Aging-related liver degeneration is associated with increased bacterial endotoxin and lipopolysaccharide binding protein levels
| العنوان: | Aging-related liver degeneration is associated with increased bacterial endotoxin and lipopolysaccharide binding protein levels |
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| المؤلفون: | Marianne Hege, Anna Janina Engstler, Annika Höhn, Richard Kehm, Cheng Jun Jin, Otto W. Witte, Annette Brandt, Anika Nier, Christian Schmeer, Anja Baumann, Ina Bergheim, Tilman Grune |
| المصدر: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 318:G736-G747 |
| بيانات النشر: | American Physiological Society, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Liver Cirrhosis, Male, Senescence, Aging, medicine.medical_specialty, Physiology, Apoptosis, Inflammation, Mice, Insulin resistance, Malate Dehydrogenase, Fibrosis, Physiology (medical), Internal medicine, Animals, Medicine, RNA, Messenger, Risk factor, Receptor, Mice, Knockout, Membrane Glycoproteins, Hepatology, biology, business.industry, Gastroenterology, medicine.disease, Receptor, Insulin, Endotoxins, Mice, Inbred C57BL, Toll-Like Receptor 4, Glucose, Endocrinology, Gene Expression Regulation, Liver, Insulin Receptor Substrate Proteins, biology.protein, Female, medicine.symptom, Carrier Proteins, business, Lipopolysaccharide binding protein, Biomarkers, Acute-Phase Proteins |
| الوصف: | 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. NEW & NOTEWORTHY Old age in mice is associated with marked signs of liver degeneration, hepatic inflammation, and fibrosis. Aging-associated liver degeneration is associated with elevated bacterial endotoxin levels and an induction of lipopolysaccharide-binding protein (LBP) and Toll-like receptor 4-dependent signaling cascades in liver tissue. Furthermore, in old aged LBP−/− mice, markers of senescence seem to be lessened, supporting the hypothesis that bacterial endotoxin levels might be critical in aging-associated decline of liver. |
| تدمد: | 1522-1547 0193-1857 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::43e62c968c1bcd4e8f3dad45d8f458acTest https://doi.org/10.1152/ajpgi.00345.2018Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....43e62c968c1bcd4e8f3dad45d8f458ac |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221547 01931857 |
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