PLoS ONE (Jan 2012)

Correction of liver steatosis by a hydrophobic iminosugar modulating glycosphingolipids metabolism.

  • Elisa Lombardo,
  • Cindy P A A van Roomen,
  • Gijs H van Puijvelde,
  • Roelof Ottenhoff,
  • Marco van Eijk,
  • Jan Aten,
  • Johan Kuiper,
  • Herman S Overkleeft,
  • Albert K Groen,
  • Arthur J Verhoeven,
  • Johannes M F G Aerts,
  • Florence Bietrix

DOI
https://doi.org/10.1371/journal.pone.0038520
Journal volume & issue
Vol. 7, no. 10
p. e38520

Abstract

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The iminosugar N-(5'-adamantane-1'-yl-methoxy)-pentyl-1-deoxynoijirimycin (AMP-DNM), an inhibitor of glycosphingolipid (GSL) biosynthesis is known to ameliorate diabetes, insulin sensitivity and to prevent liver steatosis in ob/ob mice. Thus far the effect of GSL synthesis inhibition on pre-existing NASH has not yet been assessed. To investigate it, LDLR(-/-) mice were kept on a western-type diet for 12 weeks to induce NASH. Next, the diet was continued for 6 weeks in presence or not of AMP-DNM in the diet. AMP-DNM treated mice showed less liver steatosis, inflammation and fibrosis. Induction of fatty acid beta-oxydation was observed, as well as a reduction of plasma lipids. Our study demonstrates that AMP-DNM treatment is able to significantly correct pre-existing NASH, suggesting that inhibiting GSL synthesis may represent a novel strategy for the treatment of this pathology.