Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice
Abstract
The gut microbiota, which includes Akkermansia muciniphila, is known to modulate energy metabolism, glucose tolerance, immune system maturation and function in humans 1-4. Although A. muciniphila is correlated with metabolic diseases and its beneficial causal effects were reported on host metabolism 5-8, the molecular mechanisms involved have not been identified. Here, we report that A. muciniphila increases thermogenesis and glucagon-like peptide-1 (GLP-1) secretion in high-fat-diet (HFD)-induced C57BL/6J mice by induction of uncoupling protein 1 in brown adipose tissue and systemic GLP-1 secretion. We apply fast protein liquid chromatography and liquid chromatography coupled to mass spectrophotometry analysis to identify an 84 kDa protein, named P9, that is secreted by A. muciniphila. Using L cells and mice fed on an HFD, we show that purified P9 alone is sufficient to induce GLP-1 secretion and brown adipose tissue thermogenesis. Using ligand-receptor capture analysis, we find that P9 interacts with intercellular adhesion molecule 2 (ICAM-2). Interleukin-6 deficiency abrogates the effects of P9 in glucose homeostasis and downregulates ICAM-2 expression. Our results show that the interactions between P9 and ICAM-2 could be targeted by therapeutics for metabolic diseases.
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GLP-1 secretion is modulated by the gut microbiota and multiple gut microbiota-derived metabolites, including SCFAs, secondary BAs, indoles, and PUFAs.
“The secretion of GLP-1 is modulated by the gut microbiota”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [599]
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- Authors
- Yoon, H. S., Cho, C. H., Yun, M. S., Jang, S. J., You, H. J., Kim, J.-H., Han, D., Cha, K. H., Moon, S. H., Lee, K., Kim, Y.-J., Lee, S.-J., Nam, T.-W., & Ko, G.
- Affiliations
- Seoul National University (KR)
- Korea University (KR)
- Corresponding author
- Ko, GwangPyo
- ORCID
- Venue
- Nature Microbiology
- Published
- 2021-04-05
- Volume
- 6
- Issue
- 5
- Pages
- 563-573
- ISSN
- 2058-5276 (ISSN-L)
- OpenAlex
- W3149804258
- Cited by
- 602
- References
- 72
- Citations by year
- 2026: 108 · 2025: 148 · 2024: 119 · 2023: 106 · 2022: 94 · 2021: 27
- FWCI
- 27.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Research Foundation of Korea (NRF-2018R1A2A1A05078258, NRF-2018H1A2A1061914)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- Akkermansia muciniphila, glucagon-like peptide-1 secretion, brown adipose tissue thermogenesis, UCP1, ICAM-2, interleukin-6, high-fat diet, glucose homeostasis, gut microbiota, metabolic disorders, host-microbe interactions
- MeSH terms
- Gastrointestinal Microbiome, Uncoupling Protein 1, Akkermansia, Animals, Bacterial Proteins, Adipose Tissue, Brown, Glucose, Homeostasis, Humans, Male, Metabolic Diseases, Mice, Inbred C57BL, Antigens, CD, Cell Adhesion Molecules, Mice, Glucagon-Like Peptide 1, Diet, High-Fat
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