A1 Journal article (refereed)
Vascular Adhesion Protein 1 Mediates Gut Microbial Flagellin-Induced Inflammation, Leukocyte Infiltration, and Hepatic Steatosis (2021)

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

JYU authors or editors

Pekkala, Satu

Publication details

All authors or editors: Toivonen, Raine; Vanhatalo, Sanja; Hollmén, Maija; Munukka, Eveliina; Keskitalo, Anniina; Pietilä, Sami; Elo, Laura; Huovinen, Pentti; Jalkanen, Sirpa; Pekkala, Satu

Journal or series: Sci

eISSN: 2413-4155

Publication year: 2021

Volume: 3

Issue number: 1

Article number: 13

Publisher: MDPI

Place of Publication: Basel

Publication country: Switzerland

Publication language: English

DOI: https://doi.org/10.3390/sci3010013

Publication open access: Openly available

Publication channel open access: Open Access channel

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/74330

Web address of parallel published publication (pre-print): https://www.preprints.org/manuscript/202011.0097/v1

Abstract

Toll-like receptor 5 ligand, flagellin, and Vascular Adhesion Protein-1 (VAP-1) are involved in non-alcoholic fatty liver disease (NAFLD). 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 to C57BL/6J WT and C57BL/6-Aoc3-/- (VAP-1 KO) mice on high-fat diet twice a week every two 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, increased release of glycerol led to hepatic steatosis in WT but not KO mice. Flagellin-induced hepatic fibrosis was not mediated by VAP-1. VAP-1 KO mice harbored more inflammation-related microbes than WT, 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.

Keywords: gastrointestinal microbiota; liver; metabolism; inflammation

Free keywords: gut microbiota; liver; metabolism; inflammation

Fields of science: