Hepatic gene expression profile associated with non-alcoholic steatohepatitis protection by S-nitroso-N-acetylcysteine in ob/ob mice.
OBJECTIVE
To understand the molecular mechanisms underlying non-alcoholic steatohepatitis (NASH) prevention by S-nitroso-N-acetylcysteine (SNAC), an NO donor that inhibits lipid peroxidation, we examined hepatic differentially expressed genes between ob/ob mice receiving or not SNAC treatment concomitantly with a methionine-choline deficient (MCD) diet.


METHODS
Ob/ob mice were assigned to receive oral SNAC fed solution (MCD+SNAC group) or vehicle (MCD group) by gavage. After four weeks, histopathological analysis and microarray hybridizations were conducted in liver tissues from groups. GeneSifter system was used to identify differentially expressed genes and pathways according to Gene Ontology.


RESULTS
NASH was absent in the MCD+SNAC group and no significant changes in food intake or body weight were observed in comparison to MCD group. After SNAC treatment, several genes belonging to oxidative phosphorylation, fatty acid biosynthesis, fatty acid metabolism and glutathione metabolism pathways were down-regulated in comparison to the MCD group.


CONCLUSIONS
SNAC treatment promotes down regulation of several genes from fatty acid (FA) metabolism related pathways, possibly through abrogation of the cytotoxic effects of reactive oxygen species and lipid peroxides with consequent prevention of mitochondrial overload. Further studies are required to investigate the clinical implications of these findings, in attempt to develop novel therapeutic strategies for NAFLD treatment.
de Oliveira
Claudia Pinto Marques Souza
CP
University of São Paulo School of Medicine, Department of Gastroenterology, São Paulo (SP), Brazil. cpm@usp.br
Stefano
José Tadeu
JT
de Lima
Vicência Mara Rodrigues
VM
de Sá
Sandra Valéria
SV
Simplicio
Fernanda Ibanez
FI
de Mello
Evandro Sobrosa
ES
Corrêa-Giannella
Maria Lúcia
ML
Alves
Venâncio Avancini Ferreira
VA
Laurindo
Francisco Rafael Martins
FR
de Oliveira
Marcelo Ganzarolli
MG
Giannella-Neto
Daniel
D
Carrilho
Flair José
FJ
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002796:Choline Deficiency / Q000188:drug therapy; D015536:Down-Regulation; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control*; D020869:Gene Expression Profiling / Q000379:methods; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D051379:Mice; D023421:Models, Animal; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D017382:Reactive Oxygen Species; D015854:Up-Regulation
D000975:Antioxidants; D005227:Fatty Acids; D017382:Reactive Oxygen Species; C024940:S-nitroso-N-acetylcysteine; D000111:Acetylcysteine