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dc.contributor.authorMunukka, Eveliina
dc.contributor.authorWiklund, Petri
dc.contributor.authorPartanen, Tiina
dc.contributor.authorVälimäki, Sakari
dc.contributor.authorLaakkonen, Eija
dc.contributor.authorLehti, Maarit
dc.contributor.authorFischer-Posovzsky, Pamela
dc.contributor.authorWabitsch, Martin
dc.contributor.authorCheng, Sulin
dc.contributor.authorHuovinen, Pentti
dc.contributor.authorPekkala, Satu
dc.identifier.citationMunukka, E., Wiklund, P., Partanen, T., Välimäki, S., Laakkonen, E., Lehti, M., . . . Pekkala, S. (2016). Adipocytes as a Link Between Gut Microbiota-Derived Flagellin and Hepatocyte Fat Accumulation. <em>PLoS ONE</em>, 11 (4), e0152786. <a href="">doi:10.1371/journal.pone.0152786</a>
dc.description.abstractWhile the role of both elevated levels of circulating bacterial cell wall components and adipose tissue in hepatic fat accumulation has been recognized, it has not been considered that the bacterial components-recognizing adipose tissue receptors contribute to the hepatic fat content. In this study we found that the expression of adipose tissue bacterial flagellin (FLG)-recognizing Toll-like receptor (TLR) 5 associated with liver fat content (r = 0.699, p = 0.003) and insulin sensitivity (r = -0.529, p = 0.016) in humans (n = 23). No such associations were found for lipopolysaccharides (LPS)-recognizing TLR4. To study the underlying molecular mechanisms of these associations, human HepG2 hepatoma cells were exposed in vitro to the conditioned culture media derived from FLG or LPS-challenged human adipocytes. The adipocyte-mediated effects were also compared to the effects of direct HepG2 exposure to FLG and LPS. We found that the media derived from FLG-treated adipocytes stimulated fat accumulation in HepG2 cells, whereas either media derived from LPS-treated adipocytes or direct FLG or LPS exposure did not. This is likely due to that FLG-treatment of adipocytes increased lipolysis and secretion of glycerol, which is known to serve a substrate for triglyceride synthesis in hepatocytes. Similarly, only FLG-media significantly decreased insulin signaling-related Akt phosphorylation, IRS1 expression and mitochondrial respiratory chain ATP5A. In conclusion, our results suggest that the FLG-induced TLR5 activation in adipocytes increases glycerol secretion from adipocytes and decreases insulin signaling and mitochondrial functions, and increases fat accumulation in hepatocytes. These mechanisms could, at least partly, explain the adipose tissue TLR5 expression associated with liver fat content in humans.
dc.publisherPublic Library of Science
dc.relation.ispartofseriesPLoS ONE
dc.rightsCC BY 4.0
dc.subject.otheradipose tissue
dc.subject.otherhepatic fat
dc.subject.otherliver fat
dc.subject.otherfat accumulation
dc.subject.otherbacterial components
dc.subject.othertoll-like receptors
dc.subject.otherinsuline sensitivity
dc.titleAdipocytes as a Link Between Gut Microbiota-Derived Flagellin and Hepatocyte Fat Accumulation
dc.contributor.laitosTerveystieteiden laitosfi
dc.contributor.laitosDepartment of Health Sciencesen
dc.contributor.oppiaineGerontologia ja kansanterveys
dc.type.coarjournal article
dc.rights.copyright© 2016 Munukka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License.

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