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

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  • Additional Information
    • Source:
      Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901227 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1547 (Electronic) Linking ISSN: 01931857 NLM ISO Abbreviation: Am J Physiol Gastrointest Liver Physiol Subsets: MEDLINE
    • Publication Information:
      Original Publication: Bethesda, MD : American Physiological Society
    • Subject Terms:
      Aging*; Acute-Phase Proteins/*metabolism ; Carrier Proteins/*metabolism ; Endotoxins/*blood ; Liver/*pathology ; Liver Cirrhosis/*pathology ; Membrane Glycoproteins/*metabolism; Acute-Phase Proteins/genetics ; Animals ; Apoptosis ; Biomarkers ; Carrier Proteins/genetics ; Female ; Gene Expression Regulation ; Glucose/metabolism ; Inflammation/pathology ; Insulin Receptor Substrate Proteins/genetics ; Insulin Receptor Substrate Proteins/metabolism ; Liver/metabolism ; Malate Dehydrogenase/genetics ; Malate Dehydrogenase/metabolism ; Male ; Membrane Glycoproteins/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; RNA, Messenger ; Receptor, Insulin/genetics ; Receptor, Insulin/metabolism ; Toll-Like Receptor 4/genetics ; Toll-Like Receptor 4/metabolism
    • Abstract:
      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.
    • Contributed Indexing:
      Keywords: Tlr-4 signaling; aging; bacterial endotoxin; lipopolysaccharide binding protein; liver degeneration
    • Accession Number:
      0 (Acute-Phase Proteins)
      0 (Biomarkers)
      0 (Carrier Proteins)
      0 (Endotoxins)
      0 (Insulin Receptor Substrate Proteins)
      0 (Irs1 protein, mouse)
      0 (Membrane Glycoproteins)
      0 (RNA, Messenger)
      0 (Tlr4 protein, mouse)
      0 (Toll-Like Receptor 4)
      0 (lipopolysaccharide-binding protein)
      EC 1.1.1.37 (Malate Dehydrogenase)
      EC 2.7.10.1 (Receptor, Insulin)
      IY9XDZ35W2 (Glucose)
    • Publication Date:
      Date Created: 20200225 Date Completed: 20200724 Latest Revision: 20200724
    • Publication Date:
      20221213
    • Accession Number:
      10.1152/ajpgi.00345.2018
    • Accession Number:
      32090603