Premium
Metabolomic tissue signature in human non‐alcoholic fatty liver disease identifies protective candidate metabolites
Author(s) -
Schönfels Witigo,
Patsenker Eleonora,
Fahrner René,
Itzel Timo,
Hinrichsen Holger,
Brosch Mario,
Erhart Wiebke,
Gruodyte Auste,
Vollnberg Bernd,
Richter Klaus,
Landrock Andreas,
Schreiber Stefan,
Brückner Stephan,
Beldi Guido,
Sipos Bence,
Becker Thomas,
Röcken Christoph,
Teufel Andreas,
Stickel Felix,
Schafmayer Clemens,
Hampe Jochen
Publication year - 2015
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12476
Subject(s) - steatohepatitis , fatty liver , metabolomics , steatosis , metabolite , medicine , biology , liver disease , disease , bioinformatics
Background Non‐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. Methods Discovery ( 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 30 s in patients. 252 metabolites were assessed using GC / MS . Replicated metabolites were evaluated in a murine high‐fat diet model of NAFLD . Results In a two‐stage metabolic screening, hydroquinone ( HQ , p combined = 3.0 × 10 −4 ) and nicotinic acid ( NA , p combined = 3.9 × 10 −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. Conclusion This 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 .