Gene expression in human NAFLD.
Despite the high prevalence of nonalcoholic fatty liver disease (NAFLD), little is known of its pathogenesis based on study of human liver samples. By the use of Affymetrix GeneChips (17,601 genes), we investigated gene expression in the human liver of subjects with extreme steatosis due to NAFLD without histological signs of inflammation (liver fat 66.0 +/- 6.8%) and in subjects with low liver fat content (6.4 +/- 2.7%). The data were analyzed by using sequence-based reannotation of Affymetrix probes and a robust model-based normalization method. We identified genes involved in hepatic glucose and lipid metabolism, insulin signaling, inflammation, coagulation, and cell adhesion to be significantly associated with liver fat content. In addition, genes involved in ceramide signaling (MAP2K4) and metabolism (UGCG) were found to be positively associated with liver fat content. Genes involved in lipid metabolism (PLIN, ACADM), fatty acid transport (FABP4, CD36), amino acid catabolism (BCAT1), and inflammation (CCL2) were validated by real-time PCR and were found to be upregulated in subjects with high liver fat content. The data show that multiple changes in gene expression characterize simple steatosis.
Greco
Dario
D
Institute of Biotechnology, University of Helsinki, Finland.
Kotronen
Anna
A
Westerbacka
Jukka
J
Puig
Oscar
O
Arkkila
Perttu
P
Kiviluoto
Tuula
T
Laitinen
Saara
S
Kolak
Maria
M
Fisher
Rachel M
RM
Hamsten
Anders
A
Auvinen
Petri
P
Yki-Järvinen
Hannele
H
D042964:Acyl-CoA Dehydrogenase / Q000235:genetics; D000328:Adult; D018955:CD36 Antigens / Q000235:genetics; D050260:Carbohydrate Metabolism / Q000235:genetics; D002352:Carrier Proteins; D018932:Chemokine CCL2 / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D005234:Fatty Liver / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000637:Transaminases / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
C111835:CCL2 protein, human; D018955:CD36 Antigens; D002352:Carrier Proteins; D018932:Chemokine CCL2; D016326:Extracellular Matrix Proteins; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000070778:Perilipin-1; D010750:Phosphoproteins; D042964:Acyl-CoA Dehydrogenase; C490590:BCAT1 protein, human; D000637:Transaminases