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To further characterize this relationship, we examined (1) ghrelin levels via secondary analysis of human laboratory alcohol administration experiments with heavy\u2010drinking participants; (2) expression of ghrelin, ghrelin receptor, and ghrelin\u2010O\u2010acyltransferase (GOAT) genes (\n                    <jats:italic>GHRL<\/jats:italic>\n                    ,\n                    <jats:italic>GHSR<\/jats:italic>\n                    , and\n                    <jats:italic>MBOAT4<\/jats:italic>\n                    , respectively) in post\u2010mortem brain tissue from individuals with alcohol use disorder (AUD) versus controls; (3) ghrelin levels in\n                    <jats:italic>Ghsr<\/jats:italic>\n                    knockout and wild\u2010type rats following intraperitoneal (i.p.) alcohol administration; (4) effect of alcohol on ghrelin secretion from gastric mucosa cells\n                    <jats:italic>ex vivo<\/jats:italic>\n                    and GOAT enzymatic activity\n                    <jats:italic>in vitro<\/jats:italic>\n                    ; and (5) ghrelin levels in rats following i.p. alcohol administration versus a calorically equivalent non\u2010alcoholic sucrose solution. Acyl\u2010 and total\u2010ghrelin levels decreased following acute alcohol administration in humans, but AUD was not associated with changes in central expression of ghrelin system genes in post\u2010mortem tissue. In rats, alcohol decreased acyl\u2010ghrelin, but not des\u2010acyl\u2010ghrelin, in both\n                    <jats:italic>Ghsr<\/jats:italic>\n                    knockout and wild\u2010type rats. No dose\u2010dependent effects of alcohol were observed on acyl\u2010ghrelin secretion from gastric mucosa cells or on GOAT acylation activity. Lastly, alcohol and sucrose produced distinct effects on ghrelin in rats despite equivalent caloric value. Our findings suggest that alcohol acutely decreases peripheral ghrelin concentrations\n                    <jats:italic>in vivo<\/jats:italic>\n                    , but not in proportion to alcohol's caloric value or through direct interaction with ghrelin\u2010secreting gastric mucosal cells, the ghrelin receptor, or the GOAT enzyme.\n                  <\/jats:p>","DOI":"10.1111\/adb.13033","type":"journal-article","created":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T00:45:57Z","timestamp":1619570757000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["A closer look at alcohol\u2010induced changes in the ghrelin system: novel insights from preclinical and clinical data"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3042-108X","authenticated-orcid":false,"given":"Sara L.","family":"Deschaine","sequence":"first","affiliation":[{"name":"Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Farokhnia","sequence":"additional","affiliation":[{"name":"Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Baltimore Maryland USA"},{"name":"Center on Compulsive Behaviors National Institutes of Health  Bethesda Maryland USA"},{"name":"Johns Hopkins Bloomberg School of Public Health Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Gregory\u2010Flores","sequence":"additional","affiliation":[{"name":"Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Baltimore Maryland USA"},{"name":"Neurobiology of Addiction Section, Intramural Research Program National Institute on Drug Abuse, National Institutes of Health  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lia J.","family":"Zallar","sequence":"additional","affiliation":[{"name":"Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Baltimore Maryland USA"},{"name":"Neurobiology of Addiction Section, Intramural Research Program National Institute on Drug Abuse, National Institutes of Health  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Bing","family":"You","sequence":"additional","affiliation":[{"name":"Neuropsychopharmacology Section, Molecular Targets and Medications Discovery Branch National Institute on Drug Abuse, National Institutes of Health  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Sun","sequence":"additional","affiliation":[{"name":"Clinical Core Laboratory, Office of the Clinical Director National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deon M.","family":"Harvey","sequence":"additional","affiliation":[{"name":"Office of the Scientific Director National Institute on Drug Abuse  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata C. 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