title: Intrahepatic cholesterol influences progression, inhibition and reversal of non-alcoholic steatohepatitis in hyperlipidemic mice.
abstract: Hepatic inflammation is the key factor in non-alcoholic steatohepatitis (NASH) and promotes progression to liver damage. We recently identified dietary cholesterol as the cause of hepatic inflammation in hyperlipidemic mice. We now show that hepatic transcriptome responses are strongly dependent on cholesterol metabolism during diet-induced NASH and its inhibition by fenofibrate. Furthermore, we show that, despite doubling hepatic steatosis, pharmacological LXR activation reverses hepatic inflammation, in parallel with reversing hepatic cholesterol levels. Together, the results indicate a prominent role of cholesterol during the development, inhibition and reversal of hepatic inflammation in NASH and reveal potential new therapeutic strategies against NASH.
authors.affiliation: Department of Molecular Genetics, Institutes of Maastricht University Maastricht, Maastricht, The Netherlands. kristiaan.wouters@inserm.fr
authors.forename: Kristiaan
authors.initials: K
authors.lastname: Wouters
authors.forename: Marc
authors.initials: M
authors.lastname: van Bilsen
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: van Gorp
authors.forename: Veerle
authors.initials: V
authors.lastname: Bieghs
authors.forename: Dieter
authors.initials: D
authors.lastname: Lütjohann
authors.forename: Anja
authors.initials: A
authors.lastname: Kerksiek
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.forename: Marten H
authors.initials: MH
authors.lastname: Hofker
authors.forename: Ronit
authors.initials: R
authors.lastname: Shiri-Sverdlov
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D004041:Dietary Fats / Q000009:adverse effects*; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008817:Mice, Mutant Strains
chemical_list: D004041:Dietary Fats; D002784:Cholesterol