The Connection Between the Appetite-Regulatory Peptides Ghrelin and GLP-1 and Alcohol Use Disorder

May 29, 2025Advances in experimental medicine and biology

Links Between Appetite Hormones Ghrelin and GLP-1 and Alcohol Use Disorder

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Abstract

Preclinical studies indicate that central ghrelin infusions elevate alcohol intake, while ghrelin receptor suppression reduces alcohol-related responses.

The ghrelin pathway includes several substrates that may influence alcohol consumption.
Endogenous GHSR inverse agonist LEAP2 and ghrelin precursor DAG block the stimulatory effects of alcohol and reduce intake.
GLP-1 receptor agonists, approved for type 2 diabetes and obesity, have shown potential in reducing alcohol-related responses in rodents.
In animal models of alcohol use disorder, GLP-1 receptor agonists decrease alcohol intake and motivation, and prevent relapse drinking.
Certain brain areas associated with reward are implicated in the modulation of alcohol-related responses by ghrelin and GLP-1.

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The body-brain connection is well-established, further evidenced by studies on the orexigenic peptide ghrelin and the anorexigenic peptide glucagon-like peptide-1 (GLP-1). The ghrelin pathway consists of several substrates, which has been studied in relation to alcohol-related responses. Preclinical studies have found that central ghrelin infusions elevate alcohol intake, whereas suppression of the ghrelin receptors (GHSR) attenuates alcohol-related responses. On a similar note, the endogenous GHSR inverse agonist, LEAP2, and the precursor of ghrelin, DAG, block the stimulatory properties of alcohol and reduce alcohol intake. GLP-1 receptor agonists are currently approved for the treatment of type 2 diabetes and obesity. Recent advances in rodents have extended the pharmacological relevance of these GLP-1 receptor agonists as they mitigate alcohol-related responses. Specifically, in animal models reflecting alcohol use disorder (AUD) all tested GLP-1 receptor agonists reduce alcohol intake, suppress the motivation to consume alcohol, and prevent relapse drinking, effects most likely driven by an attenuation of alcohol-induced reward. Additional experiments were conducted in attempts to define areas and circuits responsible for ghrelin and GLP-1 to control alcohol-related responses. Specifically, areas associated with reward were defined as important modulatory areas. In summary, the ghrelin pathway and GLP-1 participate in the pathophysiology of AUD, thereby providing tentative treatment targets.

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The Connection Between the Appetite-Regulatory Peptides Ghrelin and GLP-1 and Alcohol Use Disorder

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