A closer look at alcohol-induced changes in the ghrelin system: novel insights from preclinical and clinical data

Authors

Sara L. Deschaine, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Mehdi Farokhnia, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Adriana Gregory-Flores, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Lia J. Zallar, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Zhi Bing You, National Institute on Drug Abuse (NIDA)
Hui Sun, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Deon M. Harvey, National Institute on Drug Abuse (NIDA)
Renata C.N. Marchette, National Institutes of Health (NIH)
Brendan J. Tunstall, National Institute on Drug Abuse (NIDA)
Bharath K. Mani, UT Southwestern Medical School
Jacob E. Moose, Syracuse University
Mary R. Lee, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Eliot Gardner, National Institute on Drug Abuse (NIDA)
Fatemeh Akhlaghi, University of Rhode Island
Marisa Roberto, Scripps Research Institute
James L. Hougland, Syracuse University
Jeffrey M. Zigman, UT Southwestern Medical School
George F. Koob, National Institute on Drug Abuse (NIDA)
Leandro F. Vendruscolo, National Institute on Drug Abuse (NIDA)
Lorenzo Leggio, National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Document Type

Article

Date of Original Version

1-1-2022

Abstract

Ghrelin is a gastric-derived peptide hormone with demonstrated impact on alcohol intake and craving, but the reverse side of this bidirectional link, that is, the effects of alcohol on the ghrelin system, remains to be fully established. To further characterize this relationship, we examined (1) ghrelin levels via secondary analysis of human laboratory alcohol administration experiments with heavy-drinking participants; (2) expression of ghrelin, ghrelin receptor, and ghrelin-O-acyltransferase (GOAT) genes (GHRL, GHSR, and MBOAT4, respectively) in post-mortem brain tissue from individuals with alcohol use disorder (AUD) versus controls; (3) ghrelin levels in Ghsr knockout and wild-type rats following intraperitoneal (i.p.) alcohol administration; (4) effect of alcohol on ghrelin secretion from gastric mucosa cells ex vivo and GOAT enzymatic activity in vitro; and (5) ghrelin levels in rats following i.p. alcohol administration versus a calorically equivalent non-alcoholic sucrose solution. Acyl- and total-ghrelin levels decreased following acute alcohol administration in humans, but AUD was not associated with changes in central expression of ghrelin system genes in post-mortem tissue. In rats, alcohol decreased acyl-ghrelin, but not des-acyl-ghrelin, in both Ghsr knockout and wild-type rats. No dose-dependent effects of alcohol were observed on acyl-ghrelin 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 in vivo, but not in proportion to alcohol's caloric value or through direct interaction with ghrelin-secreting gastric mucosal cells, the ghrelin receptor, or the GOAT enzyme.

Publication Title, e.g., Journal

Addiction Biology

Volume

27

Issue

1

Citation/Publisher Attribution

Deschaine, Sara L., Mehdi Farokhnia, Adriana Gregory-Flores, Lia J. Zallar, Zhi Bing You, Hui Sun, Deon M. Harvey, Renata C. Marchette, Brendan J. Tunstall, Bharath K. Mani, Jacob E. Moose, Mary R. Lee, Eliot Gardner, Fatemeh Akhlaghi, Marisa Roberto, James L. Hougland, Jeffrey M. Zigman, George F. Koob, Leandro F. Vendruscolo, and Lorenzo Leggio. "A closer look at alcohol-induced changes in the ghrelin system: novel insights from preclinical and clinical data." Addiction Biology 27, 1 (2022). doi: 10.1111/adb.13033.