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Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice
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Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice
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Journal Article
Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice
2021
Overview
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.
Akkermansia muciniphila
produces P9, a small protein that interacts with intercellular adhesion molecule 2 to increase thermogenesis and glucagon-like peptide-1 secretion in mice.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
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/ Adipose Tissue, Brown - metabolism
/ Animals
/ Bacterial Proteins - genetics
/ Bacterial Proteins - metabolism
/ Biomedical and Life Sciences
/ Cell Adhesion Molecules - genetics
/ Cell Adhesion Molecules - metabolism
/ Diet, High-Fat - adverse effects
/ Glucagon
/ Glucagon-Like Peptide 1 - genetics
/ Glucagon-Like Peptide 1 - metabolism
/ Glucose
/ Humans
/ L cells
/ Letter
/ Male
/ Metabolic Diseases - genetics
/ Metabolic Diseases - metabolism
/ Metabolic Diseases - microbiology
/ Mice
/ Peptides
/ Proteins
/ Uncoupling Protein 1 - genetics
/ Uncoupling Protein 1 - metabolism
/ Virology
