The Intricate Relationship between Circadian Rhythms and Gastrointestinal Peptides in Obesity
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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2 of the 169 references couldn’t be matched to a known paper.
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Reytor-González, C., Simancas-Racines, D., Román-Galeano, N. M., Annunziata, G., Galasso, M., Zambrano-Villacres, R., Verde, L., Muscogiuri, G., Frias-Toral, E., & Barrea, L. (2025) · Nutrients · doi:10.3390/nu17132135 · Cited by 88 · see citing works
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“In parallel, leptin regulates glucose homeostasis by inhibiting hepatic gluconeogenesis, an effect dependent on IL-6 and hepatic STAT3 [84].”
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Thermal challenge and food intake: Mutual regulatory mechanisms
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Unraveling the Tapestry of Health: The Intricate Dance of Circadian Rhythms and Human Diseases
Parvez, S., Džupina, A., Fatima, G., Hadi, N. R., Fedačko, J., Magomedova, A. G., Raza, A. M., Yousif, N. G., & Al-Hmadi, H. B. (2026) · Bratislavské lekárske listy/Bratislava medical journal · doi:10.1007/s44411-025-00480-3
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Investigating Overweight and Obesity Risk in Shift Workers Using Omics Technologies
Scionti, K., Vaclavkova, I., Schoissengeier, V., & Wagner, K. (2026) · Obesity Reviews · doi:10.1111/obr.70233
- 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
- Licence
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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