Journal
NATURE MICROBIOLOGY
Volume 6, Issue 5, Pages 563-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41564-021-00880-5
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Funding
- National Research Foundation of Korea (NRF) [NRF-2018R1A2A1A05078258]
- Global Ph.D. Fellowship program
- NRF grant - Korean government [NRF-2018H1A2A1061914]
- National Research Foundation of Korea [2018H1A2A1061914] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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The study demonstrates that Akkermansia muciniphila increases thermogenesis and GLP-1 secretion in mice by inducing uncoupling protein 1. A protein secreted by A. muciniphila, P9, interacts with ICAM-2 and can target metabolic diseases. This interaction could be a potential therapeutic target for such diseases.
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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