| Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice | |
|---|---|
| 년도 | 2021 |
| 날짜 | 2021 May |
| 페이지 / 학회지명 |
6(5):563-573 / Nature Microbiology |
| 논문저자 | Hyo Shin Yoon # 1, Chung Hwan Cho # 1, Myeong Sik Yun 1, Sung Jae Jang 1, Hyun Ju You 1 2 3 4, Jun-Hyeong Kim 5, Dohyun Han 6, Kwang Hyun Cha 7, Sung Hyun Moon 1 5, Kiuk Lee 5, Yeon-Ji Kim 8, Sung-Joon Lee 8, Tae-Wook Nam 5, GwangPyo Ko 9 10 11 12 |
| Link |
https://www.nature.com/articles/s41564-021-00880-5
142회 연결
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1 Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Korea. 2 Institute of Health and Environment, Seoul National University, Seoul, Korea. 3 Bio-MAX/N-Bio, Seoul National University, Seoul, Korea. 4 Center for Human and Environmental Microbiome, Seoul National University, Seoul, Korea. 5 KoBioLabs Inc., Seoul, Korea. 6 Proteomics Core Facility, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea. 7 Natural Product Informatics Research Center, Korea Institute of Science and Technology, Gangneung, Korea. 8 Department of Biotechnology, College of Life Sciences and Biotechnology, School of Life Sciences and Biotechnology, Korea University, Seoul, Korea. 9 Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Korea. gko@snu.ac.kr. 10 Bio-MAX/N-Bio, Seoul National University, Seoul, Korea. gko@snu.ac.kr. 11 Center for Human and Environmental Microbiome, Seoul National University, Seoul, Korea. gko@snu.ac.kr. 12 KoBioLabs Inc., Seoul, Korea. gko@snu.ac.kr. #Contributed equally. Abstract The gut microbiota, which includes Akkermansia muciniphila, is known to modulate energy metabolism, glucose tolerance, immune system maturation and function in humans1-4. Although A. muciniphila is correlated with metabolic diseases and its beneficial causal effects were reported on host metabolism5-8, 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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