Natural Bitter Compounds, Intestinal TAS2Rs, and GLP-1 Secretion: Mechanistic Evidence and Translational Challenges
- 1College of Food Science and Technology, Hebei Normal University of Science and Technology, Qinhuangdao 066000, China
- 2Department of Nutrition and Health, China Agricultural University, Beijing 100091, China
- 3College of Animal Science and Technology, Hebei Normal University of Science and Technology, Qinhuangdao 066000, China
Abstract
Bitter taste receptors (TAS2Rs) are expressed beyond the oral cavity, and those in the intestine have been implicated in metabolic regulation. Selected natural bitter compounds (NBCs) increase glucagon-like peptide-1 (GLP-1) release in experimental enteroendocrine models, but predicted ligand binding, functional receptor activation, and receptor-dependent hormone secretion do not provide equivalent evidence. Intestinal TAS2Rs may thus provide a route to endogenous GLP-1 modulation distinct from receptor agonist therapy. Unlike broader reviews of extraoral chemosensing, this review maps these distinct endpoints for individual NBC-TAS2R pairs and separates measured GLP-1 release from changes in proglucagon expression. We define a receptor-supported enteroendocrine core and distinguish it from indirect evidence and testable hypotheses concerning microbiota-associated, immune–endocrine, and gut–brain interfaces. Receptor-directed perturbation supports selected compound-specific secretory responses, whereas the three proposed interfaces lack complete NBC-TAS2R-GLP-1 causal chains. We critically compare human-derived cell lines, animal models, primary tissues, and organoids, and summarize the experimental concentrations and GLP-1 assay endpoints where reported. Finally, we identify priorities for receptor-selective validation, measurement of intestinal target-site exposure, and prospective human studies. This evidence map clarifies what is experimentally supported and what must be demonstrated before intestinal TAS2Rs can be considered reliable targets for endogenous GLP-1 modulation.
Related
- Dynamic three-dimensional chromatin remodeling in lung disease: mechanistic principles, pathogenic regulatory networks, and translational challenges
- Natural Bioactive Compounds Targeting Gut Barrier Integrity and Metabolic Endotoxemia in Cardiometabolic Disease: Mechanistic Insights and Translational Perspectives
- Panax ginseng Across the Cardiovascular Continuum: Molecular Targets, Mechanistic Convergence, and Translational Challenges
- Single-cell Transcriptomics in Autoimmune Diseases: Mechanistic Insights, Cross-disease Convergence, and Translational Challenges in Rheumatoid Arthritis, Systemic Lupus Erythematosus, Type 1 Diabetes, and Multiple Sclerosis.
- New Advances in Bioactive Compounds in Health and Disease: From Molecular Mechanisms to Translational Perspectives
BibTeX
@article{lao2026natural,
title = {{Natural Bitter Compounds, Intestinal TAS2Rs, and GLP-1 Secretion: Mechanistic Evidence and Translational Challenges}},
author = {Wenmin Lao and Xiaojing Liu and Jiefang Zhou and Fengmei Zhu and Jun Li and Wentao Xu and Yongsheng Liu},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms27219816},
url = {https://www.mdpi.com/1422-0067/27/21/9816},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Natural Bitter Compounds, Intestinal TAS2Rs, and GLP-1 Secretion: Mechanistic Evidence and Translational Challenges
AU - Wenmin Lao
AU - Xiaojing Liu
AU - Jiefang Zhou
AU - Fengmei Zhu
AU - Jun Li
AU - Wentao Xu
AU - Yongsheng Liu
PY - 2026
DA - 2026/11/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219816
UR - https://www.mdpi.com/1422-0067/27/21/9816
AB - Bitter taste receptors (TAS2Rs) are expressed beyond the oral cavity, and those in the intestine have been implicated in metabolic regulation. Selected natural bitter compounds (NBCs) increase glucagon-like peptide-1 (GLP-1) release in experimental enteroendocrine models, but predicted ligand binding, functional receptor activation, and receptor-dependent hormone secretion do not provide equivalent evidence. Intestinal TAS2Rs may thus provide a route to endogenous GLP-1 modulation distinct from receptor agonist therapy. Unlike broader reviews of extraoral chemosensing, this review maps these distinct endpoints for individual NBC-TAS2R pairs and separates measured GLP-1 release from changes in proglucagon expression. We define a receptor-supported enteroendocrine core and distinguish it from indirect evidence and testable hypotheses concerning microbiota-associated, immune–endocrine, and gut–brain interfaces. Receptor-directed perturbation supports selected compound-specific secretory responses, whereas the three proposed interfaces lack complete NBC-TAS2R-GLP-1 causal chains. We critically compare human-derived cell lines, animal models, primary tissues, and organoids, and summarize the experimental concentrations and GLP-1 assay endpoints where reported. Finally, we identify priorities for receptor-selective validation, measurement of intestinal target-site exposure, and prospective human studies. This evidence map clarifies what is experimentally supported and what must be demonstrated before intestinal TAS2Rs can be considered reliable targets for endogenous GLP-1 modulation.
SN - 1422-0067
ER -