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

Featured Paper of the Month – September 2021

Study authors Sara Deschaine and Mehdi Farokhnia

Published in Addiction Biology by Sara Deschaine, Mehdi Farokhnia and Lorenzo Leggio et al. in the NIDA IRP Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section.

Summary

Growing evidence shows that ghrelin, a gastric-derived peptide hormone, is involved in regulation of alcohol seeking behavior. Accordingly, the ghrelin system is being studies as a potential pharmacotherapeutic target for alcohol use disorder (AUD). The reverse side of this bidirectional link, i.e., the effects that alcohol may have on the ghrelin system, is not well understood. In a series of preclinical and clinical experiments, the present study aimed to investigate the impact of alcohol on different elements of the ghrelin system. It was found that peripheral 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, and this effect was not dependent on the ghrelin receptor. No dose-dependent effects of alcohol were observed on acyl-ghrelin secretion from gastric mucosa cells or on ghrelin-O-acyltransferase (GOAT) acylation activity. Lastly, alcohol and sucrose produced distinct effects on ghrelin in rats despite equivalent caloric value. These 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 Information

Deschaine, Sara L; Farokhnia, Mehdi; Gregory-Flores, Adriana; Zallar, Lia J; You, Zhi-Bing; Sun, Hui; Harvey, Deon M; Marchette, Renata C N; Tunstall, Brendan J; Mani, Bharath K; Moose, Jacob E; Lee, Mary R; Gardner, Eliot; Akhlaghi, Fatemeh; Roberto, Marisa; Hougland, James L; Zigman, Jeffrey M; Koob, George F; Vendruscolo, Leandro F; Leggio, Lorenzo

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

In: Addict Biol, pp. e13033, 2021, ISSN: 1369-1600.

Abstract | Links

@article{pmid33908131,

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

author = {Sara L Deschaine and Mehdi Farokhnia and Adriana Gregory-Flores and Lia J Zallar and Zhi-Bing You and Hui Sun and Deon M Harvey and Renata C N Marchette and Brendan J Tunstall and Bharath K Mani and Jacob E Moose and Mary R Lee and Eliot Gardner and Fatemeh Akhlaghi and Marisa Roberto and James L Hougland and Jeffrey M Zigman and George F Koob and Leandro F Vendruscolo and Lorenzo Leggio},

url = {https://pubmed.ncbi.nlm.nih.gov/33908131/},

doi = {10.1111/adb.13033},

issn = {1369-1600},

year  = {2021},

date = {2021-04-01},

urldate = {2021-04-01},

journal = {Addict Biol},

pages = {e13033},

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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}