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

Cited 226 time in Web of Science Cited 247 time in Scopus

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

Issue Date
Nature Microbiology, Vol.6 No.5, pp.563-573
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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  • College of Human Ecology
  • Department of Food and Nutrition
Research Area Biochemistry & Molecular Biology, Food Science & Technology, Microbiology, 미생물학, 분자생물학, 식품공학


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