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Cited by 33Regulation of Appetite and ObesityNeurotransmitter Receptor Influence on BehaviorNeural and Behavioral Psychology Studies

How gut hormones shape reward: A systematic review of the role of ghrelin and GLP-1 in human fMRI

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Schulz, Corinna, Vezzani, Cecilia, Kroemer, Nils B.·2023·Physiology & Behavior
DOI 10.1016/j.physbeh.2023.114111

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Abstract

The gastrointestinal hormones ghrelin and glucagon-like peptide-1 (GLP-1) have opposite secretion patterns, as well as opposite effects on metabolism and food intake. Beyond their role in energy homeostasis, gastrointestinal hormones have also been suggested to modulate the reward system. However, the potential of ghrelin and GLP-1 to modulate reward responses in humans has not been systematically reviewed before. To evaluate the convergence of published results, we first conduct a multi-level kernel density meta-analysis of studies reporting a positive association of ghrelin (N comb = 353, 18 contrasts) and a negative association of GLP-1 (N comb = 258, 12 contrasts) and reward responses measured using task functional magnetic resonance imaging (fMRI). Second, we complement the meta-analysis using a systematic literature review, focusing on distinct reward phases and applications in clinical populations that may account for variability across studies. In line with preclinical research, we find that ghrelin increases reward responses across studies in key nodes of the motivational circuit, such as the nucleus accumbens, pallidum, putamen, substantia nigra, ventral tegmental area, and the dorsal mid insula. In contrast, for GLP-1, we did not find sufficient convergence in support of reduced reward responses. Instead, our systematic review identifies potential differences of GLP-1 on anticipatory versus consummatory reward responses. Based on a systematic synthesis of available findings, we conclude that there is considerable support for the neuromodulatory potential of gut-based circulating peptides on reward responses. To unlock their potential for clinical applications, it may be useful for future studies to move beyond anticipated rewards to cover other reward facets.

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  • Data continue to grow on possible use for GLP-1 receptor agonists for addiction disorders, including clinical trial findings for alcohol use disorder.

    “data continue to grow on a possible use for GLP-1 receptor agonists for addiction disorders, which include clinical trial findings for alcohol use disorder.[24][25][26][27]”

    From Trends in glucagon-like peptide 1 receptor agonist use, 2014 to 2022. (2024) · cites this paper as [26]

    The ‘Diversity of clinical population’ section identifies substance use disorders as a potential treatment area for metabolic hormones, including GLP-1, but says research is needed to evaluate that possibility. The ‘Drug addiction’ section discusses alcohol-dependence findings involving ghrelin, not GLP-1 receptor agonists. Our copy does not report GLP-1 agonist clinical trial findings for alcohol use disorder or establish that evidence for their use in addiction is growing. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Improvement in diabetes management attributable to GLP-1 receptor agonists may reduce utilization of other diabetes treatment medications, including insulins.

    “Improvement in diabetes management attributable to GLP-1 receptor agonists may reduce utilization of other diabetes treatment medications, including insulins”

    From Trends in glucagon-like peptide 1 receptor agonist use, 2014 to 2022. (2024) · cites this paper as [20]

    The section “GLP-1 and its central effects” says GLP-1 analogs are used to treat type 2 diabetes, and section 2.2.1 discusses insulin secretion and food-reward responses. Neither section addresses whether GLP-1 receptor agonists reduce use of other diabetes medications, including insulin; searches for medication use and insulin requirements found no such passage in our copy. Page numbers were not available. (LLM, conf=0.72)

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Cited by

Sorted by citations

Authors
Schulz, C., Vezzani, C., & Kroemer, N. B.
Affiliations
  • University of Tübingen (DE)
  • University of Bonn (DE)
Corresponding author
Kroemer, Nils B.
ORCID
Venue
Physiology & Behavior
Publisher
Elsevier BV
Published
2023-05
Volume
263
Pages
114111
ISSN
0031-9384 (ISSN-L)
DOI
10.1016/j.physbeh.2023.114111
OpenAlex
W4319073696
Cited by
33
References
22
Citations by year
2026: 8 · 2025: 13 · 2024: 8 · 2023: 4
FWCI
1.25
Type
journal article
Language
en
Open access
Licence
Locations
  • Physiology & Behavior (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
Deutsche Forschungsgemeinschaft (KR 4555/7–1, KR 4555/9–1)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords
ghrelin, glucagon-like peptide-1, gastrointestinal hormones, reward processing, nucleus accumbens, food intake regulation, energy homeostasis, gut-brain axis, neuromodulation
MeSH terms
Gastrointestinal Hormones, Humans, Magnetic Resonance Imaging, Reward, Glucagon-Like Peptide 1, Ghrelin

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