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

April 05, 2021


Nature Microbiol (2021) https://doi.org/10.1038/s41564-021-00880-5


Here, we report that A. muciniphila increases thermogenesis and gluc.-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.


Hyo Shin Yoon, Chung Hwan Cho, Myeong Sik Yun, Sung Jae Jang, Hyun Ju You, Jun-hyeong Kim, Dohyun Han, Kwang Hyun Cha, Sung Hyun Moon, Kiuk Lee, Yeon-Ji Kim, Sung-Joon Lee, Tae-Wook Nam & GwangPyo Ko