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

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 pr...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b4de28f60b924b2b844fb54d2c4ccfb1
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spelling	oai:doaj.org-article:b4de28f60b924b2b844fb54d2c4ccfb12021-11-18T08:12:59ZCorrection of liver steatosis by a hydrophobic iminosugar modulating glycosphingolipids metabolism.1932-620310.1371/journal.pone.0038520https://doaj.org/article/b4de28f60b924b2b844fb54d2c4ccfb12012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23056165/?tool=EBIhttps://doaj.org/toc/1932-6203The 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.Elisa LombardoCindy P A A van RoomenGijs H van PuijveldeRoelof OttenhoffMarco van EijkJan AtenJohan KuiperHerman S OverkleeftAlbert K GroenArthur J VerhoevenJohannes M F G AertsFlorence BietrixPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 10, p e38520 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 Correction of liver steatosis by a hydrophobic iminosugar modulating glycosphingolipids metabolism.
description	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.
format	article
author	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
author_facet	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
author_sort	Elisa Lombardo
title	Correction of liver steatosis by a hydrophobic iminosugar modulating glycosphingolipids metabolism.
title_short	Correction of liver steatosis by a hydrophobic iminosugar modulating glycosphingolipids metabolism.
title_full	Correction of liver steatosis by a hydrophobic iminosugar modulating glycosphingolipids metabolism.
title_fullStr	Correction of liver steatosis by a hydrophobic iminosugar modulating glycosphingolipids metabolism.
title_full_unstemmed	Correction of liver steatosis by a hydrophobic iminosugar modulating glycosphingolipids metabolism.
title_sort	correction of liver steatosis by a hydrophobic iminosugar modulating glycosphingolipids metabolism.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/b4de28f60b924b2b844fb54d2c4ccfb1
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Correction of liver steatosis by a hydrophobic iminosugar modulating glycosphingolipids metabolism.

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