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Article

Vascular Adhesion Protein 1 Mediates Gut Microbial Flagellin-Induced Inflammation, Leukocyte Infiltration, and Hepatic Steatosis

1
Institute of Biomedicine, Faculty of Medicine, University of Turku, 20014 Turku, Finland
2
Medicity Research Laboratory, University of Turku, 20014 Turku, Finland
3
Department of Clinical Microbiology and Immunology, Turku University Hospital, 20521 Turku, Finland
4
Turku Centre for Biotechnology, 20014 Turku, Finland
5
Faculty of Sport and Health Sciences, University of Jyväskylä, 40014 Jyväskylä, Finland
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 7 November 2019 / Revised: 13 January 2021 / Accepted: 29 January 2021 / Published: 2 February 2021
Toll-like receptor 5 ligand, flagellin, and vascular adhesion protein 1 (VAP-1) are involved in non-alcoholic fatty liver disease. This study aimed to determine whether VAP-1 mediates flagellin-induced hepatic fat accumulation. The effects of flagellin on adipocyte VAP-1 expression were first studied in vitro. Then, flagellin (100 ng/mouse) or saline was intraperitoneally injected into C57BL/6J (WT) and C57BL/6-Aoc3-/- (VAP-1 KO) mice on a high-fat diet twice a week every 2 weeks for 10 weeks. After that, the effects on inflammation, insulin signaling, and metabolism were studied in liver and adipose tissues. Hepatic fat was quantified histologically and biochemically. Because flagellin challenge increased VAP-1 expression in human adipocytes, we used VAP-1 KO mice to determine whether VAP-1 regulates the inflammatory and metabolic effects of flagellin in vivo. In mice, VAP-1 mediated flagellin-induced inflammation, leukocyte infiltration, and lipolysis in visceral adipose tissue. Consequently, an increased release of glycerol led to hepatic steatosis in WT, but not in KO mice. Flagellin-induced hepatic fibrosis was not mediated by VAP-1. VAP-1 KO mice harbored more inflammation-related microbes than WT mice, while flagellin did not affect the gut microbiota. Our results suggest that by acting on visceral adipose tissue, flagellin increased leukocyte infiltration that induced lipolysis. Further, the released glycerol participated in hepatic fat accumulation. In conclusion, the results describe that gut microbial flagellin through VAP-1 induced hepatic steatosis. View Full-Text
Keywords: gut microbiota; liver; metabolism; inflammation gut microbiota; liver; metabolism; inflammation
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MDPI and ACS Style

Toivonen, R.; Vanhatalo, S.; Hollmén, M.; Munukka, E.; Keskitalo, A.; Pietilä, S.; Elo, L.; Huovinen, P.; Jalkanen, S.; Pekkala, S. Vascular Adhesion Protein 1 Mediates Gut Microbial Flagellin-Induced Inflammation, Leukocyte Infiltration, and Hepatic Steatosis. Sci 2021, 3, 13. https://doi.org/10.3390/sci3010013

AMA Style

Toivonen R, Vanhatalo S, Hollmén M, Munukka E, Keskitalo A, Pietilä S, Elo L, Huovinen P, Jalkanen S, Pekkala S. Vascular Adhesion Protein 1 Mediates Gut Microbial Flagellin-Induced Inflammation, Leukocyte Infiltration, and Hepatic Steatosis. Sci. 2021; 3(1):13. https://doi.org/10.3390/sci3010013

Chicago/Turabian Style

Toivonen, Raine, Sanja Vanhatalo, Maija Hollmén, Eveliina Munukka, Anniina Keskitalo, Sami Pietilä, Laura Elo, Pentti Huovinen, Sirpa Jalkanen, and Satu Pekkala. 2021. "Vascular Adhesion Protein 1 Mediates Gut Microbial Flagellin-Induced Inflammation, Leukocyte Infiltration, and Hepatic Steatosis" Sci 3, no. 1: 13. https://doi.org/10.3390/sci3010013

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