Gene expression in human NAFLD
Abstract
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.
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Hepatic CD36 expression is directly correlated with liver fat in human subjects.
“hepatic CD36 expression is directly correlated with liver fat in human subjects (29).”
From Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity (2009) · cites this paper as [29]
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Self-citation
- Authors
- Greco, D., Kotronen, A., Westerbacka, J., Puig, O., Arkkila, P., Kiviluoto, T., Laitinen, S., Kolak, M., Fisher, R. M., Hamsten, A., Auvinen, P., & Yki-Järvinen, H.
- Affiliations
- University of Helsinki (FI)
- Venue
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Publisher
- American Physiological Society
- Published
- 2008-05
- Volume
- 294
- Issue
- 5
- Pages
- G1281-G1287
- ISSN
- 0193-1857 (ISSN-L)
- 1522-1547
- OpenAlex
- W2114199165
- Cited by
- 427
- References
- 62
- Citations by year
- 2026: 13 · 2025: 17 · 2024: 20 · 2023: 28 · 2022: 26 · 2021: 34 · 2020: 30 · 2019: 22 · 2018: 26 · 2017: 21 · 2016: 25 · 2015: 20 · 2014: 27 · 2013: 25 · 2012: 16
- FWCI
- 19.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- non-alcoholic fatty liver disease, hepatic steatosis, gene expression, liver fat, hepatic lipid metabolism, hepatic glucose metabolism, insulin signaling, inflammation, coagulation, cell adhesion, ceramide signaling, fatty acid uptake, amino acid catabolism, MCP-1, FABP4, CD36, BCAT1
- MeSH terms
- Perilipin-1, Adult, Transaminases, Carrier Proteins, Fatty Liver, Female, Humans, Inflammation, Middle Aged, Phosphoproteins, Down-Regulation, Up-Regulation, Extracellular Matrix Proteins, Chemokine CCL2, CD36 Antigens, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Acyl-CoA Dehydrogenase, Intracellular Signaling Peptides and Proteins, Carbohydrate Metabolism, Lipid Metabolism, Fatty Acid-Binding Proteins
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