Aging-related liver degeneration is associated with increased bacterial endotoxin and lipopolysaccharide binding protein levels

Autor(en)
Cheng Jun Jin, Anja Baumann, Annette Brandt, Anna Engstler, Anika Nier, Marianne Hege, Christian Schmeer, Richard Kehm, Annika Höhn, Tilman Grune, Otto W. Witte, Ina Bergheim
Abstrakt

Aging is a risk factor in the development of many diseases, including liver-related diseases. The two aims of the present study were 1) to determine how aging affects liver health in mice in the absence of any interventions and 2) if degenerations observed in relation to blood endotoxin levels are critical in aging-associated liver degeneration. Endotoxin levels and markers of liver damage, mitochondrial dysfunction, insulin resistance, and apoptosis as well as the Toll-like receptor 4 (Tlr-4) signaling cascade were studied in liver tissue and blood, respectively, of 3- and 24-mo-old male C57BL/6J mice. In a second set of experiments, 3- to 4-mo-old and 14-mo-old female lipopolysaccharide- binding protein (LBP)-/- mice and littermates fed standard chow, markers of liver damage, insulin resistance, and mitochondrial dysfunction were assessed. Plasma activity of aspartate aminotransferase and histological signs of hepatic inflammation and fibrosis were significantly higher in old C57BL/6J mice than in young animals. The number of neutrophils, CD8α-positive cells, and mRNA expression of markers of apoptosis were also significantly higher in livers of old C57BL/6J mice compared with young animals, being also associated with a significant induction of hepatic Tlr-4 and LBP expression as well as higher endotoxin levels in peripheral blood. Compared with age-matched littermates, LBP-/- mice display less signs of senescence in liver. Taken together, our data suggest that, despite being fed standard chow, old mice developed liver inflammation and beginning fibrosis and that bacterial endotoxin may play a critical role herein.

Organisation(en)
Department für Ernährungswissenschaften
Externe Organisation(en)
Friedrich-Schiller-Universität Jena, Heinrich-Heine-Universität Düsseldorf, Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DIfE), Universitätsklinikum Jena, Deutsches Zentrum für Diabetesforschung
Journal
American journal of physiology. Gastrointestinal and liver physiology
Band
318
Seiten
G736-G747
Anzahl der Seiten
12
ISSN
0193-1857
DOI
https://doi.org/10.1152/ajpgi.00345.2018
Publikationsdatum
04-2020
Peer-reviewed
Ja
ÖFOS 2012
303009 Ernährungswissenschaften
Schlagwörter
ASJC Scopus Sachgebiete
Gastroenterology, Physiology (medical), Physiology, Hepatology
Link zum Portal
https://ucris.univie.ac.at/portal/de/publications/agingrelated-liver-degeneration-is-associated-with-increased-bacterial-endotoxin-and-lipopolysaccharide-binding-protein-levels(84d9f82f-f05c-4a01-8443-7f36b98c6eb5).html