Wordprocessing

Molecular Interactions between NAFLD and Xenobiotic Metabolism

Abstract:

Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, is a complex multifactorial disease characterized by metabolic deregulations that include accumulation of lipids in the liver, lipotoxicity, and insulin resistance. The progression of NAFLD to non-alcoholic steatohepatitis and cirrhosis, and ultimately to carcinomas, is governed by interplay of pro-inflammatory pathways, oxidative stress, as well as fibrogenic and apoptotic cues. As the liver is the major organ of biotransformation, deregulations in hepatic signaling pathways have effects on both, xenobiotic and endobiotic metabolism. Several major nuclear receptors involved in the transcription and regulation of phase I and II drug metabolizing enzymes and transporters also have endobiotic ligands including several lipids. Hence, hepatic lipid accumulation in steatosis and NAFLD, which leads to deregulated activation patterns of nuclear receptors, may result in altered drug metabolism capacity in NAFLD patients. On the other hand, genetic and association studies have indicated that a malfunction in drug metabolism can affect the prevalence and severity of NAFLD. This review focuses on the complex interplay between NAFLD pathogenesis and drug metabolism. A better understanding of these relationships is a prerequisite for developing improved drug dosing algorithms for the pharmacotherapy of patients with different stages of NAFLD.

23346097

Projects: A1.2: Detoxification in hepatocytes challenged by steatotic conditions, A3.4: Linking signalling to metabolic functions, A3.6: Transcription factor network and links to metabolism in NAFLD, G1: Clinical Translation to Invasively Characterized Patients, Showcase Steatosis

Front Genet
Front Genet 4: 2
22nd Jan 2013

Adviti Naik, Aleš Belič, Ulrich M Zanger, Damjana Rozman

help Authors

[Ulrich Zanger]

help Attributions

None

help Scales


Not Specified
Views: 1710
  • Created: 8th Jan 2014 at 14:35

Related items

Ajax-loader-large

Log in / Register

Need an account?
Sign up

Forgotten password?

Front Page

Virtual Liver Network

(v.0.22.0)

Related Projects and friends


Imprint Taverna workflow workbench myExperiment JWS Online ISATAB myGrid Sabio-RK BioPortal Semantic SBML

Powered by:

Ror-logo-32

Icons:
Silk icons 1.3
Crystal Clear icons