Cited by 9Regulation of Appetite and ObesityCircadian rhythm and melatoninHypothalamic control of reproductive hormones

The Intricate Relationship between Circadian Rhythms and Gastrointestinal Peptides in Obesity

Ribeiro, Filipe M., Arnaldo, Luiz, P. Milhomem, Lana, S. Aguiar, Samuel, Franco, Octavio L.·2025·Peptides

Abstract

There are different molecular pathways that regulate appetite, particularly the role of the hypothalamus, circadian rhythms, and gastrointestinal peptides. The hypothalamus integrates signals from orexigenic peptides like neuropeptide Y (NPY) and agouti-related protein (AgRP), which stimulate appetite, and anorexigenic peptides such as pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART), which promote satiety. These signals are influenced by peripheral hormones like leptin, ghrelin, insulin, and cortisol, as well as gut peptides including glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and cholecystokinin (CCK). The circadian rhythm, regulated by proteins like circadian locomotor output cycles kaput (CLOCK) and brain and muscle ARNT-like 1 (BMAL1), modulates the secretion of these peptides, aligning feeding behaviors with the sleep-wake cycle. In obesity, these regulatory systems are disrupted, leading to leptin resistance, increased ghrelin sensitivity, and altered gut peptide secretion. This results in heightened appetite and impaired satiety, contributing to overeating and metabolic dysfunction. Additionally, circadian disruptions further impair metabolic processes, exacerbating obesity. The present article underscores the importance of understanding the molecular interplay between circadian rhythms and gastrointestinal peptides, particularly in the context of obesity. While some molecular interactions, such as the regulation of GLP-1 and PYY by reverberation of circadian rhythm α (REV-ERBα) and retinoic acid-related orphan receptor α (RORα), are well-established, clinical studies are scarce. Future research is expected to explore these pathways in obesity management, especially with the rise of incretin-based treatments like semaglutide. A deeper understanding of hypothalamic molecular mechanisms could lead to novel pharmacological and non-pharmacological therapies for obesity.

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Crossref · 10.1016/j.peptides.2025.171356

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Authors
Ribeiro, F. M., Arnaldo, L., P. Milhomem, L., S. Aguiar, S., & Franco, O. L.
Affiliations
Universidade Católica de Brasília (BR)
Venue
Peptides
Publisher
Elsevier BV
Published
2025-03
Volume
185
Pages
171356
ISSN
0196-9781 (ISSN-L)
OpenAlex
W4407269607
Cited by
9
References
169
Citations by year
2026: 6 · 2025: 3
FWCI
1.01
Type
journal article
Language
en
Open access
closed
Locations
  • Peptides (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Fundação de Apoio à Pesquisa do Distrito Federal (00193-00000769/2021-12)
  • Fundação de Apoio ao Desenvolvimento do Ensino, Ciência e Tecnologia do Estado de Mato Grosso do Sul (71/700.102/2018)
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (2481/2022 / 88881.710548/2022-01)
  • Financiadora de Estudos e Projetos (2673.22)
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (465507/2014-0)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords
circadian rhythm, gastrointestinal peptides, obesity, appetite regulation, hypothalamus, neuropeptide Y, agouti-related protein, proopiomelanocortin, cocaine- and amphetamine-regulated transcript, leptin resistance, ghrelin, glucagon-like peptide-1, peptide YY, cholecystokinin, clocks, Bmal1, NR1D1, RORα, semaglutide, incretin-based therapy, satiety
MeSH terms
Animals, Circadian Rhythm, Gastrointestinal Hormones, Humans, Hypothalamus, Obesity, Peptide YY, Glucagon-Like Peptide 1

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