Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice

Authors
Yoon, Hyo ShinCho, Chung HwanYun, Myeong SikJang, Sung JaeYou, Hyun JuKim, Jun-hyeongHan, DohyunCha, Kwang HyunMoon, Sung HyunLee, KiukKim, Yeon-JiLee, Sung-JoonNam, Tae-WookKo, GwangPyo
Issue Date
2021-05
Publisher
NATURE RESEARCH
Citation
NATURE MICROBIOLOGY, v.6, no.5, pp.563 - +
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.
Keywords
Akkermansia muciniphila; glucose homeostasis; metabolic disease; gut microbiota
ISSN
2058-5276
URI
https://pubs.kist.re.kr/handle/201004/117082
DOI
10.1038/s41564-021-00880-5
Appears in Collections:
KIST Article > 2021
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