. Sleeve Gastrectomy Rescuing the Altered Functional Connectivity of Lateral but Not Medial Hypothalamus in Subjects with Obesity. Obes Surg 2020; 29:2191-2199. [PMID: 30895508 DOI: 10.1007/s11695-019-03822-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Lateral and medial hypothalamus (LH and MH) play important roles in energy balance. Changed hypothalamic function has been found in subjects with obesity. However, the effect of bariatric surgery on the function of the two sub-regions has been poorly investigated. METHODS Thirty-eight subjects with obesity and 34 age- and sex-matched normal-weight controls were included. Seventeen of the 38 subjects underwent laparoscopic sleeve gastrectomy. Functional magnetic resonance imaging data and metabolic parameters were collected to investigate functional connectivity networks of the two hypothalamic sub-regions as well as the influence of sleeve gastrectomy on the two networks in subjects with obesity. RESULTS Compared to normal-weight controls, pre-surgical subjects had increased functional connectivity (FC) in the reward region (putamen) within the LH network, and increased FC in somatosensory cortical area (insula), as well as decreased FC in the cognitive control regions (prefrontal regions) within the MH network. After the surgery, post-surgical FC of the putamen within the LH network changed towards the patterns found in the control group. Furthermore, the changes in fasting glucose before and after the surgery were associated with the changes in FC of the putamen within the LH network. CONCLUSIONS The FC within the LH and MH networks were changed in subjects with obesity. Part of these altered FC was rescued after the surgery.
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Affiliation(s)
- Panlong Li
- Department of Physics, Zhengzhou University, Zhengzhou, 450001, Henan, China.,Division of Nuclear Technology and Applications, Beijing Engineering Research Center of Radiographic Techniques and Equipment, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China.,School of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Han Shan
- Department of Radiology, Chinese People's Liberation Army General Hospital, Beijing, 100853, China
| | - Binbin Nie
- Division of Nuclear Technology and Applications, Beijing Engineering Research Center of Radiographic Techniques and Equipment, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China.,School of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Hua Liu
- Division of Nuclear Technology and Applications, Beijing Engineering Research Center of Radiographic Techniques and Equipment, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China.,School of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Guanglong Dong
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Yulin Guo
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Jin Du
- Department of Endocrinology, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Hongkai Gao
- Department of General Surgery, The General Hospital of Chinese People's Armed Police Forces, Beijing, 100039, China
| | - Lin Ma
- Department of Radiology, Chinese People's Liberation Army General Hospital, Beijing, 100853, China.
| | - Demin Li
- Department of Physics, Zhengzhou University, Zhengzhou, 450001, Henan, China.
| | - Baoci Shan
- Division of Nuclear Technology and Applications, Beijing Engineering Research Center of Radiographic Techniques and Equipment, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China. .,School of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing, 100049, China. .,CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai, China.
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Hankir MK, Al-Bas S, Rullmann M, Chakaroun R, Seyfried F, Pleger B. Homeostatic, reward and executive brain functions after gastric bypass surgery. Appetite 2020; 146:104419. [DOI: 10.1016/j.appet.2019.104419] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Revised: 07/01/2019] [Accepted: 08/23/2019] [Indexed: 12/15/2022]
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Ehlers AP, Sullivan KM, Stadeli KM, Monu JI, Chen-Meekin JY, Khandelwal S. Opioid Use Following Bariatric Surgery: Results of a Prospective Survey. Obes Surg 2019; 30:1032-1037. [PMID: 31808115 DOI: 10.1007/s11695-019-04301-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Opioid use after bariatric surgery is not clearly understood. Few guidelines exist to inform opioid-prescribing practices after bariatric surgery. OBJECTIVE To understand opioid use following bariatric surgery. SETTING University hospital. METHODS Bariatric surgery patients at a single center were prospectively surveyed at the time of their post-operative visit (January-May 2018). Patients were asked about their opioid use following surgery, whether they received education about opioid use and what they did with leftover medications. Demographic and operative details were obtained from the medical record. RESULTS Among 33 patients, the majority (n = 29, 88%) were female with a median age of 40 (20-68) and body mass index of 44.8 (33-78.5). Most patients had leftover narcotics (n = 25, 73%). The median number of pills used was 15 (0-48). Only 12 patients (36%) thought that they had been prescribed "too much" pain medication. Most patients reported receiving education about expectations for post-operative pain (n = 22, 69%); few recalled education about reducing or stopping opioids (n = 13, 40%). More than half of patients (n = 17, 53%) kept their leftover opioids rather than disposing of them or bringing them to an approved turn in location. CONCLUSIONS Despite most patients having leftover opioids following surgery, few patients recognized possible overprescription. Education regarding opioid use following surgery is inconsistent, potentially contributing to the amount of retained opioids currently available. Future guidelines should focus on determining the appropriate amount of opioids to be prescribed following surgery and standardizing and improving education given to patients.
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Affiliation(s)
- Anne P Ehlers
- Department of Surgery, University of Michigan, VA Ann Arbor Healthcare System 2210 Taubman Center, SPC 5343, Ann Arbor, MI, USA.
| | - Kevin M Sullivan
- Department of Surgery, University of Washington, Seattle, WA, USA
| | | | - John I Monu
- Department of Surgery, University of Washington, Seattle, WA, USA
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A Survey of Molecular Imaging of Opioid Receptors. Molecules 2019; 24:molecules24224190. [PMID: 31752279 PMCID: PMC6891617 DOI: 10.3390/molecules24224190] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Revised: 11/11/2019] [Accepted: 11/13/2019] [Indexed: 01/09/2023] Open
Abstract
The discovery of endogenous peptide ligands for morphine binding sites occurred in parallel with the identification of three subclasses of opioid receptor (OR), traditionally designated as μ, δ, and κ, along with the more recently defined opioid-receptor-like (ORL1) receptor. Early efforts in opioid receptor radiochemistry focused on the structure of the prototype agonist ligand, morphine, although N-[methyl-11C]morphine, -codeine and -heroin did not show significant binding in vivo. [11C]Diprenorphine ([11C]DPN), an orvinol type, non-selective OR antagonist ligand, was among the first successful PET tracers for molecular brain imaging, but has been largely supplanted in research studies by the μ-preferring agonist [11C]carfentanil ([11C]Caf). These two tracers have the property of being displaceable by endogenous opioid peptides in living brain, thus potentially serving in a competition-binding model. Indeed, many clinical PET studies with [11C]DPN or [11C]Caf affirm the release of endogenous opioids in response to painful stimuli. Numerous other PET studies implicate μ-OR signaling in aspects of human personality and vulnerability to drug dependence, but there have been very few clinical PET studies of μORs in neurological disorders. Tracers based on naltrindole, a non-peptide antagonist of the δ-preferring endogenous opioid enkephalin, have been used in PET studies of δORs, and [11C]GR103545 is validated for studies of κORs. Structures such as [11C]NOP-1A show selective binding at ORL-1 receptors in living brain. However, there is scant documentation of δ-, κ-, or ORL1 receptors in healthy human brain or in neurological and psychiatric disorders; here, clinical PET research must catch up with recent progress in radiopharmaceutical chemistry.
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Winterdahl M, Noer O, Orlowski D, Schacht AC, Jakobsen S, Alstrup AKO, Gjedde A, Landau AM. Sucrose intake lowers μ-opioid and dopamine D2/3 receptor availability in porcine brain. Sci Rep 2019; 9:16918. [PMID: 31729425 PMCID: PMC6858372 DOI: 10.1038/s41598-019-53430-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Accepted: 10/31/2019] [Indexed: 12/26/2022] Open
Abstract
Excessive sucrose consumption elicits addiction-like craving that may underpin the obesity epidemic. Opioids and dopamine mediate the rewarding effects of drugs of abuse, and of natural rewards from stimuli such as palatable food. We investigated the effects of sucrose using PET imaging with [11C]carfentanil (μ-opioid receptor agonist) and [11C]raclopride (dopamine D2/3 receptor antagonist) in seven female anesthetized Göttingen minipigs. We then gave minipigs access to sucrose solution for one hour on 12 consecutive days and performed imaging again 24 hours after the final sucrose access. In a smaller sample of five minipigs, we performed an additional [11C]carfentanil PET session after the first sucrose exposure. We calculated voxel-wise binding potentials (BPND) using the cerebellum as a region of non-displaceable binding, analyzed differences with statistical non-parametric mapping, and performed a regional analysis. After 12 days of sucrose access, BPND of both tracers had declined significantly in striatum, nucleus accumbens, thalamus, amygdala, cingulate cortex and prefrontal cortex, consistent with down-regulation of receptor densities. After a single exposure to sucrose, we found decreased binding of [11C]carfentanil in nucleus accumbens and cingulate cortex, consistent with opioid release. The lower availability of opioid and dopamine receptors may explain the addictive potential associated with intake of sucrose.
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Affiliation(s)
- Michael Winterdahl
- Department of Nuclear Medicine and PET Center, Aarhus University, Aarhus, Denmark
| | - Ove Noer
- Department of Nuclear Medicine and PET Center, Aarhus University, Aarhus, Denmark
| | - Dariusz Orlowski
- Department of Neurosurgery and CENSE, Aarhus University Hospital, Aarhus, Denmark
| | - Anna C Schacht
- Department of Nuclear Medicine and PET Center, Aarhus University, Aarhus, Denmark
| | - Steen Jakobsen
- Department of Nuclear Medicine and PET Center, Aarhus University, Aarhus, Denmark
| | - Aage K O Alstrup
- Department of Nuclear Medicine and PET Center, Aarhus University, Aarhus, Denmark
| | - Albert Gjedde
- Department of Nuclear Medicine and PET Center, Aarhus University, Aarhus, Denmark.,Department of Nuclear Medicine, University of Southern Denmark & Odense University Hospital, Odense, Denmark.,Department of Neuroscience, University of Copenhagen, Copenhagen, Denmark.,Department of Neurology and Neurosurgery, McGill University, Montreal, Canada
| | - Anne M Landau
- Department of Nuclear Medicine and PET Center, Aarhus University, Aarhus, Denmark. .,Translational Neuropsychiatry Unit, Aarhus University, Aarhus, Denmark.
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Brutman JN, Sirohi S, Davis JF. Recent Advances in the Neurobiology of Altered Motivation Following Bariatric Surgery. Curr Psychiatry Rep 2019; 21:117. [PMID: 31707546 DOI: 10.1007/s11920-019-1084-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
PURPOSE OF REVIEW There is compelling evidence in the clinical population that long-term weight loss secondary to bariatric surgery is mitigated by the reemergence of maladaptive feeding behaviors and in some cases new onset substance abuse. RECENT FINDINGS A review of the current literature suggests that physical restructuring of the GI tract during WLS alters secretion of feeding peptides and nutrient-sensing mechanisms that directly target the brain's endogenous reward system, the mesolimbic dopamine system. Post-surgical changes in GI physiology augment activation of the mesolimbic system. In some patients, this process may contribute to a reduced appetite for palatable food whereas in others it may support maladaptive motivated behavior for food and chemical drugs. It is concluded that future studies are required to detail the timing and duration of surgical-induced changes in GI-mesolimbic communication to more fully understand this phenomenon.
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Affiliation(s)
- Julianna N Brutman
- Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, 1815 Ferdinand's Lane, Pullman, WA, 99164, USA
| | - Sunil Sirohi
- Laboratory of Endocrine and Neuropsychiatric Disorders, Division of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, LA, USA
| | - Jon F Davis
- Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, 1815 Ferdinand's Lane, Pullman, WA, 99164, USA.
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37
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Nance K, Acevedo MB, Pepino MY. Changes in taste function and ingestive behavior following bariatric surgery. Appetite 2019; 146:104423. [PMID: 31473274 DOI: 10.1016/j.appet.2019.104423] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Revised: 07/22/2019] [Accepted: 08/23/2019] [Indexed: 02/06/2023]
Abstract
Bariatric surgery is the most effective treatment for severe obesity and its related comorbidities. Roux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG) are currently the most popular weight-loss surgeries used worldwide. Following these surgeries, many patients self-report changes in taste perception and decreased preference for unhealthy foods. These reported changes might account for increased adherence to healthier diets and successful weight loss after surgeries. However, researchers have used a variety of methodologies to assess patients' reported changes andresults are discrepant. The goal of this review is to summarize the literature regarding changes to taste function and ingestive behavior following RYGB and SG to examine differences in findings by methodology (indirect vs. direct measurements). We focused our review around changes in sweets, fats, and alcohol because most of the documented changes in ingestive behavior post-surgery are related to changes in these dietary items. We found that studies using surveys and questionnaires generally find that subjects self-report changes in taste and decrease their preference and cravings for energy-dense foods (particularly, sweets and high-fats). However, studies using validated sensory techniques that include oral sampling or by using direct food intake measurements find little to no change in subjects' ability to perceive taste or their preference for energy-dense foods. Therefore, reported changes in taste and food preferences are unlikely to be explained by alterations in taste intensity and diet selection, and are rather related to changes in the rewarding value of food. Further, that RYGB, and likely SG, is associated with increased alcohol consumption and arisk to develop an alcohol use disorder) supports the notion that these surgeries alter central circuits of reward that are critical in the regulation of ingestive behavior.
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Affiliation(s)
- Katie Nance
- Department of Food Science and Human Nutrition, College of Agricultural, Consumer and Environmental Sciences, University of Illinois, 905 South Goodwin Avenue, Urbana, IL, 61801, USA.
| | - M Belén Acevedo
- Department of Food Science and Human Nutrition, College of Agricultural, Consumer and Environmental Sciences, University of Illinois, 905 South Goodwin Avenue, Urbana, IL, 61801, USA.
| | - M Yanina Pepino
- Department of Food Science and Human Nutrition, College of Agricultural, Consumer and Environmental Sciences, University of Illinois, 905 South Goodwin Avenue, Urbana, IL, 61801, USA; Division of Nutritional Sciences, College of Agricultural, Consumer and Environmental Sciences, University of Illinois, 905 South Goodwin Avenue, Urbana, IL, 61801, USA.
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Roux-en-Y gastric bypass in rat reduces mu-opioid receptor levels in brain regions associated with stress and energy regulation. PLoS One 2019; 14:e0218680. [PMID: 31220174 PMCID: PMC6586324 DOI: 10.1371/journal.pone.0218680] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Accepted: 06/06/2019] [Indexed: 12/23/2022] Open
Abstract
Roux-en-Y gastric bypass surgery (RYGB) is the most common and effective weight loss procedure for severe obesity. However, a significant increase in addictive behaviors and new-onset substance use disorder (SUD) are sometimes observed post-surgery. The endogenous opioid system is known to play a major role in motivated behavior and reward, as well as the abuse of substances, including alcohol, tobacco, opioids and highly palatable foods. Here, we examined the effects of RYGB on mu-opioid receptor levels in the brain. Male Sprague-Dawley rats were assigned to one of four groups: standard diet with sham surgery (control), ad libitum high-energy high-fat (HF) diet with sham surgery, calorie restricted HF diet with sham surgery (Sham-FR), or HF diet with RYGB surgery. Control and HF groups were fed their respective diets for 8 weeks, with surgery performed on the eighth week. After 9 weeks on their respective diets post-surgery, animals were sacrificed for mu-opioid receptor autoradiography using the [3H] [D-Ala2,N-Me-Phe4-Gly5-ol]- enkephalin (DAMGO) ligand. Rats with RYGB showed reduced DAMGO binding in the central amygdala compared to sham-operated HF diet controls, and in the hypothalamus compared to high-fat fed Sham-FR. Diet alone did not change [3H] DAMGO binding in any region. These findings show that RYGB surgery, independent of diet or caloric restriction, decreases mu opioid signaling in specific regions important for stress and energy regulation. Thus, RYGB surgery may lead to greater stress sensitivity via downregulated mu opioid signaling in the central amygdala, which may contribute to the observed increased risk in some subjects for addictive behavior.
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Kure Liu C, Joseph PV, Feldman DE, Kroll DS, Burns JA, Manza P, Volkow ND, Wang GJ. Brain Imaging of Taste Perception in Obesity: a Review. Curr Nutr Rep 2019; 8:108-119. [PMID: 30945140 PMCID: PMC6486899 DOI: 10.1007/s13668-019-0269-y] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
PURPOSE OF REVIEW We summarize neuroimaging findings related to processing of taste (fat, salt, umami, bitter, and sour) in the brain and how they influence hedonic responses and eating behaviors and their role in obesity. RECENT FINDINGS Neuroimaging studies in obese individuals have revealed alterations in reward/motivation, executive control/self-regulation, and limbic/affective circuits that are implicated in food and drug addiction. Psychophysical studies show that sensory properties of food ingredients may be associated with anthropometric and neurocognitive outcomes in obesity. However, few studies have examined the neural correlates of taste and processing of calories and nutrient content in obesity. The literature of neural correlated of bitter, sour, and salty tastes remains sparse in obesity. Most published studies have focused on sweet, followed by fat and umami taste. Studies on calorie processing and its conditioning by preceding taste sensations have started to delineate a dynamic pattern of brain activation associated with appetition. Our expanded understanding of taste processing in the brain from neuroimaging studies is poised to reveal novel prevention and treatment targets to help address overeating and obesity.
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Affiliation(s)
- Christopher Kure Liu
- Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 10 Center Dr, Rm B2L124, Bethesda, MD 20892-1013 USA
| | - Paule Valery Joseph
- Sensory Science and Metabolism Unit, Biobehavioral Branch, National Institute of Nursing Research, National Institutes of Health, 31 Center Drive, Rm 5B03, Bethesda, MD 20892-2178 USA
| | - Dana E. Feldman
- Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 10 Center Dr, Rm B2L124, Bethesda, MD 20892-1013 USA
| | - Danielle S. Kroll
- Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 10 Center Dr, Rm B2L124, Bethesda, MD 20892-1013 USA
| | - Jamie A. Burns
- Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 10 Center Dr, Rm B2L124, Bethesda, MD 20892-1013 USA
| | - Peter Manza
- Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 10 Center Dr, Rm B2L124, Bethesda, MD 20892-1013 USA
| | - Nora D. Volkow
- Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 10 Center Dr, Rm B2L124, Bethesda, MD 20892-1013 USA
- National Institute on Drug Abuse, National Institutes of Health, 6001 Executive Blvd., Suite 5274, Bethesda, MD 20892-9581 USA
| | - Gene-Jack Wang
- Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 10 Center Dr, Rm B2L124, Bethesda, MD 20892-1013 USA
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40
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Postoperative Opioid Prescribing Practices and Evidence-Based Guidelines in Bariatric Surgery. Obes Surg 2019; 29:2030-2036. [DOI: 10.1007/s11695-019-03821-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Hamilton J, Swenson S, Hajnal A, Thanos PK. Roux-en-Y gastric bypass surgery normalizes dopamine D1, D2, and DAT levels. Synapse 2018; 72. [PMID: 29992624 DOI: 10.1002/syn.22058] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2018] [Revised: 06/28/2018] [Accepted: 07/05/2018] [Indexed: 02/28/2024]
Abstract
Roux-en-Y gastric bypass surgery (RYGB) is one of the most effective treatments for morbid obesity. However, increased substance abuse following RYGB has been observed clinically. This study examined the effects of RYGB on the dopamine system to elucidate these observed changes in reward-related behavior. Rats were assigned to four groups: normal diet with sham surgery, ad libitum high fat (HF) diet with sham surgery, restricted HF diet with sham surgery, and HF diet with RYGB surgery. Following surgeries, rats were kept on their respective diets for 9 weeks before they were sacrificed. [3 H]SCH 23390, [3 H]Spiperone, and [3 H]WIN35 428 autoradiography was performed to quantify the effects of diet and RYGB surgery on dopamine type 1-like receptor (D1R)-like, dopamine type 2-like receptor (D2R)-like, and dopamine transporter (DAT) binding. Rats on a chronic HF diet became obese with reduced D1R-like binding within the ventrolateral striatum and the nucleus accumbens core, reduced D2R-like binding in all areas of the striatum and nucleus accumbens core and shell, and reduced DAT binding in the dorsomedial striatum. Restricted HF diet rats showed similar reductions in D1R-like and D2-R-like binding as the obese rats, and reduced DAT binding within all areas of the striatum. Both RYGB and restricted HF diet rats showed similar weight reductions, with RYGB rats showing no difference in binding compared to controls. The observed changes in binding between non-treated obese rats and RYGB rats demonstrates that HF dietary effects on the dopamine system were reversed by RYGB.
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Affiliation(s)
- John Hamilton
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA), Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, University at Buffalo, Buffalo, New York
- Department of Psychology, University of Buffalo, Buffalo, New York
| | - Sabrina Swenson
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA), Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, University at Buffalo, Buffalo, New York
| | - Andras Hajnal
- Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania
| | - Panayotis K Thanos
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA), Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, University at Buffalo, Buffalo, New York
- Department of Psychology, University of Buffalo, Buffalo, New York
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42
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Saanijoki T, Nummenmaa L, Tuulari JJ, Tuominen L, Arponen E, Kalliokoski KK, Hirvonen J. Aerobic exercise modulates anticipatory reward processing via the μ-opioid receptor system. Hum Brain Mapp 2018; 39:3972-3983. [PMID: 29885086 DOI: 10.1002/hbm.24224] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2018] [Revised: 04/20/2018] [Accepted: 05/10/2018] [Indexed: 01/18/2023] Open
Abstract
Physical exercise modulates food reward and helps control body weight. The endogenous µ-opioid receptor (MOR) system is involved in rewarding aspects of both food and physical exercise, yet interaction between endogenous opioid release following exercise and anticipatory food reward remains unresolved. Here we tested whether exercise-induced opioid release correlates with increased anticipatory reward processing in humans. We scanned 24 healthy lean men after rest and after a 1 h session of aerobic exercise with positron emission tomography (PET) using MOR-selective radioligand [11 C]carfentanil. After both PET scans, the subjects underwent a functional magnetic resonance imaging (fMRI) experiment where they viewed pictures of palatable versus nonpalatable foods to trigger anticipatory food reward responses. Exercise-induced changes in MOR binding in key regions of reward circuit (amygdala, thalamus, ventral and dorsal striatum, and orbitofrontal and cingulate cortices) were used to predict the changes in anticipatory reward responses in fMRI. Exercise-induced changes in MOR binding correlated negatively with the exercise-induced changes in neural anticipatory food reward responses in orbitofrontal and cingulate cortices, insula, ventral striatum, amygdala, and thalamus: higher exercise-induced opioid release predicted higher brain responses to palatable versus nonpalatable foods. We conclude that MOR activation following exercise may contribute to the considerable interindividual variation in food craving and consumption after exercise, which might promote compensatory eating and compromise weight control.
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Affiliation(s)
| | - Lauri Nummenmaa
- Turku PET Centre, University of Turku, Turku, Finland.,Department of Psychology, University of Turku, Turku, Finland
| | | | - Lauri Tuominen
- Turku PET Centre, University of Turku, Turku, Finland.,Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts.,Harvard Medical School, Boston, Massachusetts
| | | | | | - Jussi Hirvonen
- Turku PET Centre, University of Turku, Turku, Finland.,Department of Radiology, Turku University Hospital, Turku, Finland
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Nummenmaa L, Saanijoki T, Tuominen L, Hirvonen J, Tuulari JJ, Nuutila P, Kalliokoski K. μ-opioid receptor system mediates reward processing in humans. Nat Commun 2018; 9:1500. [PMID: 29662095 PMCID: PMC5902580 DOI: 10.1038/s41467-018-03848-y] [Citation(s) in RCA: 79] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2017] [Accepted: 03/16/2018] [Indexed: 12/19/2022] Open
Abstract
The endogenous μ-opioid receptor (MOR) system regulates motivational and hedonic processing. We tested directly whether individual differences in MOR are associated with neural reward responses to food pictures in humans. We scanned 33 non-obese individuals with positron emission tomography (PET) using the MOR-specific radioligand [11C]carfentanil. During a functional magnetic resonance imaging (fMRI) scan, the subjects viewed pictures of appetizing versus bland foods to elicit reward responses. MOR availability was measured in key components of the reward and emotion circuits and used to predict BOLD-fMRI responses to foods. Viewing palatable versus bland foods activates regions involved in homeostatic and reward processing, such as amygdala, ventral striatum, and hypothalamus. MOR availability in the reward and emotion circuit is negatively associated with the fMRI reward responses. Variation in MOR availability may explain why some people feel an urge to eat when encountering food cues, increasing risk for weight gain and obesity. μ-opioid signalling has a known role in the response to various rewarding stimuli, including pleasant foods. Here, Nummenmaa et al. show using PET and fMRI that individual differences in brain μ-opioid receptor density predict the strength of the neural response to highly palatable foods in humans
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Affiliation(s)
- Lauri Nummenmaa
- Turku PET Centre, University of Turku and Turku University Hospital, 20520, Turku, Finland. .,Department of Psychology, University of Turku, 20014, Turku, Finland.
| | - Tiina Saanijoki
- Turku PET Centre, University of Turku and Turku University Hospital, 20520, Turku, Finland
| | - Lauri Tuominen
- Turku PET Centre, University of Turku and Turku University Hospital, 20520, Turku, Finland
| | - Jussi Hirvonen
- Turku PET Centre, University of Turku and Turku University Hospital, 20520, Turku, Finland.,Department of Radiology, University of Turku, 20014, Turku, Finland
| | - Jetro J Tuulari
- Turku PET Centre, University of Turku and Turku University Hospital, 20520, Turku, Finland
| | - Pirjo Nuutila
- Turku PET Centre, University of Turku and Turku University Hospital, 20520, Turku, Finland
| | - Kari Kalliokoski
- Turku PET Centre, University of Turku and Turku University Hospital, 20520, Turku, Finland
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Noradrenaline transporter availability on [ 11C]MRB PET predicts weight loss success in highly obese adults. Eur J Nucl Med Mol Imaging 2018; 45:1618-1625. [PMID: 29627935 DOI: 10.1007/s00259-018-4002-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2017] [Accepted: 03/22/2018] [Indexed: 12/28/2022]
Abstract
PURPOSE Although the mechanisms by which the central noradrenaline (NA) system influences appetite and controls energy balance are quite well understood, its relationship to changes in body weight remains largely unknown. The main goal of this study was to further clarify whether the brain NA system is a stable trait or whether it can be altered by dietary intervention. METHODS We aimed to compare central NA transporter (NAT) availability in ten obese, otherwise healthy individuals with a body mass index (BMI) of 42.4 ± 3.7 kg/m2 (age 34 ± 9 years, four women) and ten matched non-obese, healthy controls (BMI 23.9 ± 2.5 kg/m2, age 33 ± 10 years, four women) who underwent PET with the NAT-selective radiotracer (S,S)-[11C]O-methylreboxetine (MRB) before and 6 months after dietary intervention. RESULTS MRI-based individual volume-of-interest analyses revealed an increase in binding potential (BPND) in the insula and the hippocampus of obese individuals, which correlated well with changes in BMI (-3.3 ± 5.3%; p = 0.03) following completion of the dietary intervention. Furthermore, voxel-wise regression analyses showed that lower BPND in these regions, but also in the midbrain and the prefrontal cortex, at baseline was associated with higher achieved weight loss (e.g., hippocampal area R2 = 0.80; p < 0.0001). No changes were observed in non-obese controls. CONCLUSION These first longitudinal interventional data on NAT availability in highly obese individuals indicate that the central NA system is modifiable. Our findings suggest that NAT availability before intervention could help predict the amount and success of weight loss in obese individuals and help adjust treatment options individually by allowing prediction of the benefit of a dietary intervention.
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45
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Hankir MK, Seyfried F, Miras AD, Cowley MA. Brain Feeding Circuits after Roux-en-Y Gastric Bypass. Trends Endocrinol Metab 2018; 29:218-237. [PMID: 29475578 DOI: 10.1016/j.tem.2018.01.009] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2017] [Revised: 01/17/2018] [Accepted: 01/25/2018] [Indexed: 12/12/2022]
Abstract
Metabolic surgical procedures, such as Roux-en-Y gastric bypass (RYGB), uniquely reprogram feeding behavior and body weight in obese subjects. Clinical neuroimaging and animal studies are only now beginning to shed light on some of the underlying central mechanisms. We present here the roles of key brain neurotransmitter/neuromodulator systems in food choice, value, and intake at various stages after RYGB. In doing so, we elaborate on how known signals emanating from the reorganized gut, including peptide hormones and microbiota products, impinge on newly mapped homeostatic and hedonic brain feeding circuits. Continued progress in the rapidly evolving field of metabolic surgery will inform the design of more effective weight-loss compounds.
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Affiliation(s)
- Mohammed K Hankir
- Department of Experimental Surgery, University Hospital Wuerzburg, Wuerzburg, Bavaria 97080, Germany; German Research Foundation Collaborative Research Center in Obesity Mechanisms, University of Leipzig, Leipzig, Saxony 04103, Germany.
| | - Florian Seyfried
- Department of Experimental Surgery, University Hospital Wuerzburg, Wuerzburg, Bavaria 97080, Germany
| | - Alexander D Miras
- Department of Investigative Science, Imperial College London Academic Healthcare Centre, London W12 0NN, UK
| | - Michael A Cowley
- Metabolic Disease and Obesity Program, Biomedicine Discovery Institute, Monash University, Victoria 3800, Australia; Department of Physiology, Monash University, Victoria 3800, Australia
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Abstract
This paper is the thirty-ninth consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2016 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior, and the roles of these opioid peptides and receptors in pain and analgesia, stress and social status, tolerance and dependence, learning and memory, eating and drinking, drug abuse and alcohol, sexual activity and hormones, pregnancy, development and endocrinology, mental illness and mood, seizures and neurologic disorders, electrical-related activity and neurophysiology, general activity and locomotion, gastrointestinal, renal and hepatic functions, cardiovascular responses, respiration and thermoregulation, and immunological responses.
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Affiliation(s)
- Richard J Bodnar
- Department of Psychology and CUNY Neuroscience Collaborative, Queens College, City University of New York, Flushing, NY 11367, United States.
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47
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Thobois S, Brefel-Courbon C, Le Bars D, Sgambato-Faure V. Molecular Imaging of Opioid System in Idiopathic Parkinson's Disease. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2018; 141:275-303. [DOI: 10.1016/bs.irn.2018.07.029] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Raghow R. Gut-brain crosstalk regulates craving for fatty food. World J Diabetes 2017; 8:484-488. [PMID: 29290921 PMCID: PMC5740093 DOI: 10.4239/wjd.v8.i12.484] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2017] [Revised: 07/20/2017] [Accepted: 09/04/2017] [Indexed: 02/05/2023] Open
Abstract
Patients undergoing Roux-en-Y gastric bypass (RYGB) surgery elicit striking loss of body weight. Anatomical re-structuring of the gastrointestinal (GI) tract, leading to reduced caloric intake and changes in food preference, are thought to be the primary drivers of weight loss in bariatric surgery patients. However, the mechanisms by which RYGB surgery causes a reduced preference for fatty foods remain elusive. In a recent report, Hankir et al described how RYGB surgery modulated lipid nutrient signals in the intestine of rats to blunt their craving for fatty food. The authors reported that RYGB surgery restored an endogenous fat-satiety signaling pathway, mediated via oleoylethanolamide (OEA), that was greatly blunted in obese animals. In RYGB rats, high fat diet (HFD) led to increased production of OEA that activated the intestinal peroxisome proliferation activator receptors-α (PPARα). In RYGB rats, activation of PPARα by OEA was accompanied by enhanced dopamine neurotransmission in the dorsal striatum and reduced preference for HFD. The authors showed that OEA-mediated signals to the midbrain were transmitted via the vagus nerve. Interfering with either the production of OEA in enterocytes, or blocking of vagal and striatal D1 receptors signals eliminated the decreased craving for fat in RYGB rats. These studies demonstrated that bariatric surgery led to alterations in the reward circuitry of the brain in RYGB rats and reduced their preference for HFD.
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Affiliation(s)
- Rajendra Raghow
- Department of Veterans Affairs Medical Center, Memphis, TN 38104, United States
- Department of Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163, United States
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Pekkarinen T, Mustonen H, Sane T, Jaser N, Juuti A, Leivonen M. Long-Term Effect of Gastric Bypass and Sleeve Gastrectomy on Severe Obesity: Do Preoperative Weight Loss and Binge Eating Behavior Predict the Outcome of Bariatric Surgery? Obes Surg 2017; 26:2161-2167. [PMID: 26843084 DOI: 10.1007/s11695-016-2090-7] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND Few studies have examined weight loss sustainability after sleeve gastrectomy (SG). The purpose of this study was to determine long-term outcome after SG and gastric bypass (GBP) and learn whether preoperative weight loss and binge eating behavior can be used to predict outcome. MATERIALS AND METHODS Together, 257 patients (64 % women) were operated, 163 by GBP and 94 by SG. Binge eating was assessed by binge eating scale (BES) and preoperative weight loss was advised to all, including very low-calorie diet for 5 weeks. Postoperative visits took place at 1 and 2 years, and long-term outcome was at median 5 years (range 2.29-6.85). Multivariate linear regression analysis was used to predict outcome at 2-year and long-term control. RESULTS Median age was 48 years, weight 141.1 kg, and BMI 48.2 kg/m(2). Preoperative weight loss was median 4.9 % before GBP and 3.8 % before SG, P = 0.04. Total weight loss at year one was 24.1 % in GBP and 23.7 % in SG (P = 0.40), at year two 24.4 and 23.4 % (P = 0.26), and at long-term control 23.0 and 20.2 % (P = 0.006), respectively. Weight was analyzed in 93, 88, and 89 % of those alive, respectively. BES did not predict weight outcome, but larger preoperative weight loss predicted less postoperative weight loss at 2 years. CONCLUSION On long term, weight loss was better maintained after GBP compared with SG. Binge eating behavior was not a significant predictor, but larger preoperative weight loss predicted less postoperative weight loss for the next 2 years.
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Affiliation(s)
- Tuula Pekkarinen
- Abdominal Center, Peijas Hospital, Helsinki University Hospital, P.O. Box 900, FIN-00029 HUS, Vantaa, Finland.
| | - Harri Mustonen
- University of Helsinki and Helsinki University Hospital, P.O. Box 440, FIN-00029 HUS, Helsinki, Finland
| | - Timo Sane
- Abdominal Center, Meilahti Hospital, Helsinki University Hospital, P.O. Box 340, FIN-00029 HUS, Helsinki, Finland
| | - Nabil Jaser
- Abdominal Center, Peijas Hospital, Helsinki University Hospital, P.O. Box 900, FIN-00029 HUS, Vantaa, Finland
| | - Anne Juuti
- Abdominal Center, Peijas Hospital, Helsinki University Hospital, P.O. Box 900, FIN-00029 HUS, Vantaa, Finland
| | - Marja Leivonen
- Abdominal Center, Peijas Hospital, Helsinki University Hospital, P.O. Box 900, FIN-00029 HUS, Vantaa, Finland
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50
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Caravaggio F, Ku Chung J, Plitman E, Boileau I, Gerretsen P, Kim J, Iwata Y, Patel R, Chakravarty MM, Remington G, Graff-Guerrero A. The relationship between subcortical brain volume and striatal dopamine D 2/3 receptor availability in healthy humans assessed with [ 11 C]-raclopride and [ 11 C]-(+)-PHNO PET. Hum Brain Mapp 2017; 38:5519-5534. [PMID: 28752565 DOI: 10.1002/hbm.23744] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Revised: 06/21/2017] [Accepted: 07/16/2017] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND Abnormalities in dopamine (DA) and brain morphology are observed in several neuropsychiatric disorders. However, it is not fully understood how these abnormalities may relate to one another. For such in vivo findings to be used as biomarkers for neuropsychiatric disease, it must be understood how variability in DA relates to brain structure under healthy conditions. We explored how the availability of striatal DA D2/3 receptors (D2/3 R) is related to the volume of subcortical brain structures in a sample of healthy humans. Differences in D2/3 R availability measured with an antagonist radiotracer ([11 C]-raclopride) versus an agonist radiotracer ([11 C]-(+)-PHNO) were examined. METHODS Data from 62 subjects scanned with [11 C]-raclopride (mean age = 38.98 ± 14.45; 23 female) and 68 subjects scanned with [11 C]-(+)-PHNO (mean age = 38.54 ± 14.59; 25 female) were used. Subcortical volumes were extracted from T1-weighted images using the Multiple Automatically Generated Templates (MAGeT-Brain) algorithm. Partial correlations were used controlling for age, gender, and total brain volume. RESULTS For [11 C]-(+)-PHNO, ventral caudate volumes were positively correlated with BPND in the dorsal caudate and globus pallidus (GP). Ventral striatum (VS) volumes were positively correlated with BPND in the VS. With [11 C]-raclopride, BPND in the VS was negatively correlated with subiculum volume of the hippocampus. Moreover, BPND in the GP was negatively correlated with the volume of the lateral posterior nucleus of the thalamus. CONCLUSION Findings are purely exploratory and presented corrected and uncorrected for multiple comparisons. We hope they will help inform the interpretation of future PET studies where concurrent changes in D2/3 R and brain morphology are observed. Hum Brain Mapp 38:5519-5534, 2017. © 2017 Wiley Periodicals, Inc.
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Affiliation(s)
- Fernando Caravaggio
- Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8, Canada.,Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8, Canada
| | - Jun Ku Chung
- Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8, Canada
| | - Eric Plitman
- Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8, Canada
| | - Isabelle Boileau
- Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8, Canada.,Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8, Canada
| | - Philip Gerretsen
- Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8, Canada.,Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8, Canada
| | - Julia Kim
- Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8, Canada
| | - Yusuke Iwata
- Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8, Canada.,Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8, Canada
| | - Raihaan Patel
- Department of Biological & Biomedical Engineering, McGill University, Montreal, Quebec, H4H 1R3, Canada.,Cerebral Imaging Centre, Douglas Mental Health Institute, McGill University, Montreal, Quebec, H4H 1R3, Canada
| | - M Mallar Chakravarty
- Department of Biological & Biomedical Engineering, McGill University, Montreal, Quebec, H4H 1R3, Canada.,Cerebral Imaging Centre, Douglas Mental Health Institute, McGill University, Montreal, Quebec, H4H 1R3, Canada.,Department of Psychiatry, McGill University, Montreal, Quebec, H4H 1R3, Canada
| | - Gary Remington
- Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8, Canada.,Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8, Canada
| | - Ariel Graff-Guerrero
- Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8, Canada.,Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8, Canada
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