von Schoenfels, Witigo and Patsenker, Eleonora and Fahrner, Rene and Itzel, Timo and Hinrichsen, Holger and Brosch, Mario and Erhart, Wiebke and Gruodyte, Auste and Vollnberg, Bernd and Richter, Klaus and Landrock, Andreas and Schreiber, Stefan and Brueckner, Stephan and Beldi, Guido and Sipos, Bence and Becker, Thomas and Roecken, Christoph and Teufel, Andreas and Stickel, Felix and Schafmayer, Clemens and Hampe, Jochen (2015) Metabolomic tissue signature in human non-alcoholic fatty liver disease identifies protective candidate metabolites. LIVER INTERNATIONAL, 35 (1). pp. 207-214. ISSN 1478-3223, 1478-3231
Full text not available from this repository. (Request a copy)Abstract
BackgroundNon-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in industrialized countries, yet its pathophysiology is incompletely understood. Small-molecule metabolite screens may offer new insights into disease mechanisms and reveal new treatment targets. MethodsDiscovery (N=33) and replication (N=66) of liver biopsies spanning the range from normal liver histology to non-alcoholic steatohepatitis (NASH) were ascertained ensuring rapid freezing under 30s in patients. 252 metabolites were assessed using GC/MS. Replicated metabolites were evaluated in a murine high-fat diet model of NAFLD. ResultsIn a two-stage metabolic screening, hydroquinone (HQ, p(combined)=3.0x10(-4)) and nicotinic acid (NA, p(combined)=3.9x10(-9)) were inversely correlated with histological NAFLD severity. A murine high-fat diet model of NAFLD demonstrated a protective effect of these two substances against NAFLD: Supplementation with 1% HQ reduced only liver steatosis, whereas 0.6% NA reduced both liver fat content and serum transaminase levels and induced a complex regulatory network of genes linked to NALFD pathogenesis in a global expression pathway analysis. Human nutritional intake of NA equivalent was also consistent with a protective effect of NA against NASH progression. ConclusionThis first small-molecular screen of human liver tissue identified two replicated protective metabolites. Either the use of NA or targeting its regulatory pathways might be explored to treat or prevent human NAFLD.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NICOTINIC-ACID; SUSTAINED-RELEASE; NIACIN; STEATOHEPATITIS; LIPOPROTEINS; VALIDATION; PROFILES; ALCOHOL; MICE; TRANSESTERIFICATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Aug 2019 08:52 |
| Last Modified: | 02 Aug 2019 08:52 |
| URI: | https://pred.uni-regensburg.de/id/eprint/6314 |
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