Yoon, Hyo Shin Cho, Chung Hwan Yun, Myeong Sik Jang, Sung Jae You, Hyun Ju Kim, Jun-hyeong Han, Dohyun Cha, Kwang Hyun Moon, Sung Hyun Lee, Kiuk Kim, Yeon-Ji Lee, Sung-Joon Nam, Tae-Wook Ko, GwangPyo 2024-01-19T15:00:32Z 2024-01-19T15:00:32Z 2021-09-05 2021-05 2058-5276 https://pubs.kist.re.kr/handle/201004/117082 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. English NATURE RESEARCH Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice Article 10.1038/s41564-021-00880-5 1 NATURE MICROBIOLOGY, v.6, no.5, pp.563 - + NATURE MICROBIOLOGY 6 5 563 + scie scopus 000636919500001 2-s2.0-85103672935 Microbiology Microbiology Article Akkermansia muciniphila glucose homeostasis metabolic disease gut microbiota