Aldehyde oxidase 1 is highly abundant in hepatic steatosis and is downregulated by adiponectin and fenofibric acid in hepatocytes in vitro

Journal Article · Fri Nov 24 04:00:00 EST 2006 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2006.09.101· OSTI ID:20854589

Neumeier, Markus ^[1]; Weigert, Johanna ^[1]; Schaeffler, Andreas ^[1]; Weiss, Thomas S ^[2]; Schmidl, Christian ^[1]; Buettner, Roland ^[1]; Bollheimer, Cornelius ^[1]; Aslanidis, Charalampos ^[3]; Schoelmerich, Juergen ^[1]; Buechler, Christa ^[1]

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1. Department of Internal Medicine I, University of Regensburg, D-93042 Regensburg (Germany)
2. Center for Liver Cell Research, University of Regensburg (Germany)
3. Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg (Germany)

Adiponectin protects the liver from steatosis caused by obesity or alcohol and therefore the influence of adiponectin on human hepatocytes was analyzed. GeneChip experiments indicated that recombinant adiponectin downregulates aldehyde oxidase 1 (AOX1) expression and this was confirmed by real-time RT-PCR and immunoblot. AOX1 is a xenobiotic metabolizing protein and produces reactive oxygen species (ROS), that promote cell damage and fibrogenesis. Adiponectin and fenofibric acid activate peroxisome proliferator-activated receptor-{alpha} (PPAR-{alpha}) and both suppress AOX1 protein and this is blocked by the PPAR-{alpha} antagonist RU486. Obesity is associated with low adiponectin, reduced hepatic PPAR-{alpha} activity and fatty liver, and AOX1 was found induced in the liver of rats on a high-fat diet when compared to controls. Free fatty acids and leptin, that are elevated in obesity, failed to upregulate AOX1 in vitro. The current data indicate that adiponectin reduces AOX1 by activating PPAR-{alpha} whereas fatty liver disease is associated with elevated hepatic AOX1. High AOX1 may be associated with higher ROS well described to induce fibrogenesis in liver tissue but may also influence drug metabolism and activity.

• OSTI ID: 20854589
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 350; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ALCOHOLS
ALDEHYDES
CARBOXYLIC ACIDS
DIET
DRUGS
FATS
IN VITRO
LEPTIN
LIVER
LIVER CELLS
METABOLIC DISEASES
METABOLISM
OXIDASES
POLYMERASE CHAIN REACTION
RATS
RECEPTORS