A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
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-tekijät tai -toimittajat

Pekkala, Satu

Julkaisun tiedot

Julkaisun kaikki tekijät tai toimittajat: Toivonen, Raine; Vanhatalo, Sanja; Hollmén, Maija; Munukka, Eveliina; Keskitalo, Anniina; Pietilä, Sami; Elo, Laura; Huovinen, Pentti; Jalkanen, Sirpa; Pekkala, Satu

Lehti tai sarja: Sci

eISSN: 2413-4155

Julkaisuvuosi: 2021

Volyymi: 3

Lehden numero: 1

Artikkelinumero: 13

Kustantaja: MDPI

Kustannuspaikka: Basel

Julkaisumaa: Sveitsi

Julkaisun kieli: englanti

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

Julkaisun avoin saatavuus: Avoimesti saatavilla

Julkaisukanavan avoin saatavuus: Kokonaan avoin julkaisukanava

Julkaisu on rinnakkaistallennettu (JYX): https://jyx.jyu.fi/handle/123456789/74330

Rinnakkaistallenteen verkko-osoite (pre-print): https://www.preprints.org/manuscript/202011.0097/v1

Tiivistelmä

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.

YSO-asiasanat: suolistomikrobisto; maksa; aineenvaihdunta; tulehdus

Vapaat asiasanat: gut microbiota; liver; metabolism; inflammation

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