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://ucrisportal.univie.ac.at/de/publications/84d9f82f-f05c-4a01-8443-7f36b98c6eb5