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Miller-Matero LR, Vanderziel A, Haley EN, Jackson KM, Moore RS, Hamann A, Carlin AM, Genaw J, Braciszewski JM. Alcohol use after metabolic and bariatric surgery: a qualitative investigation of the relation with mood and food. Health Psychol Behav Med 2025; 13:2478029. [PMID: 40098646 PMCID: PMC11912293 DOI: 10.1080/21642850.2025.2478029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Accepted: 03/02/2025] [Indexed: 03/19/2025] Open
Abstract
Background Individuals who undergo metabolic and bariatric surgery are at increased risk for an alcohol use disorder. Clarity on the relationships between mood, food, and alcohol use could inform interventions to reduce alcohol use and mitigate risk of alcohol use disorders after metabolic and bariatric surgery (MBS). Methods Twenty patients who underwent MBS at a single health care system and reported engaging in post-operative alcohol use were recruited. Participants were between 6 months and 3 years post-operative and reported consuming alcohol at least 2-3 times per month. Participants engaged in a 1-hour semi-structured interview about factors influencing post-operative mood, eating behaviors, and alcohol use. All interviews were recorded, transcribed, and coded by two independent raters. Results Statements by participants were deductively coded within different themes: (1) changes in mood, (2) changes in eating patterns, and (3) unintended alcohol use and eating. Participants reported positive changes in mood and eating behaviors following MBS, but also indicated potential for negative mood states and new eating patterns. They also suggested that mood was a driver of both eating and alcohol use, including unintended (i.e. unplanned) eating and unintended alcohol use. However, most did not consume food and alcohol at the same time. Discussion Food and alcohol may be used as a coping strategy for mood, though they are not often consumed together. There is currently a lack of post-operative interventions to reduce alcohol use and findings suggest that interventions could simultaneously target mood, unintended eating, and alcohol use.
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Affiliation(s)
- Lisa R. Miller-Matero
- Behavioral Health, Henry Ford Health, Detroit, MI, USA
- Center for Health Policy and Health Services Research, Henry Ford Health, Detroit, MI, USA
- College of Human Medicine, Michigan State University, East Lansing, MI, USA
| | - Alyssa Vanderziel
- Center for Health Policy and Health Services Research, Henry Ford Health, Detroit, MI, USA
- College of Human Medicine, Michigan State University, East Lansing, MI, USA
| | - Erin N. Haley
- Center for Health Policy and Health Services Research, Henry Ford Health, Detroit, MI, USA
- College of Human Medicine, Michigan State University, East Lansing, MI, USA
| | - Kristina M. Jackson
- Department of Psychiatry, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA
| | - Roland S. Moore
- Pacific Institute for Research and Evaluation, Berkeley, CA, USA
| | - Aaron Hamann
- Behavioral Health, Henry Ford Health, Detroit, MI, USA
- Department of Surgery, Henry Ford Health, Detroit, MI, USA
| | | | - Jeffrey Genaw
- Department of Surgery, Henry Ford Health, Detroit, MI, USA
| | - Jordan M. Braciszewski
- Behavioral Health, Henry Ford Health, Detroit, MI, USA
- Center for Health Policy and Health Services Research, Henry Ford Health, Detroit, MI, USA
- College of Human Medicine, Michigan State University, East Lansing, MI, USA
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Speed SN, Sherman GT, Wang T, Pince CL, Sanfilippo JE, Montemitro C, Giorgi S, Curtis BL, Farinelli LA, Farokhnia M, Leggio L. Bariatric surgery and alcohol and substance use: A case-control survey study. Drug Alcohol Depend 2025; 267:112529. [PMID: 39764929 PMCID: PMC11780309 DOI: 10.1016/j.drugalcdep.2024.112529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 12/13/2024] [Accepted: 12/15/2024] [Indexed: 01/25/2025]
Abstract
PURPOSE Studies suggest alcohol and/or other substance misuse may develop after bariatric surgery (BS), but findings are not consistent or conclusive. PROCEDURES This cross-sectional online survey investigated alcohol and other substance use, via a modified version of the Alcohol Use Disorders Identification Test, before and after bariatric surgery, compared to a non-bariatric surgery sample. Data were anonymously collected via Qualtrics from adults who reported alcohol or substance use (BS, n = 328; non-BS, n = 292). FINDINGS Problematic alcohol, opioid, amphetamine, and cannabis use were reduced post-surgery compared to pre-surgery. After surgery, participants expressed "guilt" associated with alcohol and other substance use (average 0.24 and 0.31 points higher, respectively) compared to pre-surgery. Compared to controls, the bariatric surgery group reported on average 1.99 points less problematic nicotine use pre-surgery (p = .012) and 2.42 points less post-surgery (p = .004). In contrast, compared to people without any history of bariatric surgery, the bariatric surgery group reported greater problematic use of alcohol, cannabis, hallucinogens, and/or inhalants pre-surgery (all p < .001); same results were found post-surgery for all drugs, (all p < .001) except for hallucinogens which was not significantly different between the two groups. RELEVANCE Unlike previous reports, these survey-based results do not show an increase in problematic alcohol and substance use following bariatric surgery. Recall biases and the survey-based methodology are however important limitations of the present study. The observed increase in "guilt" associated with substance use may align with growing evidence suggesting increased subjective response to alcohol and other substances following bariatric surgery.
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Affiliation(s)
- Shannon N Speed
- Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Bethesda, Baltimore, MD, USA
| | - Garrick T Sherman
- Office of the Clinical Director, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, USA
| | - Tammy Wang
- Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Bethesda, Baltimore, MD, USA
| | - Claire L Pince
- Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Bethesda, Baltimore, MD, USA
| | - Jenna E Sanfilippo
- Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Bethesda, Baltimore, MD, USA
| | - Chiara Montemitro
- Center for Social and Affective Neuroscience. Linköping University, Linköping, Sweden
| | - Salvatore Giorgi
- Technology and Translational Research Unit, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, USA
| | - Brenda L Curtis
- Technology and Translational Research Unit, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, USA
| | - Lisa A Farinelli
- Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Bethesda, Baltimore, MD, USA
| | - Mehdi Farokhnia
- Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Bethesda, Baltimore, MD, USA
| | - Lorenzo Leggio
- Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Bethesda, Baltimore, MD, USA.
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Lefere S, Troisi RI, Karam V, Fondevila C, Nevens F, Verbeek J, Detry O, Lanthier N, Serenari M, Wiering L, Vanwolleghem T, Moreno C, Berrevoet F, Geerts A. The Clinical Relevance of Prior Metabolic and Bariatric Surgery in Alcohol-Related Liver Disease in a Nationwide Belgian Liver Transplant Population. Liver Int 2025; 45:e16219. [PMID: 39699872 DOI: 10.1111/liv.16219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 11/16/2024] [Accepted: 12/04/2024] [Indexed: 12/20/2024]
Abstract
BACKGROUND AND AIMS Patients with a history of metabolic and bariatric surgery (MBS) are susceptible to developing alcohol use disorder. Outcome after transplantation for alcohol-related liver disease (ALD) has not been studied in-depth. METHODS We included adult patients who underwent a liver transplantation (LT) in Belgium between 1 January 2013 and 31 December 2022 for ALD. We captured all patients with a history of MBS prior to developing ALD, and included non-MBS patients for comparison. RESULTS We identified 39 patients who underwent MBS before developing ALD, and included 443 non-MBS patients with an LT for ALD as controls. The median time between MBS and diagnosis of severe liver disease was 7.2 years. MBS patients were 9 years younger at the time of transplantation (p < 0.001). Pre-LT hepatocellular carcinoma was more prevalent in the non-MBS group (p < 0.001), while severe bacterial infections occurred more frequently in those with prior MBS. Importantly, patients with MBS had a lower survival after LT in age- and sex-adjusted Cox regression analysis (HR 2.205, p = 0.023). Liver disease was listed in 70.0% versus 13.3% of patients as the main cause of death. Liver-related mortality was linked to alcohol use relapse post-LT, with significantly more MBS patients experiencing relapse (30.8% vs. 13.3%, p = 0.003). CONCLUSION Following MBS, excessive alcohol use can progress to end-stage ALD and need for LT. These patients present at a younger age, with more signs of hepatic decompensation, and can be at a higher risk for post-LT mortality, especially liver-related death.
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Affiliation(s)
- Sander Lefere
- Hepatology Research Unit, Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Liver Research Center Ghent, Ghent University, Ghent University Hospital, Ghent, Belgium
| | - Roberto Ivan Troisi
- Division of HBP, Minimally Invasive and Robotic Surgery, Transplantation Service, Federico II University Hospital, Naples, Italy
| | - Vincent Karam
- European Society for Organ Transplantation, Padova, Italy
| | - Constantino Fondevila
- Department of General and Digestive Surgery, Hospital Universitario La Paz, CiberEHD, Madrid, Spain
| | - Frederik Nevens
- Department of Hepatology, University Hospital Leuven, Leuven, Belgium
| | - Jef Verbeek
- Department of Hepatology, University Hospital Leuven, Leuven, Belgium
| | - Olivier Detry
- Department of Abdominal Surgery and Transplantation, CHU Liege, University of Liege, Liege, Belgium
| | - Nicolas Lanthier
- Service d'Hépato-gastroentérologie, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium
| | - Matteo Serenari
- Hepato-Biliary and Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Leke Wiering
- Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany
| | - Thomas Vanwolleghem
- Division of Gastroenterology and Hepatology, University Hospital Antwerp, Antwerp, Belgium
- Viral Hepatitis Research Group, Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Antwerp, Belgium
| | - Christophe Moreno
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
| | - Frederik Berrevoet
- Department of General and Hepatobiliary Surgery and Liver Transplantation, Ghent University Hospital, Ghent, Belgium
| | - Anja Geerts
- Hepatology Research Unit, Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Liver Research Center Ghent, Ghent University, Ghent University Hospital, Ghent, Belgium
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Richardson RS, Gomez JL, Vendruscolo LF, Leggio L, Ryabinin AE. Centrally administered growth hormone secretagogue receptor antagonist DLys decreases alcohol intake and preference in male mice. Neuroreport 2024; 35:909-914. [PMID: 39166385 PMCID: PMC11501076 DOI: 10.1097/wnr.0000000000002078] [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] [Indexed: 08/22/2024]
Abstract
Alcohol use disorder (AUD) is a highly prevalent public health problem. The ghrelin system has been identified as a potential target for therapeutic intervention for AUD. Previous work showed that systemic administration of the growth hormone secretagogue receptor (GHSR) antagonist DLys reduced alcohol intake and preference in male mice. Yet, it is unclear whether central or peripheral GHSRs mediated these effects. We hypothesized that alcohol consumption is driven by central GHSRs and addressed this hypothesis by testing the effects of central administration of DLys. Male C57BL/6J mice consumed alcohol in a two-bottle choice procedure (10% ethanol versus water). DLys (2 nmol) was administered intracerebroventricularly for 7 days to examine alcohol intake and preference. DLys decreased alcohol intake and preference but had no effect on food intake. The effects on alcohol intake and preference persisted after several administrations, indicating lack of tolerance to DLys' effects. These results suggest that central administration of DLys is sufficient to reduce alcohol drinking and that DLys remains effective after several administrations when given intracerebroventricularly. Moreover, this work suggests that the effects of intracerebroventricularly administered DLys are specific to alcohol and do not generalize to other calorie-driven behaviors.
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Affiliation(s)
- Rani S. Richardson
- Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore, MD, USA
- Neurobiology of Addiction Section, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD, USA
- University of North Carolina School of Medicine MD/PhD Program, University of North Carolina, Chapel Hill, NC, USA
- Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC, USA
- Stress and Addiction Neuroscience Unit, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore, MD, USA
| | - Juan L. Gomez
- Biobehavioral Imaging and Molecular Neuropsychopharmacology Unit, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, USA
- Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA
| | - Leandro F. Vendruscolo
- Stress and Addiction Neuroscience Unit, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore, MD, USA
| | - Lorenzo Leggio
- Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore, MD, USA
- Department of Behavioral and Social Sciences, Center for Alcohol and Addiction Studies, Brown University, Providence, RI, USA
- Division of Addiction Medicine, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
- Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA
| | - Andrey E. Ryabinin
- Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA
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Jerlhag E. Ghrelin system and GLP-1 as potential treatment targets for alcohol use disorder. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2024; 178:401-432. [PMID: 39523062 DOI: 10.1016/bs.irn.2024.07.006] [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: 11/16/2024]
Abstract
Peptides of the gut-brain axis have gained recent attention as potential treatment targets for addiction. While the number of gut-brain peptides is vast, ghrelin and glucagon-like peptide-1 (GLP-1) have been suggested as important players. Ghrelin is traditionally considered an orexigenic peptide, but recent studies found that it increases alcohol intake in rodents and craving for alcohol in humans. Additionally, suppression of the ghrelin receptor attenuates alcohol-related responses in animal models reflecting alcohol use disorder (AUD). For instance, a lower alcohol intake, suppressed motivation to consume alcohol, and attenuated reward from alcohol is observed after ghrelin receptor antagonism treatment. On a similar note, a partial ghrelin receptor agonist prevents hangover symptoms in humans. When it comes to the anorexigenic peptide GLP-1, agonists of its receptor are approved to treat diabetes type 2 and obesity. Extensive preclinical studies have revealed that these GLP-1 receptor agonists reduce alcohol intake, suppress the motivation to consume alcohol, and prevent relapse drink, with effects tentatively associated with a reduced alcohol-induced reward. These preclinical findings have to some extent been varied in humans, as GLP-1 receptor agonists decrease alcohol intake in overweight patients with AUD. Furthermore, genetic variations in either the genes encoding for pre-pro-ghrelin, GHSR, GLP-1, or its receptor, are associated with AUD and heavy alcohol drinking. While central mechanisms appear to modulate the ability of either ghrelin or GLP-1 to regulate alcohol-related responses the exact mechanisms have not been defined. Taken together these preclinical and clinical data imply that gut-brain peptides participate in the addiction process and should be considered as potential targets for AUD treatment.
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Affiliation(s)
- Elisabet Jerlhag
- Institute of Neuroscience and Physiology, Department of Pharmacology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
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Cooper KM, Colletta A, Hebda N, Devuni D. Alcohol associated liver disease and bariatric surgery: Current perspectives and future directions. World J Gastrointest Surg 2024; 16:650-657. [PMID: 38577096 PMCID: PMC10989338 DOI: 10.4240/wjgs.v16.i3.650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Revised: 01/27/2024] [Accepted: 02/26/2024] [Indexed: 03/22/2024] Open
Abstract
Bariatric surgery is a routinely performed procedure and is associated with a reduction in all-cause mortality in patients with obesity. However, bariatric surgery has also been linked to increased alcohol use with up to 30% of these patients developing alcohol use disorder (AUD). The mechanism of AUD after bariatric surgery is multifactorial and includes anatomic, metabolic, and neurohumoral changes associated with post-surgical anatomy. These patients are at increased risk of alcohol associated liver disease and, in some cases, require liver transplantation. In this article, we provide a scoping review of epidemiology, pathophysiology, and clinical outcomes of alcohol-related health conditions after bariatric surgery.
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Affiliation(s)
- Katherine M Cooper
- Department of Medicine, UMass Chan Medical School, Worcester, MA 01655, United States
| | - Alessandro Colletta
- Department of Medicine, UMass Chan Medical School, Worcester, MA 01655, United States
| | - Nicholas Hebda
- Department of Medicine, UMass Chan Medical School, Worcester, MA 01655, United States
| | - Deepika Devuni
- Department of Medicine, UMass Chan Medical School, Worcester, MA 01655, United States
- Division of Gastroenterology, UMass Chan Medical School, Worcester, MA 01655, United States
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Keller BN, Snyder AE, Coker CR, Aguilar EA, O’Brien MK, Bingaman SS, Arnold AC, Hajnal A, Silberman Y. Vagus nerve damage increases alcohol intake and preference in a nonpreferring rat line: Relationship to vagal regulation of the hypothalamic-pituitary-adrenal axis. ALCOHOL, CLINICAL & EXPERIMENTAL RESEARCH 2024; 48:488-498. [PMID: 38311347 PMCID: PMC10939901 DOI: 10.1111/acer.15264] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 12/12/2023] [Accepted: 12/28/2023] [Indexed: 02/10/2024]
Abstract
BACKGROUND Clinical and preclinical research indicates that gastric weight loss surgeries, such as Roux-en-Y gastric bypass surgery, can induce alcohol use disorder (AUD). While numerous mechanisms have been proposed for these effects, one relatively unexplored potential mechanism is physical damage to the gastric branch of the vagus nerve, which can occur during bypass surgery. Therefore, we hypothesized that direct damage to the gastric branch of the vagus nerve, without altering other aspects of gastric anatomy, could result in increased alcohol intake. METHODS To test this hypothesis, we compared alcohol intake and preference in multiple models in male Sprague-Dawley rats that received selective gastric branch vagotomy (VX) with rats who underwent sham surgery. Because the vagus nerve regulates hypothalamic-pituitary-adrenal (HPA) axis function, and alterations to HPA function are critical to the escalation of non-dependent alcohol intake, we also tested the hypothesis that gastric VX increases HPA function. RESULTS We found that VX increases alcohol intake and preference in the every-other-day, two-bottle choice test and increases preference for 1 g/kg alcohol in the conditioned place preference test. The effects were selective for alcohol, as sucrose intake and preference were not altered by VX. We also found that VX increases corticotropin releasing factor (CRF) mRNA in the paraventricular nucleus of the hypothalamus (PVN), increases putative PVN CRF neuronal action potential firing, and increases corticosterone levels. CONCLUSIONS Overall, these findings suggest that the vagus nerve may play a critical role in regulating HPA axis function via modulation of PVN CRF mRNA expression and putative PVN CRF neuronal activity. Furthermore, disruptions to vagal regulation of HPA axis function may increase alcohol intake and preference.
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Affiliation(s)
- Bailey N. Keller
- The Pennsylvania State University College of Medicine, Department of Neural and Behavioral Sciences
| | - Angela E. Snyder
- The Pennsylvania State University College of Medicine, Department of Neural and Behavioral Sciences
| | - Caitlin R. Coker
- The Pennsylvania State University College of Medicine, Department of Neural and Behavioral Sciences
| | - Elizabeth A. Aguilar
- The Pennsylvania State University College of Medicine, Department of Neural and Behavioral Sciences
| | - Mary K. O’Brien
- The Pennsylvania State University College of Medicine, Department of Neural and Behavioral Sciences
| | - Sarah S. Bingaman
- The Pennsylvania State University College of Medicine, Department of Neural and Behavioral Sciences
| | - Amy C. Arnold
- The Pennsylvania State University College of Medicine, Department of Neural and Behavioral Sciences
| | - Andras Hajnal
- The Pennsylvania State University College of Medicine, Department of Neural and Behavioral Sciences
| | - Yuval Silberman
- The Pennsylvania State University College of Medicine, Department of Neural and Behavioral Sciences
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Melendez-Araújo MS, do Carmo AS, Vieira FT, Lamarca F, Nakano EY, Lima RM, Dutra ES, de Carvalho KMB. Long-Term Lifestyle Habits and Quality of Life after Roux-in-Y Gastric Bypass in Brazilian Public versus Private Healthcare Systems: Beyond Weight Loss. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:6494. [PMID: 37569034 PMCID: PMC10419078 DOI: 10.3390/ijerph20156494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 07/26/2023] [Accepted: 07/28/2023] [Indexed: 08/13/2023]
Abstract
Lifestyle and health-related quality of life (HRQoL) are good markers of surgical obesity treatment. This study aimed to investigate the lifestyle and HRQoL of patients at least five years after Roux-en-Y gastric bypass in public (SUS) and private (PVT) Brazilian healthcare systems. In this cross-sectional study, weight loss (WL), % of excess WL (%EWL), diet quality, physical activity, alcohol consumption, and HRQoL were evaluated. Analysis of covariance, binary and multinomial logistic regression, adjusted for confounders, were performed. The SUS group had more vulnerable socioeconomic statuses than the PVT group. Total %WL and % EWL were 24.64 ± 0.99% and 60.46 ± 2.41%, respectively, without difference between groups. In the Pain/Discomfort and Anxiety/Depression domains of HRQoL, more than 50% reported moderate problems without differences between groups. Processed food ingestion was higher in the PVT (132.10 ± 60.15 g/1000 kcal) than in the SUS (103.43 ± 41.72 g/1000 kcal), however, without statistical significance (p = 0.093). The PVT group showed lower physical activity (OR: 0.23; 95%CI: 0.87-0.63; p = 0.004) and a higher risk of alcohol-related problems (OR: 3.23; 95%CI; 1.03-10.10; p = 0.044) compared to SUS group. Participants generally achieved satisfactory WL, regardless of healthcare systems. However, PVT participants had unfavorable lifestyle characteristics, highlighting the need for studies investigating environmental issues post-bariatric surgery.
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Affiliation(s)
- Mariana S. Melendez-Araújo
- Graduate Program of Human Nutrition, University of Brasília, Brasília 70910-900, Brazil; (M.S.M.-A.); (F.T.V.); (F.L.); (R.M.L.); (E.S.D.)
| | | | - Flávio Teixeira Vieira
- Graduate Program of Human Nutrition, University of Brasília, Brasília 70910-900, Brazil; (M.S.M.-A.); (F.T.V.); (F.L.); (R.M.L.); (E.S.D.)
| | - Fernando Lamarca
- Graduate Program of Human Nutrition, University of Brasília, Brasília 70910-900, Brazil; (M.S.M.-A.); (F.T.V.); (F.L.); (R.M.L.); (E.S.D.)
- Department of Applied Nutrition, Rio de Janeiro State University (UERJ), Rio de Janeiro 23900-000, Brazil
| | | | - Ricardo M. Lima
- Graduate Program of Human Nutrition, University of Brasília, Brasília 70910-900, Brazil; (M.S.M.-A.); (F.T.V.); (F.L.); (R.M.L.); (E.S.D.)
- Graduate Program in Physical Education, University of Brasilia, Brasília 70910-900, Brazil
| | - Eliane Said Dutra
- Graduate Program of Human Nutrition, University of Brasília, Brasília 70910-900, Brazil; (M.S.M.-A.); (F.T.V.); (F.L.); (R.M.L.); (E.S.D.)
| | - Kênia Mara Baiocchi de Carvalho
- Graduate Program of Human Nutrition, University of Brasília, Brasília 70910-900, Brazil; (M.S.M.-A.); (F.T.V.); (F.L.); (R.M.L.); (E.S.D.)
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Bariatric Surgery Is Associated with Alcohol-Related Liver Disease and Psychiatric Disorders Associated with AUD. Obes Surg 2023; 33:1494-1505. [PMID: 36881347 PMCID: PMC10156826 DOI: 10.1007/s11695-023-06490-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 01/22/2023] [Accepted: 01/30/2023] [Indexed: 03/08/2023]
Abstract
BACKGROUND/AIMS Bariatric surgery can increase the risk of addictive disorders and nutritional deficiencies. The aim of this study was to evaluate the association between bariatric surgery and alcohol use disorder (AUD), alcohol-related liver disease (ALD), and psychiatric disorders associated with AUD. The impact of vitamin D deficiency in these associations was also investigated. METHODS A cross-sectional study was performed using the National Inpatient Sample database and its ICD-9 codes information. Diagnostic and comorbidity data from hospital discharges were obtained from patients with bariatric surgery and other abdominal surgeries between 2005 and 2015. The two groups were then compared for alcohol-related outcomes after propensity-score matching. RESULTS The final study cohort included 537,757 patients with bariatric surgery and 537,757 with other abdominal surgeries. The bariatric surgery group had an increased risk of AUD [odds ratio (OR): 1.90; 95% CI: 1.85-1.95], ALD [OR: 1.29; 95% CI: 1.22-1.37], cirrhosis [OR, 1.39; 95% CI: 1.37-1.42], and psychiatric disorders associated with AUD [OR, 3.59; 95% CI: 3.37-3.84]. Vitamin D deficiency did not impact in the association between bariatric surgery and AUD, ALD, or psychiatric disorders associated with AUD. CONCLUSIONS Bariatric surgery is associated with an increased prevalence of AUD, ALD, and psychiatric disorders associated with AUD. These associations appear to be independent from vitamin D deficiency.
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10
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Andrade NL, Shenouda R, Sockalingam S, Fipps DC. Consultation-Liaison Case Conference: Psychiatric Care of Patients Who Undergo Bariatric Surgery. J Acad Consult Liaison Psychiatry 2023; 64:267-276. [PMID: 36764484 DOI: 10.1016/j.jaclp.2023.02.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 01/20/2023] [Accepted: 02/02/2023] [Indexed: 02/11/2023]
Abstract
We present the case of a 42-year-old female with major depressive disorder who received a Roux-en-Y gastric bypass and subsequently decompensated in her depression symptoms and began newly engaging in problematic alcohol use. Top experts in the consultation-liaison field, specifically bariatric surgery psychiatry, provide guidance for this commonly encountered clinical case based on their experience and a review of the available literature. Key teaching points include the presurgical psychosocial assessment, pertinent perioperative psychopharmacology, and problematic alcohol use after bariatric surgery.
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Affiliation(s)
| | - Raymone Shenouda
- Department of Psychiatry, Yale School of Medicine, New Haven, CT
| | | | - David C Fipps
- Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN.
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11
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Grigson PS, Hobkirk AL, Grigson PS, Hobkirk AL. Addiction III: From mouse to man. Brain Res Bull 2023; 193:22-26. [PMID: 36464128 DOI: 10.1016/j.brainresbull.2022.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022]
Affiliation(s)
- Patricia Sue Grigson
- Department of Neural and Behavioral Sciences, Penn State College of Medicine, USA.
| | - Andrea L Hobkirk
- Department of Psychiatry and Behavioral Health, Penn State College of Medicine, USA.
| | - Patricia Sue Grigson
- Department of Neural and Behavioral Sciences, Penn State College of Medicine, USA
| | - Andrea L Hobkirk
- Department of Psychiatry and Behavioral Health, Penn State College of Medicine, USA
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12
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Mercado A, Pham A, Wang Z, Huang W, Chan P, Ibrahim H, Gogineni H, Huang Y, Wang J. Effects of bariatric surgery on drug pharmacokinetics-Preclinical studies. Front Pharmacol 2023; 14:1133415. [PMID: 37089960 PMCID: PMC10113450 DOI: 10.3389/fphar.2023.1133415] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 03/27/2023] [Indexed: 04/25/2023] Open
Abstract
With the rising worldwide obesity rates, bariatric surgeries are increasing. Although the surgery offers an effective treatment option for weight loss, the procedure causes dramatic physiological and metabolic changes. Animal models in rodents provide a valuable tool for studying the systemic effects of the surgery. Since the surgery may significantly influence the pharmacokinetic properties of medications, animal studies should provide essential insight into mechanisms underlying changes in how the body handles the drug. This review summarizes research work in rodents regarding the impact of standard bariatric procedures on pharmacokinetics. A qualitative literature search was conducted via PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE. Studies that examined bariatric surgery's effects on drug pharmacokinetics in rodent models were included. Clinical studies and studies not involving drug interventions were excluded. A total of 15 studies were identified and assessed in this review. These studies demonstrate the possible impact of bariatric surgery on drug absorption, distribution, metabolism, excretion, and potential mechanisms. Pharmacokinetic changes exhibited in the limited pre-clinical studies highlight a need for further investigation to fully understand the impact and mechanism of bariatric surgery on drug responses.
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Affiliation(s)
- Angela Mercado
- College of Pharmacy, Western University of Health Sciences, Pomona, CA, United States
| | - Anna Pham
- College of Pharmacy, Western University of Health Sciences, Pomona, CA, United States
| | - Zhijun Wang
- College of Pharmacy, Marshall B. Ketchum University, Fullerton, CA, United States
| | - Wendong Huang
- Department of Diabetes Complications and Metabolism, Arthur Riggs-Diabetes and Metabolism Research Institute, City of Hope National Medical Center, Duarte, CA, United States
| | - Patrick Chan
- College of Pharmacy, Western University of Health Sciences, Pomona, CA, United States
| | | | - Hyma Gogineni
- College of Pharmacy, Western University of Health Sciences, Pomona, CA, United States
| | - Ying Huang
- College of Pharmacy, Western University of Health Sciences, Pomona, CA, United States
- *Correspondence: Ying Huang, ; Jeffrey Wang,
| | - Jeffrey Wang
- College of Pharmacy, Western University of Health Sciences, Pomona, CA, United States
- *Correspondence: Ying Huang, ; Jeffrey Wang,
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13
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Fipps DC, Sinha S, Diwan TS, Clark MM. Psychosocial considerations in the combined bariatric surgery and organ transplantation population: a review of the overlapping pathologies and outcomes. Curr Opin Organ Transplant 2022; 27:514-522. [PMID: 36103143 DOI: 10.1097/mot.0000000000001023] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
PURPOSE OF REVIEW This review highlights the salient data of the psychosocial concerns that influence outcomes of bariatric surgery and organ transplantation. RECENT FINDINGS Bariatric surgery has emerged as an important intervention with data supporting substantial and sustained weight loss, enhanced quality of life, remission of obesity-related medical comorbidities, and improved long-term patient and graft survival in transplant patients. Depression, suicide, anxiety, posttraumatic stress disorder, alcohol use, adherence, and psychopharmacology considerations can influence outcomes of both these surgeries. SUMMARY Obesity is increasingly prevalent among patients pursuing transplantation surgery, and it is often a factor in why a patient needs a transplant. However, obesity can be a barrier to receiving a transplant, with many centers implementing BMI criteria for surgery. Furthermore, obesity and obesity-related comorbidities after transplant can cause poor outcomes. In this context, many transplant centers have created programs that incorporate interventions (such as bariatric surgery) that target obesity in transplant candidates. A presurgery psychosocial assessment is an integral (and required) part of the process towards receiving a bariatric surgery and/or a transplantation surgery. When conducting a dual (bariatric and transplantation surgery) psychosocial assessment, it is prudent to understand the overlap and differentiation of specific psychosocial components that influence outcomes in these procedures.
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Affiliation(s)
| | - Shirshendu Sinha
- Department of Psychiatry and Psychology, Mayo Clinic, Scottsdale, Arizona, USA
| | | | - Matthew M Clark
- Department of Psychiatry and Psychology
- Division of Endocrinology, Diabetes, Metabolism and Nutrition, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
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14
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The Neural Code for Taste in the Nucleus of the Solitary Tract of Rats with Obesity Following Roux-En-Y Gastric Bypass Surgery. Nutrients 2022; 14:nu14194129. [PMID: 36235781 PMCID: PMC9570596 DOI: 10.3390/nu14194129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Revised: 09/26/2022] [Accepted: 09/29/2022] [Indexed: 11/07/2022] Open
Abstract
Previous work has shown that taste responses in the nucleus tractus solitarius (NTS; the first central relay for gustation) are blunted in rats with diet-induced obesity (DIO). Here, we studied whether these effects could be reversed by Roux-en-Y gastric bypass (RYGB) surgery, an effective treatment for obesity. Rats were fed a high energy diet (60% kcal fat; HED) both before and after undergoing RYGB. Electrophysiological responses from NTS cells in unrestrained rats were recorded as they licked tastants from a lick spout. Sweet, salty, and umami tastes, as well as their naturalistic counterparts, were presented. Results were compared with those of lean rats from a previous study. As with DIO rats, NTS cells in RYGB rats were more narrowly tuned, showed weaker responses, and less lick coherence than those in lean rats. Both DIO and RYGB rats licked at a slower rate than lean rats and paused more often during a lick bout. However, unlike DIO rats, the proportion of taste cells in RYGB rats was similar to that in lean rats. Our data show that, despite being maintained on a HED after surgery, RYGB can induce a partial recovery of the deficits seen in the NTS of DIO rats.
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15
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Keller BN, Hajnal A, Browning KN, Arnold AC, Silberman Y. Involvement of the Dorsal Vagal Complex in Alcohol-Related Behaviors. Front Behav Neurosci 2022; 16:801825. [PMID: 35330845 PMCID: PMC8940294 DOI: 10.3389/fnbeh.2022.801825] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 01/19/2022] [Indexed: 12/20/2022] Open
Abstract
The neurobiological mechanisms that regulate the development and maintenance of alcohol use disorder (AUD) are complex and involve a wide variety of within and between systems neuroadaptations. While classic reward, preoccupation, and withdrawal neurocircuits have been heavily studied in terms of AUD, viable treatment targets from this established literature have not proven clinically effective as of yet. Therefore, examination of additional neurocircuitries not classically studied in the context of AUD may provide novel therapeutic targets. Recent studies demonstrate that various neuropeptides systems are important modulators of alcohol reward, seeking, and intake behaviors. This includes neurocircuitry within the dorsal vagal complex (DVC), which is involved in the control of the autonomic nervous system, control of intake of natural rewards like food, and acts as a relay of interoceptive sensory information via interactions of numerous gut-brain peptides and neurotransmitter systems with DVC projections to central and peripheral targets. DVC neuron subtypes produce a variety of neuropeptides and transmitters and project to target brain regions critical for reward such as the mesolimbic dopamine system as well as other limbic areas important for the negative reinforcing and aversive properties of alcohol withdrawal such as the extended amygdala. This suggests the DVC may play a role in the modulation of various aspects of AUD. This review summarizes the current literature on neurotransmitters and neuropeptides systems in the DVC (e.g., norepinephrine, glucagon-like peptide 1, neurotensin, cholecystokinin, thyrotropin-releasing hormone), and their potential relevance to alcohol-related behaviors in humans and rodent models for AUD research. A better understanding of the role of the DVC in modulating alcohol related behaviors may lead to the elucidation of novel therapeutic targets for drug development in AUD.
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16
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Shevchouk OT, Tufvesson-Alm M, Jerlhag E. An Overview of Appetite-Regulatory Peptides in Addiction Processes; From Bench to Bed Side. Front Neurosci 2021; 15:774050. [PMID: 34955726 PMCID: PMC8695496 DOI: 10.3389/fnins.2021.774050] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Accepted: 11/08/2021] [Indexed: 12/17/2022] Open
Abstract
There is a substantial need for new pharmacological treatments of addiction, and appetite-regulatory peptides are implied as possible candidates. Appetite regulation is complex and involves anorexigenic hormones such as glucagon-like peptide-1 (GLP-1) and amylin, and orexigenic peptides like ghrelin and all are well-known for their effects on feeding behaviors. This overview will summarize more recent physiological aspects of these peptides, demonstrating that they modulate various aspects of addiction processes. Findings from preclinical, genetic, and experimental clinical studies exploring the association between appetite-regulatory peptides and the acute or chronic effects of addictive drugs will be introduced. Short or long-acting GLP-1 receptor agonists independently attenuate the acute rewarding properties of addictive drugs or reduce the chronic aspects of drugs. Genetic variation of the GLP-1 system is associated with alcohol use disorder. Also, the amylin pathway modulates the acute and chronic behavioral responses to addictive drugs. Ghrelin has been shown to activate reward-related behaviors. Moreover, ghrelin enhances, whereas pharmacological or genetic suppression of the ghrelin receptor attenuates the responses to various addictive drugs. Genetic studies and experimental clinical studies further support the associations between ghrelin and addiction processes. Further studies should explore the mechanisms modulating the ability of appetite-regulatory peptides to reduce addiction, and the effects of combination therapies or different diets on substance use are warranted. In summary, these studies provide evidence that appetite-regulatory peptides modulate reward and addiction processes, and deserve to be investigated as potential treatment target for addiction.
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Affiliation(s)
- Olesya T Shevchouk
- Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Maximilian Tufvesson-Alm
- Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Elisabet Jerlhag
- Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
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17
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Review of Changes in the Reinforcing Effects of Alcohol in Weight Loss Surgery Patients. Curr Psychiatry Rep 2021; 23:69. [PMID: 34613467 DOI: 10.1007/s11920-021-01281-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/22/2021] [Indexed: 12/22/2022]
Abstract
PURPOSE OF REVIEW The reinforcing effects of alcohol are well documented, and they have been shown to play a role in the development of alcohol use disorders (AUDs). Also well established is the fact that post-weight loss surgery (WLS) patients are at an increased risk for AUDs. In the current manuscript, we review the notion that the reinforcing effects of alcohol may change from before to after WLS and discuss a number of determinants of alcohol reinforcement change in WLS patients. RECENT FINDINGS It has been increasingly well understood that WLS patients are at an increased risk for AUD, but empirical support for the mechanisms that may cause this phenomenon have been lacking. Recently, a model was proposed that offered a number of different potentially causal variables as mechanisms that result in increased risk for AUD in these surgical patients. Change in the extent to which alcohol is reinforcing to WLS patients may be key in determining the likelihood of AUDs in this group. We review a host of biological, psychological, and social variables that ultimately impact how reinforcing alcohol is to WLS patients.
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18
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Brown RM, Guerrero-Hreins E, Brown WA, le Roux CW, Sumithran P. Potential gut-brain mechanisms behind adverse mental health outcomes of bariatric surgery. Nat Rev Endocrinol 2021; 17:549-559. [PMID: 34262156 DOI: 10.1038/s41574-021-00520-2] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/03/2021] [Indexed: 02/06/2023]
Abstract
Bariatric surgery induces sustained weight loss and metabolic benefits via notable effects on the gut-brain axis that lead to alterations in the neuroendocrine regulation of appetite and glycaemia. However, in a subset of patients, bariatric surgery is associated with adverse effects on mental health, including increased risk of suicide or self-harm as well as the emergence of depression and substance use disorders. The contributing factors behind these adverse effects are not well understood. Accumulating evidence indicates that there are important links between gut-derived hormones, microbial and bile acid profiles, and disorders of mood and substance use, which warrant further exploration in the context of changes in gut-brain signalling after bariatric surgery. Understanding the basis of these adverse effects is essential in order to optimize the health and well-being of people undergoing treatment for obesity.
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Affiliation(s)
- Robyn M Brown
- Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia
- Department of Biochemistry and Pharmacology, School of Biomedical Sciences, University of Melbourne, Parkville, Victoria, Australia
| | - Eva Guerrero-Hreins
- Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia
- Department of Biochemistry and Pharmacology, School of Biomedical Sciences, University of Melbourne, Parkville, Victoria, Australia
| | - Wendy A Brown
- Department of Surgery, Central Clinical School, Monash University, Alfred Hospital, Melbourne, Victoria, Australia
| | - Carel W le Roux
- Diabetes Complications Research Centre, Conway Institute, School of Medicine and Medical Sciences, University College, Dublin, Ireland
| | - Priya Sumithran
- Department of Medicine (St Vincent's), University of Melbourne, Melbourne, Victoria, Australia.
- Department of Endocrinology, Austin Health, Melbourne, Victoria, Australia.
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19
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Lefere S, Onghena L, Vanlander A, van Nieuwenhove Y, Devisscher L, Geerts A. Bariatric surgery and the liver-Mechanisms, benefits, and risks. Obes Rev 2021; 22:e13294. [PMID: 34002452 DOI: 10.1111/obr.13294] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 05/01/2021] [Accepted: 05/03/2021] [Indexed: 12/18/2022]
Abstract
The prevalence of obesity and metabolic diseases such as type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) has risen dramatically over the past decades. At present, bariatric surgery is the most effective treatment for this global health problem, through effects on food intake, gut hormone secretion, metabolic signaling pathways, and adipose tissue dysfunction. The liver occupies a central role in carbohydrate, protein, and lipid metabolism. Notably, a reduction in hepatic fat content and an improvement in hepatic insulin resistance are among the earliest beneficial effects of bariatric surgery, which has therefore emerged as an attractive treatment option for NAFLD. However, as the scope and popularity of weight loss surgery have expanded, new questions have arisen regarding its safety in patients with liver cirrhosis, the outcome of liver transplantation in patients with a history of bariatric surgery, and over incidental reports of liver failure following surgery. Studies in humans and rodents have also linked bariatric surgery to an increased risk of developing alcohol use disorder, a major risk factor for liver disease. This review integrates data from clinical and translational research to delineate both the beneficial impact of bariatric surgery on the liver and the potential risks involved.
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Affiliation(s)
- Sander Lefere
- Hepatology Research Unit, Department of Internal Medicine and Pediatrics, Liver Research Center Ghent, Ghent University, Ghent, Belgium.,Gut-Liver Immunopharmacology Unit, Department of Basic and Applied Medical Sciences, Liver Research Center Ghent, Ghent University, Ghent, Belgium
| | - Louis Onghena
- Department of Gastrointestinal Surgery, Ghent University, Ghent, Belgium.,Department of General and Hepatobiliary Surgery, Liver Transplantation Service, Ghent University, Ghent, Belgium
| | - Aude Vanlander
- Department of General and Hepatobiliary Surgery, Liver Transplantation Service, Ghent University, Ghent, Belgium
| | | | - Lindsey Devisscher
- Gut-Liver Immunopharmacology Unit, Department of Basic and Applied Medical Sciences, Liver Research Center Ghent, Ghent University, Ghent, Belgium
| | - Anja Geerts
- Hepatology Research Unit, Department of Internal Medicine and Pediatrics, Liver Research Center Ghent, Ghent University, Ghent, Belgium
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20
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Martin OA, Grant-Beurmann S, Orellana ER, Hajnal A, Fraser CM. Changes in the Gut Microbiota Following Bariatric Surgery Are Associated with Increased Alcohol Intake in a Female Rat Model. Alcohol Alcohol 2021; 56:605-613. [PMID: 34155502 DOI: 10.1093/alcalc/agab041] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 04/21/2021] [Accepted: 05/08/2021] [Indexed: 01/16/2023] Open
Abstract
AIMS We aimed to investigate if differences in gut microbiota diversity and composition are associated with post-operative alcohol intake following bariatric surgery in a rat model. METHODS Twenty-four female rats were randomized to three treatment groups: sham surgery, vertical sleeve gastrectomy (VSG) or Roux-en-Y gastric bypass (RYGB). Stool was collected pre- and post-operatively and 16S rRNA gene amplification and sequencing was performed. Analysis focused on correlating microbial diversity, type of surgery and alcohol (EtOH) intake. RESULTS Pre-operative stools samples on regular diet showed similar taxonomic composition and Shannon diversity among the three treatment groups. There was a significant decrease in Shannon diversity and a change in taxonomic composition of the gut microbiota after rats was fed high fat diet. Post-operatively, the RYGB group showed significantly lower taxonomic diversity than the VSG and sham groups, while the VSG and sham groups diversity were not significantly different. Taxonomic composition and function prediction based on PICRUSt analysis showed the RYGB group to be distinct from the VSG and sham groups. Shannon diversity was found to be negatively associated with EtOH intake. CONCLUSIONS Changes in the taxonomic profile of the gut microbiota following bariatric surgery, particularly RYGB, are associated with increased EtOH intake and may contribute to increased alcohol use disorder risk through the gut-brain-microbiome axis.
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Affiliation(s)
- Olivia A Martin
- Institute for Genome Sciences, University of Maryland School of Medicine, West Baltimore St. 21201, Baltimore, MD, USA.,Department of Surgery, University of Maryland School of Medicine, West Baltimore St. 21201, Baltimore, MD, USA
| | - Silvia Grant-Beurmann
- Institute for Genome Sciences, University of Maryland School of Medicine, West Baltimore St. 21201, Baltimore, MD, USA
| | - Elise R Orellana
- Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, University Drive. 10733, Hershey, PA, USA
| | - Andras Hajnal
- Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, University Drive. 10733, Hershey, PA, USA
| | - Claire M Fraser
- Institute for Genome Sciences, University of Maryland School of Medicine, West Baltimore St. 21201, Baltimore, MD, USA.,Department of Medicine, University of Maryland School of Medicine, West Baltimore St. 21201, Baltimore, MD, USA.,Department of Microbiology and Immunology, University of Maryland School of Medicine, West Baltimore St. 21201, Baltimore, MD, USA
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21
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Miller-Matero LR, Orlovskaia J, Hecht LM, Braciszeweski JM, Martens KM, Hamann A, Carlin AM. Hazardous Alcohol Use in the Four Years Following Bariatric Surgery. PSYCHOL HEALTH MED 2021; 27:1884-1890. [PMID: 34096405 DOI: 10.1080/13548506.2021.1930075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
The purpose of this study was to estimate the prevalence of hazardous drinking in the four years after bariatric surgery and investigate whether there are differences between those undergoing Roux-en-Y gastric bypass and sleeve gastrectomy. Participants (N = 564) who underwent bariatric surgery between 2014 and 2017 completed a survey regarding post-surgical alcohol use. The rate of alcohol use following bariatric surgery was significantly higher among those between 1- and 4-years post-surgery compared to those less than 1-year post-surgery. Of those who were consuming alcohol at the time of participation, 16.1% had scores indicative of hazardous drinking. The rate of hazardous drinking among those 3-4 years post-surgery was greater than those less than 1-year post-surgery with 33.3% of patients engaging in hazardous drinking at 3-4 years post-surgery. Patients undergoing sleeve gastrectomy had similar rates of hazardous drinking as RYGB (16.3% vs. 15.7%). Thus, findings showed that rates of hazardous drinking were higher among those further removed from bariatric surgery and patients undergoing sleeve gastrectomy appeared to have similar rates of hazardous drinking as those who underwent RYGB. Results suggest a need for monitoring of alcohol use for all patients pursuing bariatric surgery, regardless of surgery type.
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Affiliation(s)
- Lisa R Miller-Matero
- Henry Ford Health System, Behavioral Health, Detroit, MI USA.,Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI, USA
| | | | - Leah M Hecht
- Henry Ford Health System, Behavioral Health, Detroit, MI USA.,Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI, USA
| | - Jordan M Braciszeweski
- Henry Ford Health System, Behavioral Health, Detroit, MI USA.,Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI, USA
| | - Kellie M Martens
- Henry Ford Health System, Behavioral Health, Detroit, MI USA.,Department of General Surgery, Henry Ford Health System, Detroit, MI, USA
| | - Aaron Hamann
- Henry Ford Health System, Behavioral Health, Detroit, MI USA.,Department of General Surgery, Henry Ford Health System, Detroit, MI, USA
| | - Arthur M Carlin
- Department of General Surgery, Henry Ford Health System, Detroit, MI, USA
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22
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Bramming M, Becker U, Jørgensen MB, Neermark S, Bisgaard T, Tolstrup JS. Bariatric surgery and risk of alcohol use disorder: a register-based cohort study. Int J Epidemiol 2021; 49:1826-1835. [PMID: 33085738 DOI: 10.1093/ije/dyaa147] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/17/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Bariatric surgery has been associated with altered alcohol metabolism. We examined whether patients undergoing bariatric surgery have a higher risk of developing alcohol use disorder (AUD) compared with individuals with obesity who have not received bariatric surgery. METHODS In this prospective cohort study, we followed 13 430 patients undergoing bariatric surgery (95% gastric bypass) between 2005 and 2013 and a reference group of 21 021 individuals with obesity for a median of 6.9 years (5th-95th percentile: 4.0-9.8). Four different approaches were used to account for baseline differences between the two groups: (i) adjustment; (ii) inverse probability of treatment weighting (IPTW); (iii) 1:1 matching based on propensity scores; and (iv) before-and-after analysis comparing the bariatric surgery group with itself 5 years before and after surgery. Cox proportional hazard modelling was used to estimate hazard ratios of AUD defined from national registers. RESULTS When applying the IPTW approach, the hazard ratio (HR) of AUD for bariatric surgery patients was 7.29 [95% confidence interval (CI): 5.06-9.48] compared with individuals without surgery. When employing different approaches (adjustment for baseline variables, matching on propensity scores, before-and-after analyses), results were of similar magnitude. Analysis stratified by time after surgery revealed a higher risk of AUD already within the first year following surgery [HR: 2.77 (95% CI: 1.39-5.53)]. CONCLUSIONS Patients undergoing bariatric surgery have a higher risk of developing AUD compared with individuals without bariatric surgery. The higher risk observed in this group of patients cannot be explained by differences in baseline characteristics such as socioeconomic factors. Despite the higher risk of AUD, only few individuals developed AUD. Individuals with disabling obesity should therefore not rule out surgery based on these results but rather be aware of negative implications.
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Affiliation(s)
- Maja Bramming
- National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark
| | - Ulrik Becker
- National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark.,Gastrounit Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Maja B Jørgensen
- National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark
| | - Søren Neermark
- Gastrounit Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.,Center of Planning, Danish Board of Health, Copenhagen, Denmark
| | - Thue Bisgaard
- Surgical Department, Zealand University Hospital, Køge, Denmark
| | - Janne S Tolstrup
- National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark
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23
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Bhavsar-Burke I, Jansson-Knodell CL, Gilmore AC, Crabb DW. Review article: the role of nutrition in alcohol-associated liver disease. Aliment Pharmacol Ther 2021; 53:1268-1276. [PMID: 33896017 DOI: 10.1111/apt.16380] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 02/05/2021] [Accepted: 04/07/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Malnutrition is a commonly encountered issue in patients with alcohol-associated liver disease. The role of nutritional supplementation in the management of alcohol-associated liver disease is integral to patient outcomes-it has been shown to decrease rates of hepatic encephalopathy, improve outcomes post-liver transplant, reduce 90-day hospital readmissions and lower mortality. Despite these benefits, many studies have shown nutritional support to be an underutilised tool in the care of patients with alcohol-associated liver disease. AIMS To review the epidemiology, pathophysiology, recommendations for nutritional assessment and supplementation, as well as future directions for research of the relationship between nutrition and alcohol-associated liver disease. METHODS A literature search was conducted via PubMed using MeSH terms to inform this narrative review. RESULTS Decreased dietary intake, socioeconomic status, impaired absorption of nutrients and increased free radical species are implicated in the pathophysiology of malnutrition in alcohol-associated liver disease. CONCLUSIONS Malnutrition is common in alcohol-associated liver disease, and physicians should be aware of its association with poor clinical outcomes. Routine nutritional assessment, involvement of a dietician and nutritional supplementation are recommended to improve clinical outcomes in patients with alcohol-associated liver disease.
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Affiliation(s)
- Indira Bhavsar-Burke
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University, Indianapolis, IN, USA
| | - Claire L Jansson-Knodell
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University, Indianapolis, IN, USA
| | - Ashley C Gilmore
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University, Indianapolis, IN, USA
| | - David W Crabb
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University, Indianapolis, IN, USA
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24
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Agarwal K, Manza P, Leggio L, Livinski AA, Volkow ND, Joseph PV. Sensory cue reactivity: Sensitization in alcohol use disorder and obesity. Neurosci Biobehav Rev 2021; 124:326-357. [PMID: 33587959 DOI: 10.1016/j.neubiorev.2021.02.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 02/03/2021] [Accepted: 02/07/2021] [Indexed: 12/21/2022]
Abstract
Neuroimaging techniques to measure the function of the human brain such as electroencephalography (EEG), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI), are powerful tools for understanding the underlying neural circuitry associated with alcohol use disorder (AUD) and obesity. The sensory (visual, taste and smell) paradigms used in neuroimaging studies represent an ideal platform to investigate the connection between the different neural circuits subserving the reward/executive control systems in these disorders, which may offer a translational mechanism for novel intervention predictions. Thus, the current review provides an integrated summary of the recent neuroimaging studies that have applied cue-reactivity paradigms and neuromodulation strategies to explore underlying alterations in neural circuitry as well in treatment strategies in AUD and obesity. Finally, we discuss literature on mechanisms associated with increased alcohol sensitivity post-bariatric surgery (BS) which offers guidance for future research to use sensory percepts in elucidating the relation of reward signaling in AUD development post-BS.
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Affiliation(s)
- Khushbu Agarwal
- National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA; National Institute of Nursing Research, Bethesda, MD, USA
| | - Peter Manza
- National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA
| | - Lorenzo Leggio
- National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA; National Institute on Drug Abuse, Bethesda and Baltimore, MD, USA
| | | | - Nora D Volkow
- National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA; National Institute on Drug Abuse, Bethesda and Baltimore, MD, USA
| | - Paule Valery Joseph
- National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA; National Institute of Nursing Research, Bethesda, MD, USA.
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25
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Albaugh VL, Kindel TL, Nissen SE, Aminian A. Cardiovascular Risk Reduction Following Metabolic and Bariatric Surgery. Surg Clin North Am 2021; 101:269-294. [PMID: 33743969 DOI: 10.1016/j.suc.2020.12.012] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality in developed countries, with worsening pandemics of type 2 diabetes mellitus and obesity as major cardiovascular (CV) risk factors. Clinical trials of nonsurgical obesity treatments have not shown benefits in CVD, although recent diabetes trials have demonstrated major CV benefits. In many retrospective and prospective cohort studies, however, metabolic (bariatric) surgery is associated with substantial and reproducible CVD benefits. Despite a lack of prospective, randomized clinical trials, data suggest metabolic surgery may be the most effective modality for CVD risk reduction, likely through weight loss and weight loss-independent mechanisms.
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Affiliation(s)
- Vance L Albaugh
- Department of General Surgery, Bariatric and Metabolic Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Tammy L Kindel
- Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Steven E Nissen
- Department of Cardiovascular Medicine, Heart & Vascular Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Ali Aminian
- Department of General Surgery, Bariatric and Metabolic Institute, Cleveland Clinic, 9500 Euclid Avenue, M61, Cleveland, OH 44195, USA.
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26
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Orellana ER, Nyland JE, Horvath N, Hajnal A. Vagotomy increases alcohol intake in female rats in diet dependent manner: Implications for increased alcohol use disorder after roux-en-y gastric bypass surgery. Physiol Behav 2021; 235:113309. [PMID: 33412192 DOI: 10.1016/j.physbeh.2021.113309] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Revised: 12/18/2020] [Accepted: 12/31/2020] [Indexed: 12/25/2022]
Abstract
A variety of weight loss surgeries have been developed to fight the obesity epidemic, with Roux-en-Y gastric bypass (RYGB) being one of the most effective and popular procedures. However, the underlying mechanisms behind its efficacy are still not well understood. Furthermore, growing clinical evidence suggests that RYGB may result in increased risk for development of alcohol use disorder (AUD). The vagus nerve is a potentially critical contributor to increased risk of AUD following RYGB due to the potential for significant damage to the vagus during surgery, which has been confirmed in rodent studies. Studies aiming at the mechanisms underlying development of alcohol or substance use disorders following the surgery have exclusively used male rats, despite the majority of RYGB patients being female. Thus, the current study had two objectives: 1) to investigate the effect of RYGB on ethanol (EtOH) intake in female rats using a protocol previously established in male rats, and 2) to test the effect of vagal damage and high fat diet (HFD) on EtOH intake in female rats. In the first study, 22 female rats were maintained on HFD for four weeks and then split into two surgical groups, RYGB (n = 10) and Sham (n = 12). All rats then underwent a two-bottle choice test of increasing EtOH concentrations: 2%, 4%, 6%, 8%. Rats were then forced to abstain from EtOH for two weeks, after which access to 8% EtOH was reinstated. The RYGB female rats significantly increased their intake for low concentrations of EtOH (2% and 4%) and during the reinstatement period for 8%. These results mirror those seen in male rats, and thus, confirms RYGB in female rats as an equally viable model to males. In the second study, 40 female rats were separated into four groups: HFD/Sham, HFD/Vagotomy, normal diet (ND)/Sham, and ND/Vagotomy. All rats then were subjected to the same two-bottle choice test protocol as in the previous study. Rats in the vagotomy condition had significantly greater preference for 2% and 4% EtOH compared with Sham-operated controls. EtOH intake, either in ml or adjusted for body weight, was greater in rats maintained on ND compared with rats maintained on HFD. These data suggest that vagal damage may, at least in part, contribute to increased preference for EtOH. Furthermore, this increase in EtOH preference is counter to the blunting effect of HFD. In conclusion, the data presented here suggest a role for vagal damage in risk of AUD after weight loss surgery.
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Affiliation(s)
- Elise R Orellana
- The Pennsylvania State University College of Medicine, Department of Neural and Behavioral Sciences, United States.
| | - Jennifer E Nyland
- The Pennsylvania State University College of Medicine, Department of Neural and Behavioral Sciences, United States
| | - Nelli Horvath
- The Pennsylvania State University College of Medicine, Department of Neural and Behavioral Sciences, United States
| | - Andras Hajnal
- The Pennsylvania State University College of Medicine, Department of Neural and Behavioral Sciences, United States
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27
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McGregor M, Hamilton J, Hajnal A, Thanos PK. Roux-en-Y gastric bypass increases GABA-A receptor levels in regions of the rat brain involved in object recognition memory and perceptual acuity. Physiol Behav 2020; 224:113053. [PMID: 32645414 DOI: 10.1016/j.physbeh.2020.113053] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 06/15/2020] [Accepted: 07/04/2020] [Indexed: 01/09/2023]
Abstract
Roux-en-Y gastric bypass surgery (RYGB), one of the most common and successful procedures for combatting obesity, is associated with post-surgery substance use disorder (SUD) and other addictive behaviors in a subset of patients. We investigated the effects of RYGB on GABA-A receptor levels in the rat brain to identify potential mechanisms of this behavior. The GABAergic system is affected in addiction and has been implicated in the pathology of obesity. We assigned male Sprague-Dawley rats to four groups: standard, low fat diet with sham surgery (control), ad libitum HFD with sham surgery (Sham), calorie restricted HFD with sham surgery (Sham-FR), or HFD with RYGB surgery. Surgery was performed after 8 weeks on the control or HFD diet. Rats maintained their respective diets for 9 weeks post-surgery, then were sacrificed for GABA-A receptor autoradiography using the [3H] Flunitrazepam ligand. We identified increased GABA-A binding in the perirhinal cortex of ad-libitum HFD fed rats compared to normal diet controls. RYGB surgery increased GABA-A in the ectorhinal cortex compared to normal diet controls, and increased binding in the jaw region of the primary somatosensory cortex compared to food-restricted rats that received sham surgery. Hypothalamus GABA-A was also negatively correlated with body weight in the RYGB group, where GABA signaling may play a role in obesity regulation. These results suggest that HFD and RYGB modulate GABA signaling in regions important for object recognition memory, and that increased GABA-A levels in the jaw's perceptual field cortex arise from the surgery itself, independent of caloric restriction.
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Affiliation(s)
- Matthew McGregor
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, NY, USA
| | - John Hamilton
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, NY, USA; Department of Psychology, State University of New York at Buffalo, Buffalo, NY, USA
| | - Andras Hajnal
- Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, PA, USA
| | - Panayotis K Thanos
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, NY, USA; Department of Psychology, State University of New York at Buffalo, Buffalo, NY, USA.
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28
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Tuero C, Valenti V, Rotellar F, Landecho MF, Cienfuegos JA, Frühbeck G. Revisiting the Ghrelin Changes Following Bariatric and Metabolic Surgery. Obes Surg 2020; 30:2763-2780. [PMID: 32323063 DOI: 10.1007/s11695-020-04601-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Since the description of ghrelin in 1999, several studies have dug into the effects of this hormone and its relationship with bariatric surgery. While some aspects are still unresolved, a clear connection between ghrelin and the changes after metabolic surgery have been established. Besides weight loss, a significant amelioration in obesity-related comorbidities following surgery has also been reported. These changes in patients occur in the early postoperative period, before the weight loss appears, so that amelioration may be mainly due to hormonal changes. The purpose of this review is to go through the current body of knowledge of ghrelin's physiology, as well as to update and clarify the changes that take place in ghrelin concentrations following bariatric/metabolic surgery together with their potential consolidation to outcomes.
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Affiliation(s)
- Carlota Tuero
- Obesity Area, Clínica Universidad de Navarra, Avenida Pio XII 36, 31008, Pamplona, Navarra, Spain.
- Department of Surgery, Clínica Universidad de Navarra, Pamplona, Spain.
| | - Victor Valenti
- Obesity Area, Clínica Universidad de Navarra, Avenida Pio XII 36, 31008, Pamplona, Navarra, Spain
- Department of Surgery, Clínica Universidad de Navarra, Pamplona, Spain
- CIBEROBN, Instituto de Salud Carlos III, Pamplona, Navarra, Spain
- Obesity and Adipobiology Group, IdiSNA, Pamplona, Spain
| | - Fernando Rotellar
- Obesity Area, Clínica Universidad de Navarra, Avenida Pio XII 36, 31008, Pamplona, Navarra, Spain
- Department of Surgery, Clínica Universidad de Navarra, Pamplona, Spain
- CIBEROBN, Instituto de Salud Carlos III, Pamplona, Navarra, Spain
- Obesity and Adipobiology Group, IdiSNA, Pamplona, Spain
| | - Manuel F Landecho
- Obesity Area, Clínica Universidad de Navarra, Avenida Pio XII 36, 31008, Pamplona, Navarra, Spain
- Department of Internal Medicine, General Health Check-up unit, Clínica Universidad de Navarra, Pamplona, Spain
| | - Javier A Cienfuegos
- Obesity Area, Clínica Universidad de Navarra, Avenida Pio XII 36, 31008, Pamplona, Navarra, Spain
- Department of Surgery, Clínica Universidad de Navarra, Pamplona, Spain
- CIBEROBN, Instituto de Salud Carlos III, Pamplona, Navarra, Spain
- Obesity and Adipobiology Group, IdiSNA, Pamplona, Spain
| | - Gema Frühbeck
- Obesity Area, Clínica Universidad de Navarra, Avenida Pio XII 36, 31008, Pamplona, Navarra, Spain.
- CIBEROBN, Instituto de Salud Carlos III, Pamplona, Navarra, Spain.
- Obesity and Adipobiology Group, IdiSNA, Pamplona, Spain.
- Department of Endocrinology and Nutrition, Clínica Universidad de Navarra, Pamplona, Spain.
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29
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Kunos G. Interactions Between Alcohol and the Endocannabinoid System. Alcohol Clin Exp Res 2020; 44:790-805. [PMID: 32056226 DOI: 10.1111/acer.14306] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Accepted: 02/05/2020] [Indexed: 12/12/2022]
Abstract
Endocannabinoids are lipid mediators that interact with the same cannabinoid receptors that recognize Δ9 -tetrahydrocannabinol (THC), the psychoactive constituent of marijuana, to induce similar effects in the brain and periphery. Alcohol and THC are both addictive substances whose acute use elicits rewarding effects that can lead to chronic and compulsive use via engaging similar signaling pathways in the brain. In the liver, both alcohol and endocannabinoids activate lipogenic gene expression leading to fatty liver disease. This review focuses on evidence accumulated over the last 2 decades to indicate that both the addictive neural effects of ethanol and its organ toxic effects in the liver and elsewhere are mediated, to a large extent, by endocannabinoids signaling via cannabinoid-1 receptors (CB1 R). The therapeutic potential of CB1 R blockade globally or in peripheral tissues only is also discussed.
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Affiliation(s)
- George Kunos
- From the, Division of Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland
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30
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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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31
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Smith NK, Hackett TA, Galli A, Flynn CR. GLP-1: Molecular mechanisms and outcomes of a complex signaling system. Neurochem Int 2019; 128:94-105. [PMID: 31002893 PMCID: PMC7081944 DOI: 10.1016/j.neuint.2019.04.010] [Citation(s) in RCA: 91] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Revised: 03/26/2019] [Accepted: 04/15/2019] [Indexed: 12/15/2022]
Abstract
Meal ingestion provokes the release of hormones and transmitters, which in turn regulate energy homeostasis and feeding behavior. One such hormone, glucagon-like peptide-1 (GLP-1), has received significant attention in the treatment of obesity and diabetes due to its potent incretin effect. In addition to the peripheral actions of GLP-1, this hormone is able to alter behavior through the modulation of multiple neural circuits. Recent work that focused on elucidating the mechanisms and outcomes of GLP-1 neuromodulation led to the discovery of an impressive array of GLP-1 actions. Here, we summarize the many levels at which the GLP-1 signal adapts to different systems, with the goal being to provide a background against which to guide future research.
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Affiliation(s)
- Nicholas K Smith
- Vanderbilt Brain Institute, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Troy A Hackett
- Department of Hearing and Speech Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Aurelio Galli
- Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
| | - Charles R Flynn
- Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
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32
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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: 33] [Impact Index Per Article: 5.5] [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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33
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Ivezaj V, Benoit SC, Davis J, Engel S, Lloret-Linares C, Mitchell JE, Pepino MY, Rogers AM, Steffen K, Sogg S. Changes in Alcohol Use after Metabolic and Bariatric Surgery: Predictors and Mechanisms. Curr Psychiatry Rep 2019; 21:85. [PMID: 31410716 PMCID: PMC7057935 DOI: 10.1007/s11920-019-1070-8] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
PURPOSE OF REVIEW This review synthesized the literature on predictors and mechanisms of post-bariatric alcohol problems, in order to guide future research on prevention and treatment targets. RECENT FINDINGS Consistent evidence suggests an elevated risk of developing problems with alcohol following bariatric surgery. While there is a paucity of empirical data on predictors of problematic alcohol use after bariatric surgery, being male, a younger age, smoking, regular alcohol consumption, pre-surgical alcohol use disorder, and a lower sense of belonging have predicted alcohol misuse post-operatively. This review synthesizes potential mechanisms including specific bariatric surgical procedures, peptides and reinforcement/reward pathways, pharmacokinetics, and genetic influences. Finally, potential misperceptions regarding mechanisms are explored. Certain bariatric procedures elevate the risk of alcohol misuse post-operatively. Future research should serve to elucidate the complexities of reward signaling, genetically mediated mechanisms, and pharmacokinetics in relation to alcohol use across gender and developmental period by surgery type.
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Affiliation(s)
- Valentina Ivezaj
- Yale School of Medicine, 301 Cedar Street, 2nd Floor, New Haven, CT, 06519, USA.
| | | | - Jon Davis
- Washington State University, Pullman, WA, 99164, USA
| | | | - Celia Lloret-Linares
- Maladies Nutritionnelles et métaboliques, Ramsay-Générale de Santé, Hôpital Privé Pays de Savoie, 74105, Annemasse, France
| | - James E Mitchell
- University of North Dakota School of Medicine and Health Sciences, Fargo, ND, 58202, USA
| | - M Yanina Pepino
- University of Illinois at Urbana Champaign, Urbana, IL, 61801, USA
| | - Ann M Rogers
- Penn State Health Milton S Hershey Medical Center, Hershey, PA, 17033, USA
| | | | - Stephanie Sogg
- Massachusetts General Hospital Weight Center, Boston, MA, 02114, USA
- Harvard Medical School, Boston, MA, 02115, USA
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34
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Suter PM, Perger L. [Alcohol and the Bariatric Patient: When One Drink Becomes Two Drinks]. PRAXIS 2019; 108:655-662. [PMID: 31387501 DOI: 10.1024/1661-8157/a003280] [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: 06/10/2023]
Abstract
Alcohol and the Bariatric Patient: When One Drink Becomes Two Drinks Abstract. Moderate consumption of alcohol is a risk factor for weight gain and obesity. Alcohol affects all components of the energy balance. Alcohol consumption is - as in the general population - also a widespread phenomenon in obese and bariatric patients. As a function of the bariatric surgery technique, alcohol metabolism is altered: gastric bypass surgery and sleeve gastrectomy lead to a faster absorption of alcohol, higher peak alcohol concentration and a longer alcohol persistence in the circulation. Further reward mechanisms for alcohol are changed, so that alcohol consumption is enhanced and promoted, with an increased risk to develop alcohol dependency. It is time to address these issues in the daily practice and to fill the existing research gaps.
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Affiliation(s)
- Paolo M Suter
- 1 Klinik und Poliklinik für Innere Medizin, Universitätsspital Zürich
| | - Ludwig Perger
- 1 Klinik und Poliklinik für Innere Medizin, Universitätsspital Zürich
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35
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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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36
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Godlewski G, Cinar R, Coffey NJ, Liu J, Jourdan T, Mukhopadhyay B, Chedester L, Liu Z, Osei-Hyiaman D, Iyer MR, Park JK, Smith RG, Iwakura H, Kunos G. Targeting Peripheral CB 1 Receptors Reduces Ethanol Intake via a Gut-Brain Axis. Cell Metab 2019; 29:1320-1333.e8. [PMID: 31105045 PMCID: PMC6551287 DOI: 10.1016/j.cmet.2019.04.012] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2018] [Revised: 03/01/2019] [Accepted: 04/21/2019] [Indexed: 12/21/2022]
Abstract
Endocannabinoids acting on the cannabinoid-1 receptor (CB1R) or ghrelin acting on its receptor (GHS-R1A) both promote alcohol-seeking behavior, but an interaction between the two signaling systems has not been explored. Here, we report that the peripheral CB1R inverse agonist JD5037 reduces ethanol drinking in wild-type mice but not in mice lacking CB1R, ghrelin peptide or GHS-R1A. JD5037 treatment of alcohol-drinking mice inhibits the formation of biologically active octanoyl-ghrelin without affecting its inactive precursor desacyl-ghrelin. In ghrelin-producing stomach cells, JD5037 reduced the level of the substrate octanoyl-carnitine generated from palmitoyl-carnitine by increasing fatty acid β-oxidation. Blocking gastric vagal afferents abrogated the ability of either CB1R or GHS-R1A blockade to reduce ethanol drinking. We conclude that blocking CB1R in ghrelin-producing cells reduces alcohol drinking by inhibiting the formation of active ghrelin and its signaling via gastric vagal afferents. Thus, peripheral CB1R blockade may have therapeutic potential in the treatment of alcoholism.
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Affiliation(s)
- Grzegorz Godlewski
- Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA.
| | - Resat Cinar
- Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
| | - Nathan J Coffey
- Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
| | - Jie Liu
- Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
| | - Tony Jourdan
- Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
| | - Bani Mukhopadhyay
- Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
| | - Lee Chedester
- Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
| | - Ziyi Liu
- Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
| | - Douglas Osei-Hyiaman
- Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
| | - Malliga R Iyer
- Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
| | - Joshua K Park
- Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
| | - Roy G Smith
- Scripps Research Institute, Jupiter, FL 33458, USA
| | - Hiroshi Iwakura
- Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Japan
| | - George Kunos
- Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA.
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Neuro-hormonal mechanisms underlying changes in reward related behaviors following weight loss surgery: Potential pharmacological targets. Biochem Pharmacol 2019; 164:106-114. [PMID: 30954487 DOI: 10.1016/j.bcp.2019.04.004] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Accepted: 04/03/2019] [Indexed: 12/11/2022]
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Farokhnia M, Faulkner ML, Piacentino D, Lee MR, Leggio L. Ghrelin: From a gut hormone to a potential therapeutic target for alcohol use disorder. Physiol Behav 2019; 204:49-57. [DOI: 10.1016/j.physbeh.2019.02.008] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Revised: 01/24/2019] [Accepted: 02/06/2019] [Indexed: 12/22/2022]
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Sirohi S, Skripnikova E, Davis JF. Vertical Sleeve Gastrectomy Attenuates Hedonic Feeding Without Impacting Alcohol Drinking in Rats. Obesity (Silver Spring) 2019; 27:603-611. [PMID: 30740914 PMCID: PMC6430654 DOI: 10.1002/oby.22415] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2018] [Accepted: 11/13/2018] [Indexed: 12/22/2022]
Abstract
OBJECTIVE Roux-en-Y gastric bypass surgery and vertical sleeve gastrectomy (VSG) are the most commonly performed bariatric procedures. Whereas studies report new-onset alcohol misuse following Roux-en-Y gastric bypass, the impact of VSG on alcohol intake is less clear. Hedonic feeding, alcohol drinking, and hypothalamic obesity-related gene expression following VSG were evaluated. METHODS Male Long-Evans rats underwent VSG or sham surgery. To evaluate hedonic feeding, rats received a high-fat diet following behavioral satiation on chow. Alcohol (5%-10% v/v) drinking was assessed in a two-bottle choice paradigm. Finally, polymerase chain reaction array evaluated gene expression. RESULTS VSG induced moderate but significant weight loss. Sham rats significantly escalated high-fat diet intake following behavioral satiation, an effect significantly reduced in VSG rats. A moderate decrease in alcohol intake was observed in VSG rats at low (5%) alcohol concentration. However, overall, no significant between-group differences were evident. Key hypothalamic orexigenic transcripts linked to stimulation of food and alcohol intake were significantly decreased in VSG rats. CONCLUSIONS VSG attenuated hedonic feeding without impacting alcohol drinking, an effect potentially mediated by alterations in genetic information flow within the hypothalamus. Importantly, these data highlight VSG as an effective bariatric procedure with a potentially reduced risk of developing alcohol use disorder.
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Affiliation(s)
- Sunil Sirohi
- Laboratory of Endocrine and Neuropsychiatric Disorders, Division of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, LA
- Corresponding Authors: Jon F. Davis, PhD, Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, 1815 Ferdinand’s Lane, Pullman, WA, 99164, Tel (Office): 509-335-8163, , Sunil Sirohi, PhD, Laboratory of Endocrine and Neuropsychiatric Disorders, Division of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, 1 Drexel Dr., New Orleans, LA 70125, Tel (Office): 504-520-5471; (lab) 504-520-5332, ;
| | - Elena Skripnikova
- Laboratory of Endocrine and Neuropsychiatric Disorders, Division of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, LA
| | - Jon F. Davis
- Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA
- Corresponding Authors: Jon F. Davis, PhD, Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, 1815 Ferdinand’s Lane, Pullman, WA, 99164, Tel (Office): 509-335-8163, , Sunil Sirohi, PhD, Laboratory of Endocrine and Neuropsychiatric Disorders, Division of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, 1 Drexel Dr., New Orleans, LA 70125, Tel (Office): 504-520-5471; (lab) 504-520-5332, ;
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40
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Jerlhag E. Gut-brain axis and addictive disorders: A review with focus on alcohol and drugs of abuse. Pharmacol Ther 2018; 196:1-14. [PMID: 30439457 DOI: 10.1016/j.pharmthera.2018.11.005] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Due to the limited efficacy of existing medications for addictive disorders including alcohol use disorder (AUD), the need for additional medications is substantial. Potential new medications for addiction can be identified through investigation of the neurochemical substrates mediating the ability of drugs of abuse such as alcohol to activate the mesolimbic dopamine system. Interestingly, recent studies implicate neuropeptides of the gut-brain axis as modulators of reward and addiction processes. The present review therefore summarizes the current studies investigating the ability of the gut-brain peptides ghrelin, glucagon-like peptide-1 (GLP-1), amylin and neuromedin U (NMU) to modulate alcohol- and drug-related behaviors in rodents and humans. Extensive literature demonstrates that ghrelin, the only known orexigenic neuropeptide to date, enhances reward as well as the intake of alcohol, and other drugs of abuse, while ghrelin receptor antagonism has the opposite effects. On the other hand, the anorexigenic peptides GLP-1, amylin and NMU independently inhibits reward from alcohol and drugs of abuse in rodents. Collectively, these rodent and human studies imply that central ghrelin, GLP-1, amylin and NMU signaling may contribute to addiction processes. Therefore, the need for randomized clinical trials investigating the effects of agents targeting these aforementioned systems on drug/alcohol use is substantial.
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Affiliation(s)
- Elisabet Jerlhag
- Institute of Neuroscience and Physiology, Department of Pharmacology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
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41
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New onset alcohol use disorder following bariatric surgery. Surg Endosc 2018; 33:2521-2530. [DOI: 10.1007/s00464-018-6545-x] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Accepted: 10/15/2018] [Indexed: 12/16/2022]
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Farokhnia M, Lee MR, Farinelli LA, Ramchandani VA, Akhlaghi F, Leggio L. Pharmacological manipulation of the ghrelin system and alcohol hangover symptoms in heavy drinking individuals: Is there a link? Pharmacol Biochem Behav 2018; 172:39-49. [PMID: 30030128 DOI: 10.1016/j.pbb.2018.07.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Revised: 06/23/2018] [Accepted: 07/16/2018] [Indexed: 12/14/2022]
Abstract
Ghrelin, an orexigenic peptide synthesized in the stomach, is a key player in the gut-brain axis. In addition to its role in regulating food intake and energy homeostasis, ghrelin has been shown to modulate alcohol-related behaviors. Alcohol consumption frequently results in hangover, an underexplored phenomenon with considerable medical, psychological, and socioeconomic consequences. While the pathophysiology of hangover is not clear, contributions of mechanisms such as alcohol-induced metabolic/endocrine changes, inflammatory/immune response, oxidative stress, and gut dysbiosis have been reported. Interestingly, these mechanisms considerably overlap with ghrelin's physiological functions. Here, we investigated whether pharmacological manipulation of the ghrelin system may affect alcohol hangover symptoms. Data were obtained from two placebo-controlled laboratory studies. The first study tested the effects of intravenous (IV) ghrelin and consisted of two experiments: a progressive-ratio IV alcohol self-administration (IV-ASA) and a fixed-dose IV alcohol clamp. The second study tested the effects of an oral ghrelin receptor inverse agonist (PF-5190457) and included a fixed-dose oral alcohol administration experiment. Alcohol hangover data were collected the morning after each alcohol administration experiment using the Acute Hangover Scale (AHS). IV ghrelin, compared to placebo, significantly reduced alcohol hangover after IV-ASA (p = 0.04) and alcohol clamp (p = 0.04); PF-5190457 had no significant effect on AHS scores. Females reported significantly higher hangover symptoms than males following the IV-ASA experiment (p = 0.04), but no gender × drug condition (ghrelin vs. placebo) effect was found. AHS total scores were positively correlated with peak subjective responses, including 'stimulation' (p = 0.08), 'sedation' (p = 0.009), 'feel high' (p = 0.05), and 'feel intoxicated' (p = 0.03) during the IV-ASA. IV ghrelin blunted the positive association between alcohol sedation and hangover as shown by trend-level drug × sedation effect (p = 0.08). This is the first study showing that exogenous ghrelin administration, but not ghrelin receptor inverse agonism, affects hangover symptoms. Future research should investigate the potential mechanism(s) underlying this effect.
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Affiliation(s)
- Mehdi Farokhnia
- Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA
| | - Mary R Lee
- Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA
| | - Lisa A Farinelli
- Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA
| | - Vijay A Ramchandani
- Section on Human Psychopharmacology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA
| | - Fatemeh Akhlaghi
- Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, USA
| | - Lorenzo Leggio
- Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA; Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence, RI, USA.
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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: 17] [Impact Index Per Article: 2.4] [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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Abstract
Obesity prevalence continues to increase worldwide, as do the numerous chronic diseases associated with obesity, including diabetes, non-alcoholic fatty liver disease, dyslipidemia, and hypertension. The prevalence of bariatric surgery also continues to increase and remains the most effective and sustainable treatment for obesity. Over the last several years, numerous prospective and longitudinal studies have demonstrated the benefits of bariatric surgery on weight loss, mortality, and other chronic diseases. Even though the mechanisms underlying many of these beneficial effects remain poorly understood, surgical management of obesity continues to increase given its unmatched efficacy. In this commentary, we discuss recent clinical advancements as well as several areas needed for future research, including indications for bariatric and metabolic surgery, determination of responders and non-responders, metabolic surgery in non-obese individuals, and the evolving role of bariatric surgery in adolescents.
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Affiliation(s)
- Vance L Albaugh
- Department of Surgery, MCN CC-2308, Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Naji N Abumrad
- Department of Surgery, MCN CC-2308, Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA
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45
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Orellana ER, Jamis C, Horvath N, Hajnal A. Effect of vertical sleeve gastrectomy on alcohol consumption and preferences in dietary obese rats and mice: A plausible role for altered ghrelin signaling. Brain Res Bull 2018; 138:26-36. [PMID: 28802901 PMCID: PMC6537102 DOI: 10.1016/j.brainresbull.2017.08.004] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Revised: 08/05/2017] [Accepted: 08/07/2017] [Indexed: 12/13/2022]
Abstract
Vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) are the most common surgical options for the treatment of obesity and metabolic disorder. Whereas RYGB may result in greater and more durable weight loss, recent clinical and pre-clinical studies in rats have raised concerns that RYGB surgery may increase risk for alcohol use disorder (AUD). In contrast, recent clinical reports suggest a lesser risk for AUD following VSG, although no preclinical studies have been done to confirm that. Therefore, the present study sought to determine the effects of VSG on ethanol intake and preferences in rodent models using protocols similar to those previously used in animal studies for RYGB. Male Sprague Dawley rats and male C57B6 mice were made obese on a high fat diet (60%kcal from fat) and received VSG or no surgery (controls). All animals then were given access to increasing concentrations of ethanol (2%, 4%, 6%, and 8%), presented for few days each. Compared to controls, VSG rats consumed significantly less of 2, 6 and 8% ethanol and showed significantly reduced preferences to 6 and 8% ethanol over water. VSG mice also displayed reduced intake and preference for 6 and 8% ethanol solutions. After a two-week period of forced abstinence, 8% ethanol was reintroduced and the VSG rats and mice continued to exhibit reduced consumption and less preference for ethanol. Regarding the underlying mechanism, we hypothesized that the removal of the ghrelin producing part of the stomach in the VSG surgery is a possible contributor to the observed reduced ethanol preference. To test for functional changes at the ghrelin receptors, the VSG and control rats were given IP injections of acyl-ghrelin (2.5nmol and 5nmol) prior to ethanol access. Neither concentration of ghrelin resulted in a significant increase in 8% ethanol consumption of VSG or control subjects. Next, the rats were given IP injections of the ghrelin receptor antagonist, JMV (2.5mg/kg body weight). This dose induced a significant reduction in 8% ethanol consumption in the VSG group, but no effect on ethanol intake in the controls. While ghrelin injection was uninformative, increased sensitivity to subthreshold doses of the ghrelin receptor antagonist may indicate reduced ghrelin signaling following VSG. Overall, these findings suggest that bariatric patients with increased susceptibility to AUD may benefit from receiving VSG instead of RYGB surgery, and that changes in ghrelin signaling, at least in part, may play a role in the differential AUD risks between the two most commonly performed bariatric surgical procedures.
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Affiliation(s)
- Elise R Orellana
- Department of Neural and Behavioral Sciences, The Pennsylvania State University, College of Medicine, Hershey, PA, 17033, USA
| | - Catherine Jamis
- Department of Neural and Behavioral Sciences, The Pennsylvania State University, College of Medicine, Hershey, PA, 17033, USA
| | - Nelli Horvath
- Department of Neural and Behavioral Sciences, The Pennsylvania State University, College of Medicine, Hershey, PA, 17033, USA
| | - Andras Hajnal
- Department of Neural and Behavioral Sciences, The Pennsylvania State University, College of Medicine, Hershey, PA, 17033, USA.
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Jerlhag E. GLP-1 signaling and alcohol-mediated behaviors; preclinical and clinical evidence. Neuropharmacology 2018; 136:343-349. [PMID: 29337226 DOI: 10.1016/j.neuropharm.2018.01.013] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2017] [Revised: 12/18/2017] [Accepted: 01/09/2018] [Indexed: 12/20/2022]
Abstract
Alcohol addiction, affecting approximately four percent of the population, contributes significantly to the global burden of diseases and is a substantial cost to the society. The neurochemical mechanisms regulating alcohol mediated behaviors is complex and in more recent years a new physiological role of the gut-brain peptides, traditionally known to regulate appetite and food intake, have been suggested. Indeed, regulators of alcohol-mediated behaviors. One of these gut-brain peptides is the annorexigenic peptide glucagon-like peptide-1 (GLP-1), Preclinical studies show that GLP-1 receptor activation, either by GLP-1 or analogues, attenuate the ability of alcohol to activate the mesolimbic dopamine system as well as decrease alcohol consumption and operant self-administration. In further support for the endogenous GLP-1 system in addiction processes are the experimental data showing that a GLP-1 receptor antagonist increases alcohol intake. Moreover, GLP-1 receptor agonists prevent the ability of other addictive drugs to activate the mesolimbic dopamine system. The number of clinical studies is limited, but show i) that genetic variation in the GLP-1 receptor gene is associated with alcohol addiction as well as increased alcohol infusion in humans, ii) that plasma levels of GLP-1 are associated with the subjective experience of cocaine and iii) that a GLP-1 receptor agonist reduces alcohol intake in patients with type-2 diabetes mellitus. These experimental and clinical studies raises the concern that clinically available GLP-1 receptor agonists deserves to be tested as potential treatments of patients with addictive disorders including alcohol addiction. This article is part of the Special Issue entitled 'Metabolic Impairment as Risk Factors for Neurodegenerative Disorders.'
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Affiliation(s)
- Elisabet Jerlhag
- Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Medicinaregatan 13A, SE-405 30 Gothenburg, Sweden.
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Blackburn AN, Hajnal A, Leggio L. The gut in the brain: the effects of bariatric surgery on alcohol consumption. Addict Biol 2017; 22:1540-1553. [PMID: 27578259 DOI: 10.1111/adb.12436] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2016] [Revised: 06/15/2016] [Accepted: 07/14/2016] [Indexed: 12/19/2022]
Abstract
Obesity represents a major medical and public health problem worldwide. Efforts have been made to develop novel treatments, and among them bariatric surgery is used as an effective treatment to achieve significant, long-term weight loss and alleviate medical problems related to obesity. Alcohol use disorder (AUD) is also a leading cause of morbidity and mortality worldwide. Recent clinical studies have revealed a concern for bariatric surgery patients developing an increased risk for alcohol consumption, and for AUD. A better understanding of the relationship between bariatric surgery and potential later development of AUD is important, given the critical need of identifying patients at high risk for AUD. This paper reviews current clinical and basic science research and discusses potential underlying mechanisms. Special emphasis in this review is given to recent work suggesting that, alterations in alcohol metabolism/pharmacokinetics resulting from bariatric surgery are unlikely to be the primary or at least the only explanation for increased alcohol use and development of AUD, as changes in brain reward processing are also likely to play an important role. Additional studies are needed to clarify the potential role and mechanisms of how bariatric surgery may increase alcohol use and lead to AUD development.
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Affiliation(s)
- Ashley N. Blackburn
- Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology; National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health; Bethesda MD USA
| | - Andras Hajnal
- Department of Neural and Behavioral Sciences; Pennsylvania State University College of Medicine; PA USA
| | - Lorenzo Leggio
- Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology; National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health; Bethesda MD USA
- Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences; Brown University; Providence RI USA
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48
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Zallar LJ, Farokhnia M, Tunstall BJ, Vendruscolo LF, Leggio L. The Role of the Ghrelin System in Drug Addiction. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2017; 136:89-119. [PMID: 29056157 DOI: 10.1016/bs.irn.2017.08.002] [Citation(s) in RCA: 68] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
In the past years, a significant volume of research has implicated the appetitive hormone ghrelin in the mechanisms underlying drug use and addiction. From a neuroscientific standpoint, ghrelin modulates both reward and stress pathways, two key drivers of substance use behaviors. Previous investigations support a connection between the ghrelin system and alcohol, stimulants, and tobacco use in both animals and humans, while the research on opioids and cannabis is scarce. In general, upregulation of the ghrelin system seems to enhance craving for drugs as well as substances use. On the other hand, acute and chronic exposure to drugs of abuse influences the ghrelin system at different levels. This chapter summarizes the literature on the relationship between the ghrelin system and substance-related behaviors. We also review recent work investigating the ghrelin system as a potential pharmacological target for treating substance use disorders and discuss the need for additional research.
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Affiliation(s)
- Lia J Zallar
- Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, United States; Neurobiology of Addiction Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, United States
| | - Mehdi Farokhnia
- Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, United States
| | - Brendan J Tunstall
- Neurobiology of Addiction Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, United States
| | - Leandro F Vendruscolo
- Neurobiology of Addiction Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, United States
| | - Lorenzo Leggio
- Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, United States; Center for Alcohol and Addiction Studies, Brown University, Providence, RI, United States.
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49
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Sirohi S, Richardson BD, Lugo JM, Rossi DJ, Davis JF. Impact of Roux-en-Y gastric bypass surgery on appetite, alcohol intake behaviors, and midbrain ghrelin signaling in the rat. Obesity (Silver Spring) 2017; 25:1228-1236. [PMID: 28500684 PMCID: PMC6029700 DOI: 10.1002/oby.21839] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2017] [Accepted: 02/28/2017] [Indexed: 12/30/2022]
Abstract
OBJECTIVE Roux-en-Y gastric bypass (RYGB) surgery reduces appetite and stimulates new onset alcohol misuse; however, the genesis of these behavioral changes is unclear. This study is hypothesized that new onset alcohol intake is a behavioral adaptation that occurs secondary to reduced appetite and correlates with altered central ghrelin signaling. METHODS Hedonic high-fat diet (HFD) intake was evaluated prior to the assessment of alcohol intake behaviors in RYGB and control rats. Measurements were also taken of circulating ghrelin and ghrelin receptor (GHSR) regulation of neuronal firing in ventral tegmental area (VTA) dopamine (DA) neurons. RESULTS RYGB rats displayed reduced HFD intake relative to controls. Sham and RYGB rats consumed more alcohol and preferred lower concentrations of alcohol, whereas only RYGB rats escalated alcohol intake during acute withdrawal. Remarkably, GHSR activity, independent of peripheral ghrelin release, set the tonic firing of VTA DA neurons, a response selectively diminished in RYGB rats. CONCLUSIONS This study indicates that gut manipulations lead to increased alcohol intake, whereas RYGB promotes behaviors that may maintain alcohol misuse. Reductions in hedonic feeding and diminished GHSR control of VTA firing further distinguish gut manipulation from complete bypass and present a potential mechanism linking reduced appetite with alcohol misuse after RYGB surgery.
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Affiliation(s)
- Sunil Sirohi
- Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, Washington, USA
| | - Ben D Richardson
- Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, Washington, USA
| | - Janelle M Lugo
- Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, Washington, USA
| | - David J Rossi
- Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, Washington, USA
| | - Jon F Davis
- Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, Washington, USA
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50
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Spadola CE, Wagner EF, Accornero VH, Vidot DC, de la Cruz-Munoz N, Messiah SE. Alcohol use patterns and alcohol use disorders among young adult, ethnically diverse bariatric surgery patients. Subst Abus 2016; 38:82-87. [DOI: 10.1080/08897077.2016.1262305] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- Christine E. Spadola
- Robert Stempel College of Public Health and Social Work, Florida International University, Miami, Florida, USA
| | - Eric F. Wagner
- Robert Stempel College of Public Health and Social Work, Florida International University, Miami, Florida, USA
| | - Veronica H. Accornero
- Department of Pediatrics, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Denise C. Vidot
- Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, Florida, USA
| | | | - Sarah E. Messiah
- Department of Pediatrics, University of Miami Miller School of Medicine, Miami, Florida, USA
- Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, Florida, USA
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