TY - JOUR
T1 - Correction of Liver Steatosis by a Hydrophobic Iminosugar Modulating Glycosphingolipids Metabolism
AU - Lombardo, Elisa
AU - van Roomen, Cindy P. A. A.
AU - van Puijvelde, Gijs H.
AU - Ottenhoff, Roelof
AU - van Eijk, Marco
AU - Aten, Jan
AU - Kuiper, Johan
AU - Overkleeft, Herman S.
AU - Groen, Albert K.
AU - Verhoeven, Arthur J.
AU - Aerts, Johannes M. F. G.
AU - Bietrix, Florence
PY - 2012
Y1 - 2012
N2 - 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
AB - 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
U2 - https://doi.org/10.1371/journal.pone.0038520
DO - https://doi.org/10.1371/journal.pone.0038520
M3 - Article
C2 - 23056165
SN - 1932-6203
VL - 7
SP - e38520-(10 p.)
JO - PLOS ONE
JF - PLOS ONE
IS - 10
ER -